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André Kipnis
Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil

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Letter
Published: 26 October 2020 in Trials
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Objectives The BCG vaccine, widely used in Brazil in new-borns, induces adjuvant protection for several diseases, including childhood virus infections. BCG activates monocytes and innate memory NK cells which are crucial for the antiviral immune response. Therefore, strategies to prevent COVID-19 in health workers (HW) should be carried out to prevent them becoming unwell so that they can continue to work during the pandemic. The hypothesis is that BCG will improve the innate immune response and prevent symptomatic infection or COVID-19 severity. The primary objective is to verify the effectiveness and safety of the BCG vaccine to prevent or reduce incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the city of Goiânia (Brazil) among HW previously vaccinated with BCG and also its severity and mortality during the pandemic of the disease. Secondary objectives are to estimate the incidence of COVID-19 among these professionals and the innate immune response elicited to BCG. Trial design This a phase II trial for repositioning BCG as a preventive strategy against COVID-19. The trial is an open-label, parallel-group randomised clinical trial, comparing HW vaccinated with BCG and HW not vaccinated. Participants The trial will recruit 800 HW of Goiânia - Goiás, Brazil to reach a total of 400 HW included after comorbidities questioning and laboratorial evaluation. Eligibility criteria: Any HW presenting BCG vaccination scar with direct contact with suspected COVID-19 patients for at least 8 hours per week, whether in hospital beds, ICU, or in transportation or admission (nurses, doctors, physiotherapists, nutritionists, receptionists, etc.) who have negative IgM and IgG COVID-19 test. Participants with any of the following characteristics will be excluded: - Have had in the last fifteen days any signs or symptoms of virus infection, including COVID-19; - Have had fever in the last fifteen days; - Have been vaccinated fifteen days before the inclusion; - Have a history or confirmation of any immunosuppressive disease such as HIV, presented solid tumour in the last two years or autoimmune diseases; - Are under preventive medication with antibiotics, steroid anti-inflammatories, or chemotherapy; - Have less than 500 neutrophils per mL of blood; - Have previously been diagnosed with tuberculosis; - Are breastfeeding or pregnant; - Are younger than 18 years old; - Are participating as an investigator in this clinical trial. Intervention and comparator HW will be randomized into the BCG vaccinated group or the BCG unvaccinated control group. The BCG vaccinated group will receive in the right arm, intradermally, a one off dose of 0.1 mL corresponding to approximately 2 x105 to 8 x105 CFU of live, freeze-dried, attenuated BCG Moscow 361-I, Bacillus Calmette Guerin vaccine (Serum Institute of India PVT. LTD.). The unvaccinated control group will not be vaccinated. The HW allocated in both groups will be followed up at specific times points until 180 days post inclusion. The vaccinated and control groups will be compared according to COVID-19 related outcomes. Main outcomes The primary outcomes are the incidence coefficient of infection by SARS-CoV-2 determined by RT-PCR of naso-oropharyngeal swab specimen or rapid lateral flow IgG and IgM test, and presence of general COVID-19 symptoms, disease severity and admission to hospital during the 180 days of follow up. The secondary outcome is the innate immune response elicited 15-20 days after vaccination. Randomisation The vaccine vial contains approximately 10 doses. In order to optimize the vaccine use, the randomisation was performed in blocks of 20 participants using the platform randomization.com [http://www.jerrydallal.com/random/permute.htm]. The randomization was prepared before any HW inclusion. The results were printed and inserted in sealed envelopes that were numbered with BCG-001 to BCG-400. The printed results as well the envelopes had the same numbers. At the time of the randomisation, each participant that meets the inclusion criteria will receive a consecutive participant number [BCG-001-BCG-400]. The sealed envelope with the assigned number, blinded to the researchers, will be opened in front of the participant and the arm allocation will be known. Blinding (masking) There is no masking for the participants or for the healthcare providers. The study will be blinded to the laboratory researchers and to those who will be evaluating the outcomes and performing the statistical analyses. In this case, only the participant identification number will be available. Numbers to be randomised (sample size) Four hundred heath workers will be randomised in two groups. Two hundred participants will be vaccinated, and 200 participants will not be vaccinated. Trial Status The protocol approved by the Brazilian Ethical Committee is the seventh version, number CAAE: 31783720.0.0000.5078. The trial has been recruiting since September 20th, 2020. The clinical trial protocol was registered on August 5th, 2020. It is estimated that recruitment will finish by March 2021. Trial registration The protocol number was registered on August 5th, 2020 at REBEC (Registro Brasileiro de Ensaios Clínicos). Register number: RBR-4kjqtg and WHO trial registration number UTN: U1111-1256-3892. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

ACS Style

Ana Paula Junqueira-Kipnis; Laura Raniere Borges Dos Anjos; Lília Cristina De Souza Barbosa; Adeliane Castro Da Costa; Kellen Christina Malheiros Borges; Amanda Da Rocha Oliveira Cardoso; Kaio Mota Ribeiro; Sarah Brena Aparecida Rosa; Carine De Castro Souza; Rogério Coutinho Das Neves; Guylherme Saraiva; Sueli Meira Da Silva; Erika Aparecida Da Silveira; Marcelo Fouad Rabahi; Marcus Barreto Conte; André Kipnis. BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial. Trials 2020, 21, 1 -3.

AMA Style

Ana Paula Junqueira-Kipnis, Laura Raniere Borges Dos Anjos, Lília Cristina De Souza Barbosa, Adeliane Castro Da Costa, Kellen Christina Malheiros Borges, Amanda Da Rocha Oliveira Cardoso, Kaio Mota Ribeiro, Sarah Brena Aparecida Rosa, Carine De Castro Souza, Rogério Coutinho Das Neves, Guylherme Saraiva, Sueli Meira Da Silva, Erika Aparecida Da Silveira, Marcelo Fouad Rabahi, Marcus Barreto Conte, André Kipnis. BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020; 21 (1):1-3.

Chicago/Turabian Style

Ana Paula Junqueira-Kipnis; Laura Raniere Borges Dos Anjos; Lília Cristina De Souza Barbosa; Adeliane Castro Da Costa; Kellen Christina Malheiros Borges; Amanda Da Rocha Oliveira Cardoso; Kaio Mota Ribeiro; Sarah Brena Aparecida Rosa; Carine De Castro Souza; Rogério Coutinho Das Neves; Guylherme Saraiva; Sueli Meira Da Silva; Erika Aparecida Da Silveira; Marcelo Fouad Rabahi; Marcus Barreto Conte; André Kipnis. 2020. "BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial." Trials 21, no. 1: 1-3.

