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Dr. Marc Maresca
Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France

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0 Mycotoxins
0 antibacterial agents
0 food contaminants
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Mycotoxins
antimicrobial peptides (AMPs)
antibacterial agents
Antimicrobial agents

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Journal article
Published: 22 July 2021 in Molecules
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Psophocarpus tetragonolobus has long been used in traditional medicine and cuisine. In this study, Psophocarpus tetragonolobus extracts were isolated by maceration and ultrasound-assisted extraction and were evaluated for their antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The obtained results show that both extracts (maceration and ultrasound) were rich in bioactive molecules and exerted substantial antioxidant and anti-inflammatory effects. The P. tetragonolobus extracts’ treatment in LPS-stimulated RAW264.7 macrophages resulted in a significant downregulation of the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA. In addition, the P. tetragonolobus extracts’ treatment attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression. Our observations indicate that there is no significant difference between the two studied extracts of P. tetragonolobus in terms of biological properties (specifically, antioxidant and anti-inflammatory effects. Regardless of the extraction method, P. tetragonolobus could be used for treating diseases related to oxidative stress and inflammatory reactions.

ACS Style

Hussein Bassal; Akram Hijazi; Hussein Farhan; Christine Trabolsi; Bouchra Ahmad; Alia Khalil; Marc Maresca; Fawaz El Omar. Study of the Antioxidant and Anti-Inflammatory Properties of the Biological Extracts of Psophocarpus tetragonolobus Using Two Extraction Methods. Molecules 2021, 26, 4435 .

AMA Style

Hussein Bassal, Akram Hijazi, Hussein Farhan, Christine Trabolsi, Bouchra Ahmad, Alia Khalil, Marc Maresca, Fawaz El Omar. Study of the Antioxidant and Anti-Inflammatory Properties of the Biological Extracts of Psophocarpus tetragonolobus Using Two Extraction Methods. Molecules. 2021; 26 (15):4435.

Chicago/Turabian Style

Hussein Bassal; Akram Hijazi; Hussein Farhan; Christine Trabolsi; Bouchra Ahmad; Alia Khalil; Marc Maresca; Fawaz El Omar. 2021. "Study of the Antioxidant and Anti-Inflammatory Properties of the Biological Extracts of Psophocarpus tetragonolobus Using Two Extraction Methods." Molecules 26, no. 15: 4435.

Review
Published: 03 April 2021 in Biomolecules
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Cancer is a challenging problem for the global health community, and its increasing burden necessitates seeking novel and alternative therapies. Most cancers share six basic characteristics known as “cancer hallmarks”, including uncontrolled proliferation, refractoriness to proliferation blockers, escaping apoptosis, unlimited proliferation, enhanced angiogenesis, and metastatic spread. Apoptosis, as one of the best-known programmed cell death processes, is generally promoted through two signaling pathways, including the intrinsic and extrinsic cascades. These pathways comprise several components that their alterations can render an apoptosis-resistance phenotype to the cell. Therefore, targeting more than one molecule in apoptotic pathways can be a novel and efficient approach for both identifying new anticancer therapeutics and preventing resistance to therapy. The main purpose of this review is to summarize data showing that various plant extracts and plant-derived molecules can activate both intrinsic and extrinsic apoptosis pathways in human cancer cells, making them attractive candidates in cancer treatment.

ACS Style

Sadegh Rajabi; Marc Maresca; Alexei Yumashev; Rasool Choopani; Homa Hajimehdipoor. The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules 2021, 11, 534 .

AMA Style

Sadegh Rajabi, Marc Maresca, Alexei Yumashev, Rasool Choopani, Homa Hajimehdipoor. The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules. 2021; 11 (4):534.

Chicago/Turabian Style

Sadegh Rajabi; Marc Maresca; Alexei Yumashev; Rasool Choopani; Homa Hajimehdipoor. 2021. "The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy." Biomolecules 11, no. 4: 534.

Journal article
Published: 23 March 2021 in International Journal of Molecular Sciences
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The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

ACS Style

Clarisse Roblin; Steve Chiumento; Cédric Jacqueline; Eric Pinloche; Cendrine Nicoletti; Hamza Olleik; Elise Courvoisier-Dezord; Agnès Amouric; Christian Basset; Louis Dru; Marie Ollivier; Aurélie Bogey-Lambert; Nicolas Vidal; Mohamed Atta; Marc Maresca; Estelle Devillard; Victor Duarte; Josette Perrier; Mickael Lafond. The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health. International Journal of Molecular Sciences 2021, 22, 3253 .