Original research article
Published: 22 April 2020 in Frontiers in Immunology
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It has been shown that neutrophils drive NK cells to activate DCs while NK cells regulate neutrophils survival. In response to mycobacteria, NK cells proliferate and produces IFN-γ, that appears to regulate the neutrophilic inflammatory responses to both M. tuberculosis infection and BCG vaccination. Although the role of neutrophils in the immune response to tuberculosis is a matter of debate, neutrophils were shown to be crucial to induce specific response against mc2-CMX vaccine. The objective of this study was to investigate the interplay between NK cells and neutrophils in regard to the development of a protective immune response against M. tuberculosis. Depletion of NK cells during vaccination did not alter the total number of neutrophils or DCs, but reduced the number of activated DCs, thus reducing the generation of Th1 specific immune responses and the protection conferred by mc2-CMX and BCG vaccines. However, only in mc2-CMX vaccination that neutrophil depletion interfered with the NK cell numbers and protection. In conclusion, it was shown that only when both NK and neutrophils were present, specific Th1 response and protection was achieved by mc2-CMX vaccine, while neutrophils although activated upon BCG vaccination were not necessary for the induced protection.

ACS Style

Ana Paula Junqueira-Kipnis; Monalisa Martins Trentini; Lázaro Moreira Marques Neto; Andre Kipnis. Live Vaccines Have Different NK Cells and Neutrophils Requirements for the Development of a Protective Immune Response Against Tuberculosis. Frontiers in Immunology 2020, 11, 741 .

AMA Style

Ana Paula Junqueira-Kipnis, Monalisa Martins Trentini, Lázaro Moreira Marques Neto, Andre Kipnis. Live Vaccines Have Different NK Cells and Neutrophils Requirements for the Development of a Protective Immune Response Against Tuberculosis. Frontiers in Immunology. 2020; 11 ():741.

Chicago/Turabian Style

Ana Paula Junqueira-Kipnis; Monalisa Martins Trentini; Lázaro Moreira Marques Neto; Andre Kipnis. 2020. "Live Vaccines Have Different NK Cells and Neutrophils Requirements for the Development of a Protective Immune Response Against Tuberculosis." Frontiers in Immunology 11, no. : 741.

Applied microbial and cell physiology
Published: 06 April 2020 in Applied Microbiology and Biotechnology
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Mycobacterium abscessus subsp. massiliense (Mycma) belongs to the Mycobacterium abscessus complex and is a rapidly growing non-tuberculous mycobacterium. The chronic pulmonary, skin, and soft tissue infections that it causes may be difficult to treat due to its intrinsic resistance to the commonly used antimicrobial drugs, making it a serious world public health problem. Iron is an essential nutrient for the growth of microorganisms; nonetheless, it can be toxic when in excess. Thus, bacteria require an iron homeostasis mechanism to succeed in different environments. DNA-binding proteins from starved cells (Dps) are miniferritins with the property to act as additional iron storage proteins but also can bind to DNA, protecting it against hydroxyl radical. Annotation of the Mycma genome revealed the gene mycma_03135 with 79% sequential identity when compared to MSMEG_3242 gene from M. smegmatis mc2 155, which codifies for a known Dps. Recombinant Dps from M. abscessus (rMaDps) was produced in Escherichia coli, purified in soluble form and shown to form high mass oligomers in solution with ferroxidase activity, DNA binding, and protection against damage. The expression of the mycma_03135 gene was induced during Mycma growth in the presence of hydrogen peroxide (H2O2). Additionally, the expression of rMaDps by E. coli conferred greater resistance to H2O2. Thus, this study is the first to identify and characterize a Dps from M. abscessus. KEY POINTS: Mycobacterium abscessus subsp. massiliense express a miniferritin protein (Dps). Mycma Dps binds to DNA and protects against oxidative stress.

ACS Style

Nayra Rodrigues De Alcântara; Fábio Muniz de Oliveira; Wanius Garcia; Otavio Augusto Leitão Dos Santos; Ana Paula Junqueira-Kipnis; André Kipnis. Dps protein is related to resistance of Mycobacterium abscessus subsp. massiliense against stressful conditions. Applied Microbiology and Biotechnology 2020, 104, 5065 -5080.

AMA Style

Nayra Rodrigues De Alcântara, Fábio Muniz de Oliveira, Wanius Garcia, Otavio Augusto Leitão Dos Santos, Ana Paula Junqueira-Kipnis, André Kipnis. Dps protein is related to resistance of Mycobacterium abscessus subsp. massiliense against stressful conditions. Applied Microbiology and Biotechnology. 2020; 104 (11):5065-5080.

Chicago/Turabian Style

Nayra Rodrigues De Alcântara; Fábio Muniz de Oliveira; Wanius Garcia; Otavio Augusto Leitão Dos Santos; Ana Paula Junqueira-Kipnis; André Kipnis. 2020. "Dps protein is related to resistance of Mycobacterium abscessus subsp. massiliense against stressful conditions." Applied Microbiology and Biotechnology 104, no. 11: 5065-5080.

Original article
Published: 23 January 2020 in Journal of Applied Microbiology
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Aims The importance of bacterioferritin in the virulence and pathogenicity of the genus Mycobacterium is still unclear. The aim of this study was to analyze if the expression of a recombinant bacterioferritin from M. tuberculosis (Mtb) by Mycma could improve the capacity of this bacillus to resist the host defense mechanisms. Methods and Results Recombinant Mycma, expressing bacterioferritin (Rv1876) from Mtb, was developed by transformation with pMIP12_Rv1876. To determine bacterioferritin influence on Mycma physiology and virulence, the mycobacteria growth was analyzed in vitro and in vivo. It was observed that the expression of bacterioferritin improved the growth rate of recombinant Mycma_BfrA under iron excess and oxidative stress, as compared to the wild type. Furthermore, in the murine model of infection, it was observed that Mycma_BfrA‐infected mice had higher bacillary load and a more pronounced lesion in the lungs when compared to the wild type. Conclusion This study showed that bacterioferritin confers additional resistance to stress conditions, resulting in increased pathogenicity of Mycma during mice infection. Significance and Impact of Study This study provides new insights about the importance of bacterioferritin in the virulence and pathogenicity of the Mycobacterium genus.

ACS Style

F.M. Oliveira; F.V. Marinho; S.C. Oliveira; D.P. Resende; Ana Paula Junqueira Kipnis. Mycobacterium abscessus subsp. massiliense expressing bacterioferritin have improved resistance to stressful conditions. Journal of Applied Microbiology 2020, 128, 1802 -1813.

AMA Style

F.M. Oliveira, F.V. Marinho, S.C. Oliveira, D.P. Resende, Ana Paula Junqueira Kipnis. Mycobacterium abscessus subsp. massiliense expressing bacterioferritin have improved resistance to stressful conditions. Journal of Applied Microbiology. 2020; 128 (6):1802-1813.

Chicago/Turabian Style

F.M. Oliveira; F.V. Marinho; S.C. Oliveira; D.P. Resende; Ana Paula Junqueira Kipnis. 2020. "Mycobacterium abscessus subsp. massiliense expressing bacterioferritin have improved resistance to stressful conditions." Journal of Applied Microbiology 128, no. 6: 1802-1813.

Journal article
Published: 04 November 2019 in Revista de Patologia Tropical / Journal of Tropical Pathology
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Medicinal plants are of great interest for the discovery of new biomolecules with diversified effects. Over the last decade different outbreaks caused by Mycobacterium abscessus subsp. massiliense have been reported, evidencing it as an important emerging pathogen in underdeveloped countries. This study investigated the antimycobacterial activity of six Brazilian medicinal plant extracts and their fractions. Hyptis brevipes, Tocoyena formosa, Randia armata, Paullinia pinnata, Lafoensia pacari and Anadenanthera colubrina were evaluated against M. a. massiliense. Total extracts from the medicinal plants H. brevipes, T. formosa, P. pinnata and L. pacari presented a minimal bactericidal concentration of 1 mg/mL. After fractioning, the ethanolic fractions from H. brevipes and P. pinnata presented bactericidal activity, and the ethyl acetate fraction from H. brevipes and T. formosa presented antimycobacterial action. The best bactericidal function of all plant fractions was the ethanolic, which contained rutin and rosmarinic acid that were shown to have microbicidal activity. KEY WORDS: Mycobacterium abscessus; medicinal plants; Brazilian medicinal plants; HPLCand biodiversity.

ACS Style

Rogério Coutinho Das Neves; Rayanny Gomes Andrade; Carlos Alexandre Carollo; Amanda Galdi Boaretto; Andre Kipnis; Ana Paula Junqueira- Kipnis. Hyptis brevipes AND Paullinia pinnata EXTRACTS AND THEIR FRACTIONS PRESENTING ACTIVITY AGAINST Mycobacterium abscessus subsp. massiliense. Revista de Patologia Tropical / Journal of Tropical Pathology 2019, 48, 148 -160.

AMA Style

Rogério Coutinho Das Neves, Rayanny Gomes Andrade, Carlos Alexandre Carollo, Amanda Galdi Boaretto, Andre Kipnis, Ana Paula Junqueira- Kipnis. Hyptis brevipes AND Paullinia pinnata EXTRACTS AND THEIR FRACTIONS PRESENTING ACTIVITY AGAINST Mycobacterium abscessus subsp. massiliense. Revista de Patologia Tropical / Journal of Tropical Pathology. 2019; 48 (3):148-160.

Chicago/Turabian Style

Rogério Coutinho Das Neves; Rayanny Gomes Andrade; Carlos Alexandre Carollo; Amanda Galdi Boaretto; Andre Kipnis; Ana Paula Junqueira- Kipnis. 2019. "Hyptis brevipes AND Paullinia pinnata EXTRACTS AND THEIR FRACTIONS PRESENTING ACTIVITY AGAINST Mycobacterium abscessus subsp. massiliense." Revista de Patologia Tropical / Journal of Tropical Pathology 48, no. 3: 148-160.

Journal article
Published: 10 April 2019 in Revista de Patologia Tropical / Journal of Tropical Pathology
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Tuberculosis is a contagious infectious disease caused by Mycobacterium tuberculosis, an obligate intracellular bacterium that relies on infection and host to host transmission to survive. In a co-evolution process, the pathogen developed virulence mechanisms to evade the host’s immune system and endure many factors, such as cellular stress for example. One of the strategies used by pathogens to achieve success in their infection is the production of proteases, which are enzymes that cleave peptide bonds between the amino acids in a protein. Proteases are widely distributed in the nature and have different roles that are considered important to the bacteria biological cycle. M. tuberculosis have several protease coding genes in its genome, many of which with unknown function, but several with attributed role in the infection process. This review presents the literature searched between 2014 and 2018 that addressed the roles of the proteases involved in the Mycobacterium tuberculosis infection.

ACS Style

Rayanny Gomes De Andrade; Ana Paula Junqueira-Kipnis; Andre Kipnis. PROTEASES ASSOCIATED WITH Mycobacterium tuberculosis INFECTION. Revista de Patologia Tropical / Journal of Tropical Pathology 2019, 48, 1 -12.

AMA Style

Rayanny Gomes De Andrade, Ana Paula Junqueira-Kipnis, Andre Kipnis. PROTEASES ASSOCIATED WITH Mycobacterium tuberculosis INFECTION. Revista de Patologia Tropical / Journal of Tropical Pathology. 2019; 48 (1):1-12.

Chicago/Turabian Style

Rayanny Gomes De Andrade; Ana Paula Junqueira-Kipnis; Andre Kipnis. 2019. "PROTEASES ASSOCIATED WITH Mycobacterium tuberculosis INFECTION." Revista de Patologia Tropical / Journal of Tropical Pathology 48, no. 1: 1-12.

Journal article
Published: 10 April 2019 in Toxins
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Intravascular stent infection is a rare complication with a high morbidity and high mortality; bacteria from the hospital environment form biofilms and are often multidrug-resistant (MDR). Antimicrobial peptides (AMPs) have been considered as alternatives to bacterial infection treatment. We analyzed the formation of the bacterial biofilm on the vascular stents and also tested the inhibition of this biofilm by AMPs to be used as treatment or coating. Antimicrobial activity and antibiofilm were tested with wasp (Agelaia-MPI, Polybia-MPII, Polydim-I) and scorpion (Con10 and NDBP5.8) AMPs against Acinetobacter baumannii clinical strains. A. baumannii formed a biofilm on the vascular stent. Agelaia-MPI and Polybia-MPII inhibited biofilm formation with bacterial cell wall degradation. Coating biofilms with polyethylene glycol (PEG 400) and Agelaia-MPI reduced 90% of A. baumannii adhesion on stents. The wasp AMPs Agelaia-MPI and Polybia-MPII had better action against MDR A. baumannii adherence and biofilm formation on vascular stents, preventing its formation and treating mature biofilm when compared to the other tested peptides.

ACS Style

Rogério Coutinho Das Neves; Márcia Renata Mortari; Elisabeth Ferroni Schwartz; André Kipnis; Ana Paula Junqueira-Kipnis. Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii. Toxins 2019, 11, 216 .

AMA Style

Rogério Coutinho Das Neves, Márcia Renata Mortari, Elisabeth Ferroni Schwartz, André Kipnis, Ana Paula Junqueira-Kipnis. Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii. Toxins. 2019; 11 (4):216.

Chicago/Turabian Style

Rogério Coutinho Das Neves; Márcia Renata Mortari; Elisabeth Ferroni Schwartz; André Kipnis; Ana Paula Junqueira-Kipnis. 2019. "Antimicrobial and Antibiofilm Effects of Peptides from Venom of Social Wasp and Scorpion on Multidrug-Resistant Acinetobacter baumannii." Toxins 11, no. 4: 216.

Original research article
Published: 27 February 2019 in Indian Journal of Microbiology
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Iron (Fe) homeostasis control is important for both pathogen and the host. During infection, the host reduces the access of microorganisms to iron, however, studies have shown that virulent pathogens are capable to sequester Fe from host proteins, and establish the infection. M. abscessus subsp. massiliense (Mycma), that is resistant to most drugs used against tuberculosis, was responsible for outbreaks around the world showing increased virulence when compared to other rapidly growing mycobacteria. The goal of this study was to determine whether Mycma produce siderophores and if the mycma_1113 gene expression, a putative homolog of M. tuberculosis mbtB gene located in the mbt gene cluster, is related to the synthesis of these molecules. For that, the effect of different iron concentrations on the growth of Mycma, the expression of mycma_1113 gene, and the production of siderophores was evaluated in vitro and in vivo. It is shown that Mycma produce siderophores under iron deprivation conditions and mycma_1113 gene expression was influenced by iron availability. The mycma_1113 gene expression was also increased after macrophage or in vivo infection indicating that mycobactin synthesis by Mycma could participate in the Fe sequestration from the host during infection. In conclusion, we show that Mycma produces siderophores under iron deprivation conditions and that the mycma_1113 gene is involved in this process, furthermore, this gene expression is induced during infection.

ACS Style

Fábio Muniz de Oliveira; Viviane Lopes Rocha Corrêa; André França Corrêa; Adeliane Castro Da Costa; Victor Oliveira Procopio; Ana Paula Junqueira-Kipnis; André Kipnis. The mycma_1113 Gene from Mycobacterium abscessus subsp. massiliense is Related to Siderophore Synthesis. Indian Journal of Microbiology 2019, 59, 180 -187.

AMA Style

Fábio Muniz de Oliveira, Viviane Lopes Rocha Corrêa, André França Corrêa, Adeliane Castro Da Costa, Victor Oliveira Procopio, Ana Paula Junqueira-Kipnis, André Kipnis. The mycma_1113 Gene from Mycobacterium abscessus subsp. massiliense is Related to Siderophore Synthesis. Indian Journal of Microbiology. 2019; 59 (2):180-187.

Chicago/Turabian Style

Fábio Muniz de Oliveira; Viviane Lopes Rocha Corrêa; André França Corrêa; Adeliane Castro Da Costa; Victor Oliveira Procopio; Ana Paula Junqueira-Kipnis; André Kipnis. 2019. "The mycma_1113 Gene from Mycobacterium abscessus subsp. massiliense is Related to Siderophore Synthesis." Indian Journal of Microbiology 59, no. 2: 180-187.

Journal article
Published: 05 November 2018 in Tuberculosis
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Severe obesity and diabetes lead to a significant decrease in quality of life. Although controversial, population-wide studies have implicated obesity in the development of tuberculosis (TB). Non-classical monocytes have been described in obesity and TB, whereas in diabetes they have been associated with poorer clinical outcomes. The present study focuses on the functional significance of several monocyte populations of obese, obesity-related diabetic (OBDM), non-obese/diabetic tuberculosis and non-obese healthy control patients. Monocytes were evaluated by measuring expression of CD86, CD206, TLR-2 and TLR-4 as well as production of IL-6, IL-12, and by using a mycobacterial growth inhibition assay for both Mycobacterium tuberculosis and M. abscessus subsp. massiliense. Non-classical monocytes from OBDM and non-obese TB patients exhibited similar activation profiles (CD86/CD206/TLR-2 and TLR-4 expressions). Only monocytes from TB patients had a higher positivity for IL-12 and IL-6, whereas adiponectin serum levels increased similarly between TB and OBDM patients. Monocytes from active TB patients and OBDM were more permissive to Mtb growth than obese individuals, but this susceptibility was not observed for M. abscessus subsp. massiliense. From these findings, we conclude that diabetes and tuberculosis had similarities in the population of circulating non-classical monocytes, improving our understanding of the association of these diseases.

ACS Style

Danilo Pires Resende; Adeliane Castro da Costa; Lorena Pereira De Souza Rosa; Ana Paula Rodrigues; Annelisa Santos; Camila Kellen Cardoso; Jaqueline Danesio Sousa; Andre Kipnis; Erika Aparecida Silveira; Ana Paula Junqueira-Kipnis. Non-classical circulating monocytes in severe obesity and obesity with uncontrolled diabetes: A comparison with tuberculosis and healthy individuals. Tuberculosis 2018, 114, 30 -41.

AMA Style

Danilo Pires Resende, Adeliane Castro da Costa, Lorena Pereira De Souza Rosa, Ana Paula Rodrigues, Annelisa Santos, Camila Kellen Cardoso, Jaqueline Danesio Sousa, Andre Kipnis, Erika Aparecida Silveira, Ana Paula Junqueira-Kipnis. Non-classical circulating monocytes in severe obesity and obesity with uncontrolled diabetes: A comparison with tuberculosis and healthy individuals. Tuberculosis. 2018; 114 ():30-41.

Chicago/Turabian Style

Danilo Pires Resende; Adeliane Castro da Costa; Lorena Pereira De Souza Rosa; Ana Paula Rodrigues; Annelisa Santos; Camila Kellen Cardoso; Jaqueline Danesio Sousa; Andre Kipnis; Erika Aparecida Silveira; Ana Paula Junqueira-Kipnis. 2018. "Non-classical circulating monocytes in severe obesity and obesity with uncontrolled diabetes: A comparison with tuberculosis and healthy individuals." Tuberculosis 114, no. : 30-41.

Journal article
Published: 18 June 2018 in Human Vaccines & Immunotherapeutics
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Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFeO NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4IFN-γ (Th1) and CD8IFN-γ responses. Intranasal vaccination induced specific Th1, Th17 (CD4IL-17) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.

ACS Style

Lázaro Moreira Marques Neto; Nícholas Zufelato; Ailton Antônio De Sousa-Júnior; Monalisa Martins Trentini; Adeliane Castro Da Costa; Andris Bakuzis; André Kipnis; Ana Paula Junqueira-Kipnis. Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant. Human Vaccines & Immunotherapeutics 2018, 14, 1 -16.

AMA Style

Lázaro Moreira Marques Neto, Nícholas Zufelato, Ailton Antônio De Sousa-Júnior, Monalisa Martins Trentini, Adeliane Castro Da Costa, Andris Bakuzis, André Kipnis, Ana Paula Junqueira-Kipnis. Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant. Human Vaccines & Immunotherapeutics. 2018; 14 (11):1-16.

Chicago/Turabian Style

Lázaro Moreira Marques Neto; Nícholas Zufelato; Ailton Antônio De Sousa-Júnior; Monalisa Martins Trentini; Adeliane Castro Da Costa; Andris Bakuzis; André Kipnis; Ana Paula Junqueira-Kipnis. 2018. "Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant." Human Vaccines & Immunotherapeutics 14, no. 11: 1-16.

Original research article
Published: 01 June 2018 in Frontiers in Microbiology
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Mycobacterium abscessus complex has been characterized in the last decade as part of a cluster of mycobacteria that evolved from an opportunistic to true human pathogen; however, the factors responsible for pathogenicity are still undefined. It appears that the success of mycobacterial infection is intrinsically related with the capacity of the bacteria to regulate intracellular iron levels, mostly using iron storage proteins. This study evaluated two potential M. abscessus subsp. massiliense genes involved in iron storage. Unlike other opportunist or pathogenic mycobacteria studied, M. abscessus complex has two genes similar to ferritins from M. tuberculosis (Rv3841), and in M. abscessus subsp. massiliense, those genes are annotated as mycma_0076 and mycma_0077. Molecular dynamic analysis of the predicted expressed proteins showed that they have a ferroxidase center. The expressions of mycma_0076 and mycma_0077 genes were modulated by the iron levels in both in vitro cultures as well as infected macrophages. Structural studies using size-exclusion chromatography, circular dichroism spectroscopy and dynamic light scattering showed that r0076 protein has a structure similar to those observed in the ferritin family. The r0076 forms oligomers in solution most likely composed of 24 subunits. Functional studies with recombinant proteins, obtained from heterologous expression of mycma_0076 and mycma_0077 genes in Escherichia coli, showed that both proteins were capable of oxidizing Fe2+ into Fe3+, demonstrating that these proteins have a functional ferroxidase center. In conclusion, two ferritins proteins were shown, for the first time, to be involved in iron storage in M. abscessus subsp. massiliense and their expressions were modulated by the iron levels.

ACS Style

Fábio Muniz de Oliveira; Adeliane C. Da Costa; Victor O. Procopio; Wanius Garcia; Juscemácia Araujo; Roosevelt da Silva; Ana Paula Junqueira-Kipnis; Andre Kipnis. Mycobacterium abscessus subsp. massiliense mycma_0076 and mycma_0077 Genes Code for Ferritins That Are Modulated by Iron Concentration. Frontiers in Microbiology 2018, 9, 1072 .

AMA Style

Fábio Muniz de Oliveira, Adeliane C. Da Costa, Victor O. Procopio, Wanius Garcia, Juscemácia Araujo, Roosevelt da Silva, Ana Paula Junqueira-Kipnis, Andre Kipnis. Mycobacterium abscessus subsp. massiliense mycma_0076 and mycma_0077 Genes Code for Ferritins That Are Modulated by Iron Concentration. Frontiers in Microbiology. 2018; 9 ():1072.

Chicago/Turabian Style

Fábio Muniz de Oliveira; Adeliane C. Da Costa; Victor O. Procopio; Wanius Garcia; Juscemácia Araujo; Roosevelt da Silva; Ana Paula Junqueira-Kipnis; Andre Kipnis. 2018. "Mycobacterium abscessus subsp. massiliense mycma_0076 and mycma_0077 Genes Code for Ferritins That Are Modulated by Iron Concentration." Frontiers in Microbiology 9, no. : 1072.

Journal article
Published: 30 May 2018 in Toxins
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Mycobacterium massiliense is a rapid growing, multidrug-resistant, non-tuberculous mycobacteria that is responsible for a wide spectrum of skin and soft tissue infections, as well as other organs, such as the lungs. Antimicrobial peptides had been described as broad-spectrum antimicrobial, chemotactic, and immunomodulator molecules. In this study we evaluated an antimicrobial peptide derived from scorpion Tityus obscurus as an anti-mycobacterial agent in vitro and in vivo. Bioinformatics analyses demonstrated that the peptide ToAP2 have a conserved region similar to several membrane proteins, as well as mouse cathelicidin. ToAP2 inhibited the growth of four M. massiliense strains (GO01, GO06, GO08, and CRM0020) at a minimal bactericidal concentration (MBC) of 200 µM. MBC concentration used to treat infected macrophages was able to inhibit 50% of the bacterial growth of all strains. ToAP2 treatment of infected mice with bacilli reduced the bacterial load in the liver, lung, and spleen, similarly to clarithromycin levels (90%). ToAP2 alone recruited monocytes (F4/80low Gr1), neutrophils (F4/80− Gr1), and eosinophils (F4/80+ Gr1+). ToAP2, together with M. massiliense infection, was able to increase F4/80low and reduce the percentage of F4/80high macrophages when compared with infected and untreated mice. ToAP2 has in vitro anti-microbial activity that is improved in vivo due to chemotactic activity.

ACS Style

Lázaro M. Marques-Neto; Monalisa M. Trentini; Rogério C. Das Neves; Danilo P. Resende; Victor O. Procopio; Adeliane C. Da Costa; André Kipnis; Márcia R. Mortari; Elisabeth F. Schwartz; Ana Paula Junqueira-Kipnis. Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis. Toxins 2018, 10, 219 .

AMA Style

Lázaro M. Marques-Neto, Monalisa M. Trentini, Rogério C. Das Neves, Danilo P. Resende, Victor O. Procopio, Adeliane C. Da Costa, André Kipnis, Márcia R. Mortari, Elisabeth F. Schwartz, Ana Paula Junqueira-Kipnis. Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis. Toxins. 2018; 10 (6):219.

Chicago/Turabian Style

Lázaro M. Marques-Neto; Monalisa M. Trentini; Rogério C. Das Neves; Danilo P. Resende; Victor O. Procopio; Adeliane C. Da Costa; André Kipnis; Márcia R. Mortari; Elisabeth F. Schwartz; Ana Paula Junqueira-Kipnis. 2018. "Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis." Toxins 10, no. 6: 219.

Journal article
Published: 21 September 2017 in Human Vaccines & Immunotherapeutics
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Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb - associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development.

ACS Style

Bruno De Paula Oliveira Santos; Monalisa Martins Trentini; Renato Beilner Machado; Mara Rúbia Nunes Celes; Andre Kipnis; Nikolai Petrovsky; Ana Paula Junqueira-Kipnis. Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection. Human Vaccines & Immunotherapeutics 2017, 13, 2967 -2976.

AMA Style

Bruno De Paula Oliveira Santos, Monalisa Martins Trentini, Renato Beilner Machado, Mara Rúbia Nunes Celes, Andre Kipnis, Nikolai Petrovsky, Ana Paula Junqueira-Kipnis. Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection. Human Vaccines & Immunotherapeutics. 2017; 13 (12):2967-2976.

Chicago/Turabian Style

Bruno De Paula Oliveira Santos; Monalisa Martins Trentini; Renato Beilner Machado; Mara Rúbia Nunes Celes; Andre Kipnis; Nikolai Petrovsky; Ana Paula Junqueira-Kipnis. 2017. "Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection." Human Vaccines & Immunotherapeutics 13, no. 12: 2967-2976.

Research article
Published: 05 May 2017 in PLOS ONE
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Resistance to antimicrobial agents is increasing worldwide and imposes significant life-threatening risks to several different populations, especially those in intensive care units (ICUs). Bacteria can quickly develop or acquire resistance to antimicrobial drugs, and combined with their intrinsic potential to cause disease in humans, these bacteria can become deadly. Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients, and understanding the genetic basis of A. baumannii resistance to beta-lactams among patients in ICUs will result in better protocols to prevent the development of resistance as well as improved treatment regimens. In this study, we assessed 1333 patients in five ICUs, 56 of whom developed A. baumannii infections. Most of the A. baumannii isolates were resistant to beta-lactam antimicrobial drugs, specifically, 3rd- and 4th-generation cephalosporins and carbapenems, and 91.1% of the isolates were multi-drug resistant (MDR). The most frequent OXA gene present was OXA-23 (55.1%), which is significantly associated with MDR strains. Most of the A. baumannii isolates (76.8%) were capable of forming a biofilm. The antimicrobial drug classes that were effective against most of these isolates were polymyxins and tigecycline. The molecular profile of the isolates allowed detection of 12 different clusters comprising 2 to 8 isolates each. In conclusion, our data indicate a high incidence of resistance to carbapenems as well as MDR strains among the observed A. baumannii isolates, most of which exhibited a high prevalence of OXA-23 gene expression. Only a few selective drugs were effective, reinforcing the notion that bacterial resistance is an emerging problem that should be prioritized in every healthcare facility.

ACS Style

Suellen Rocha Araújo Castilho; Cássia Silva De Miranda Godoy; Adriana Oliveira Guilarde; Juliana Lamaro Cardoso; Maria Cláudia Porfirio André; Ana Paula Junqueira-Kipnis; André Kipnis. Acinetobacter baumannii strains isolated from patients in intensive care units in Goiânia, Brazil: Molecular and drug susceptibility profiles. PLOS ONE 2017, 12, e0176790 .

AMA Style

Suellen Rocha Araújo Castilho, Cássia Silva De Miranda Godoy, Adriana Oliveira Guilarde, Juliana Lamaro Cardoso, Maria Cláudia Porfirio André, Ana Paula Junqueira-Kipnis, André Kipnis. Acinetobacter baumannii strains isolated from patients in intensive care units in Goiânia, Brazil: Molecular and drug susceptibility profiles. PLOS ONE. 2017; 12 (5):e0176790.

Chicago/Turabian Style

Suellen Rocha Araújo Castilho; Cássia Silva De Miranda Godoy; Adriana Oliveira Guilarde; Juliana Lamaro Cardoso; Maria Cláudia Porfirio André; Ana Paula Junqueira-Kipnis; André Kipnis. 2017. "Acinetobacter baumannii strains isolated from patients in intensive care units in Goiânia, Brazil: Molecular and drug susceptibility profiles." PLOS ONE 12, no. 5: e0176790.

Journal article
Published: 03 May 2017 in Microbial Genomics
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An epidemic of post-surgical wound infections, caused by a non-tuberculous mycobacterium, has been on-going in Brazil. It has been unclear whether one or multiple lineages are responsible and whether their wide geographical distribution across Brazil is due to spread from a single point source or is the result of human-mediated transmission. 188 isolates, collected from nine Brazilian states, were whole genome sequenced and analysed using phylogenetic and comparative genomic approaches. The isolates from Brazil formed a single clade, which was estimated to have emerged in 2003. We observed temporal and geographic structure within the lineage that enabled us to infer the movement of sub-lineages across Brazil. The genome size of the Brazilian lineage was reduced relative to most strains in the three subspecies of Mycobacterium abscessus and contained a novel plasmid, pMAB02, in addition to the previously described pMAB01 plasmid. One lineage, which emerged just prior to the initial outbreak, is responsible for the epidemic of post-surgical wound infections in Brazil. Phylogenetic analysis indicates that multiple transmission events led to its spread. The presence of a novel plasmid and the reduced genome size suggest that the lineage has undergone adaptation to the surgical niche.

ACS Style

Izzy Everall; Christiane Lourenço Nogueira; Josephine M Bryant; Leonor Sánchez-Busó; Erica Chimara; Rafael Da Silva Duarte; Jesus Pais Ramos; Karla Valéria Batista Lima; Maria Luíza Lopes; Moises Palaci; Andre Kipnis; Fernanda Monego; R. Andres Floto; Julian Parkhill; Sylvia Cardoso Leão; Simon R Harris. Genomic epidemiology of a national outbreak of post-surgical Mycobacterium abscessus wound infections in Brazil. Microbial Genomics 2017, 3, 1 .

AMA Style

Izzy Everall, Christiane Lourenço Nogueira, Josephine M Bryant, Leonor Sánchez-Busó, Erica Chimara, Rafael Da Silva Duarte, Jesus Pais Ramos, Karla Valéria Batista Lima, Maria Luíza Lopes, Moises Palaci, Andre Kipnis, Fernanda Monego, R. Andres Floto, Julian Parkhill, Sylvia Cardoso Leão, Simon R Harris. Genomic epidemiology of a national outbreak of post-surgical Mycobacterium abscessus wound infections in Brazil. Microbial Genomics. 2017; 3 (5):1.

Chicago/Turabian Style

Izzy Everall; Christiane Lourenço Nogueira; Josephine M Bryant; Leonor Sánchez-Busó; Erica Chimara; Rafael Da Silva Duarte; Jesus Pais Ramos; Karla Valéria Batista Lima; Maria Luíza Lopes; Moises Palaci; Andre Kipnis; Fernanda Monego; R. Andres Floto; Julian Parkhill; Sylvia Cardoso Leão; Simon R Harris. 2017. "Genomic epidemiology of a national outbreak of post-surgical Mycobacterium abscessus wound infections in Brazil." Microbial Genomics 3, no. 5: 1.

Original research article
Published: 12 April 2017 in Frontiers in Microbiology
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Mycobacterium bovis Bacillus Calmette–Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses. The results demonstrate that rCMX protein expressed by BCG (rBCG-CMX) activates pulmonary macrophages; increases the expression of activation molecules, cytokines, and MHC-II. The interaction with rCMX activates the transcription factor NF-κB and induces the production of the cytokines TGF-β, TNF-α, and IL-6. The in vitro stimulation of bone marrow-derived macrophages (BMMs) from TLR-4 or TLR-2 KO mice showed that in the absence of TLR-4, IL-6 was not produced. rBCG-CMX was unable to induce CMX-specific Th1 and Th17 cells in TLR-4 and TLR-2 KO mice, suggesting that these receptors participate in their induction. We concluded that both the rBCG-CMX vaccine and the rCMX protein can activate macrophages and favor the specific immune response necessary for this vaccine.

ACS Style

Adeliane C. Da Costa; Danilo Resende; Bruno De P. O. Santos; Karina F. Zoccal; Lúcia Helena Faccioli; Andre Kipnis; Ana P. Junqueira-Kipnis. Modulation of Macrophage Responses by CMX, a Fusion Protein Composed of Ag85c, MPT51, and HspX from Mycobacterium tuberculosis. Frontiers in Microbiology 2017, 8, 623 .

AMA Style

Adeliane C. Da Costa, Danilo Resende, Bruno De P. O. Santos, Karina F. Zoccal, Lúcia Helena Faccioli, Andre Kipnis, Ana P. Junqueira-Kipnis. Modulation of Macrophage Responses by CMX, a Fusion Protein Composed of Ag85c, MPT51, and HspX from Mycobacterium tuberculosis. Frontiers in Microbiology. 2017; 8 ():623.

Chicago/Turabian Style

Adeliane C. Da Costa; Danilo Resende; Bruno De P. O. Santos; Karina F. Zoccal; Lúcia Helena Faccioli; Andre Kipnis; Ana P. Junqueira-Kipnis. 2017. "Modulation of Macrophage Responses by CMX, a Fusion Protein Composed of Ag85c, MPT51, and HspX from Mycobacterium tuberculosis." Frontiers in Microbiology 8, no. : 623.

Original research article
Published: 27 March 2017 in Frontiers in Microbiology
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Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metallo-aminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of tuberculosis, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs.

ACS Style

Andre F. Correa; Izabela Bastos; David Neves; Andre Kipnis; Ana P. Junqueira-Kipnis; Jaime M. De Santana. The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis. Frontiers in Microbiology 2017, 8, 504 .

AMA Style

Andre F. Correa, Izabela Bastos, David Neves, Andre Kipnis, Ana P. Junqueira-Kipnis, Jaime M. De Santana. The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis. Frontiers in Microbiology. 2017; 8 ():504.

Chicago/Turabian Style

Andre F. Correa; Izabela Bastos; David Neves; Andre Kipnis; Ana P. Junqueira-Kipnis; Jaime M. De Santana. 2017. "The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis." Frontiers in Microbiology 8, no. : 504.

Review article
Published: 08 March 2017 in Frontiers in Immunology
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Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen immunogenicity, aiming to induce a protective and long lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only six have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 (Th1) and Th17, and their potential functions as adjuvants for subunit vaccines.

ACS Style

Lázaro Moreira Marques Neto; André Kipnis; Ana Paula Junqueira-Kipnis. Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development. Frontiers in Immunology 2017, 8, 1 .

AMA Style

Lázaro Moreira Marques Neto, André Kipnis, Ana Paula Junqueira-Kipnis. Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development. Frontiers in Immunology. 2017; 8 ():1.

Chicago/Turabian Style

Lázaro Moreira Marques Neto; André Kipnis; Ana Paula Junqueira-Kipnis. 2017. "Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development." Frontiers in Immunology 8, no. : 1.

Original research article
Published: 22 February 2017 in Frontiers in Microbiology
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Multi-drug resistant microorganisms have been a growing concern during the last decades due to their contribution in mortality rates worldwide. Antimicrobial peptides are broad spectrum antimicrobial agents that display potent microbicidal activity against a wide range of microorganisms. Antimicrobial peptides generally have a rapid mode of action that reduces the risk of resistance developing among pathogens. In this study, an antimicrobial peptide derived from scorpion venom, NDBP-5.5, was evaluated against Mycobacterium abscessus subsp. massiliense, a rapidly growing and emerging pathogen associated with healthcare infections. The minimal bactericidal concentration of NDBP-5.5, AMP quantity necessary to stop bacteria visible growth, against M. abscessus subsp. massiliense was 200 μM, a concentration that did not induce hemolysis of human red blood cells. The therapeutic index was 3.05 indicating a drug with low toxicity and therefore good clinical potential. Treatment of infected macrophages with NDBP-5.5 or clarithromycin presented similar results, reducing the bacterial load. M. abscessus subsp. massiliense-infected animals showed a decrease in the bacterial load of up to 70% when treated with NDBP-5.5. These results revealed the effective microbicidal activity of NDBP-5.5 against mycobacterium, indicating its potential as an antimycobacterial agent.

ACS Style

Monalisa M. Trentini; Rogério C. Das Neves; Bruno De Paula Oliveira Santos; Roosevelt da Silva; Adolfo C. Barros De Souza; Márcia R. Mortari; Elisabeth F. Schwartz; Andre Kipnis; Ana P. Junqueira-Kipnis. Non-disulfide-Bridge Peptide 5.5 from the Scorpion Hadrurus gertschi Inhibits the Growth of Mycobacterium abscessus subsp. massiliense. Frontiers in Microbiology 2017, 8, 273 .

AMA Style

Monalisa M. Trentini, Rogério C. Das Neves, Bruno De Paula Oliveira Santos, Roosevelt da Silva, Adolfo C. Barros De Souza, Márcia R. Mortari, Elisabeth F. Schwartz, Andre Kipnis, Ana P. Junqueira-Kipnis. Non-disulfide-Bridge Peptide 5.5 from the Scorpion Hadrurus gertschi Inhibits the Growth of Mycobacterium abscessus subsp. massiliense. Frontiers in Microbiology. 2017; 8 ():273.

Chicago/Turabian Style

Monalisa M. Trentini; Rogério C. Das Neves; Bruno De Paula Oliveira Santos; Roosevelt da Silva; Adolfo C. Barros De Souza; Márcia R. Mortari; Elisabeth F. Schwartz; Andre Kipnis; Ana P. Junqueira-Kipnis. 2017. "Non-disulfide-Bridge Peptide 5.5 from the Scorpion Hadrurus gertschi Inhibits the Growth of Mycobacterium abscessus subsp. massiliense." Frontiers in Microbiology 8, no. : 273.

Journal article
Published: 01 February 2017 in International Journal of Antimicrobial Agents
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Mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. Among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. Thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp Pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (Staphylococcus aureus and Mycobacterium abscessus subsp. massiliense), fungi (Candida albicans and Cryptococcus neoformans) and in vivo S. aureus infection. The membrane pore-forming ability was also assessed. The mastoparan reduced in vitro and ex vivo mycobacterial growth by 80% at 12.5 µM in infected peritoneal macrophages but did not affect the shape of bacterial cells at the dose tested (6.25 µM). The peptide also showed potent action against S. aureus in vitro (EC and EC values of 1.83 µM and 2.90 µM, respectively) and reduced the in vivo bacterial load after 6 days of topical treatment (5 mg/kg). Antifungal activity was significant, with EC and EC values of 12.9 µM and 15.3 µM, respectively, for C. albicans, and 11 µM and 22.70 µM, respectively, for C. neoformans. Peptides are currently attracting interest for their potential in the design of antimicrobial drugs, particularly due to the difficulty of micro-organisms in developing resistance to them. In this respect, Polybia-MPII proved to be highly effective, with a lower haemolysis rate compared with peptides of the same family.

ACS Style

Juliana C. Silva; Lázaro M. Neto; Rogério C. Neves; Jaqueline C. Gonçalves; Monalisa M. Trentini; Ricardo Mucury-Filho; Karina S. Smidt; Isabel C. Fensterseifer; Osmar N. Silva; Lilian D. Lima; Patricia B. Clissa; Nathália Vilela; Fernanda Guilhelmelli; Luciano P. Silva; Marisa Rangel; Andre Kipnis; Ildinete Silva Pereira; Octavio Franco; Ana P. Junqueira-Kipnis; Anamélia Lorenzetti Bocca; Márcia R. Mortari. Evaluation of the antimicrobial activity of the mastoparan Polybia-MPII isolated from venom of the social wasp Pseudopolybia vespiceps testacea (Vespidae, Hymenoptera). International Journal of Antimicrobial Agents 2017, 49, 167 -175.

AMA Style

Juliana C. Silva, Lázaro M. Neto, Rogério C. Neves, Jaqueline C. Gonçalves, Monalisa M. Trentini, Ricardo Mucury-Filho, Karina S. Smidt, Isabel C. Fensterseifer, Osmar N. Silva, Lilian D. Lima, Patricia B. Clissa, Nathália Vilela, Fernanda Guilhelmelli, Luciano P. Silva, Marisa Rangel, Andre Kipnis, Ildinete Silva Pereira, Octavio Franco, Ana P. Junqueira-Kipnis, Anamélia Lorenzetti Bocca, Márcia R. Mortari. Evaluation of the antimicrobial activity of the mastoparan Polybia-MPII isolated from venom of the social wasp Pseudopolybia vespiceps testacea (Vespidae, Hymenoptera). International Journal of Antimicrobial Agents. 2017; 49 (2):167-175.

Chicago/Turabian Style

Juliana C. Silva; Lázaro M. Neto; Rogério C. Neves; Jaqueline C. Gonçalves; Monalisa M. Trentini; Ricardo Mucury-Filho; Karina S. Smidt; Isabel C. Fensterseifer; Osmar N. Silva; Lilian D. Lima; Patricia B. Clissa; Nathália Vilela; Fernanda Guilhelmelli; Luciano P. Silva; Marisa Rangel; Andre Kipnis; Ildinete Silva Pereira; Octavio Franco; Ana P. Junqueira-Kipnis; Anamélia Lorenzetti Bocca; Márcia R. Mortari. 2017. "Evaluation of the antimicrobial activity of the mastoparan Polybia-MPII isolated from venom of the social wasp Pseudopolybia vespiceps testacea (Vespidae, Hymenoptera)." International Journal of Antimicrobial Agents 49, no. 2: 167-175.