AMA Style

Clarisse Roblin, Steve Chiumento, Cédric Jacqueline, Eric Pinloche, Cendrine Nicoletti, Hamza Olleik, Elise Courvoisier-Dezord, Agnès Amouric, Christian Basset, Louis Dru, Marie Ollivier, Aurélie Bogey-Lambert, Nicolas Vidal, Mohamed Atta, Marc Maresca, Estelle Devillard, Victor Duarte, Josette Perrier, Mickael Lafond. The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health. International Journal of Molecular Sciences. 2021; 22 (6):3253.

Chicago/Turabian Style

Clarisse Roblin; Steve Chiumento; Cédric Jacqueline; Eric Pinloche; Cendrine Nicoletti; Hamza Olleik; Elise Courvoisier-Dezord; Agnès Amouric; Christian Basset; Louis Dru; Marie Ollivier; Aurélie Bogey-Lambert; Nicolas Vidal; Mohamed Atta; Marc Maresca; Estelle Devillard; Victor Duarte; Josette Perrier; Mickael Lafond. 2021. "The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health." International Journal of Molecular Sciences 22, no. 6: 3253.

Journal article
Published: 05 February 2021 in Molecules
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Chronic cerebral ischemia with a notable long-term cessation of blood supply to the brain tissues leads to sensorimotor defects and short- and long-term memory problems. Neuroprotective agents are used in an attempt to save ischemic neurons from necrosis and apoptosis, such as the antioxidant agent Eucalyptus. Numerous studies have demonstrated the involvement of the renin-angiotensin system in the initiation and progression of cardiovascular and neurodegenerative diseases. Candesartan is a drug that acts as an angiotensin II receptor 1 blocker. We established a rat model exhibiting sensorimotor and cognitive impairments due to chronic cerebral ischemia induced by the ligation of the right common carotid artery. Wistar male rats were randomly divided into five groups: Sham group, Untreated Ligated group, Ischemic group treated with Eucalyptus (500 mg/kg), Ischemic group treated with Candesartan (0.5 mg/kg), and Ischemic group treated with a combination of Eucalyptus and Candesartan. To evaluate the sensorimotor disorders, we performed the beam balance test, the beam walking test, and the modified sticky test. Moreover, the object recognition test and the Morris water maze test were performed to assess the memory disorders of the rats. The infarct rat brain regions were subsequently stained using the triphenyltetrazolium chloride staining technique. The rats in the Sham group had normal sensorimotor and cognitive functions without the appearance of microscopic ischemic brain lesions. In parallel, the untreated Ischemic group showed severe impaired neurological functions with the presence of considerable brain infarctions. The treatment of the Ischemic group with a combination of both Eucalyptus and Candesartan was more efficient in improving the sensorimotor and cognitive deficits (p < 0.001) than the treatment with Eucalyptus or Candesartan alone (p < 0.05), by the comparison to the non-treated Ischemic group. Our study shows that the combination of Eucalyptus and Candesartan could decrease ischemic brain injury and improve neurological outcomes.

ACS Style

Christine Trabolsi; Wafaa Takash Chamoun; Akram Hijazi; Cendrine Nicoletti; Marc Maresca; Mohamad Nasser. Study of Neuroprotection by a Combination of the Biological Antioxidant (Eucalyptus Extract) and the Antihypertensive Drug Candesartan against Chronic Cerebral Ischemia in Rats. Molecules 2021, 26, 839 .

AMA Style

Christine Trabolsi, Wafaa Takash Chamoun, Akram Hijazi, Cendrine Nicoletti, Marc Maresca, Mohamad Nasser. Study of Neuroprotection by a Combination of the Biological Antioxidant (Eucalyptus Extract) and the Antihypertensive Drug Candesartan against Chronic Cerebral Ischemia in Rats. Molecules. 2021; 26 (4):839.

Chicago/Turabian Style

Christine Trabolsi; Wafaa Takash Chamoun; Akram Hijazi; Cendrine Nicoletti; Marc Maresca; Mohamad Nasser. 2021. "Study of Neuroprotection by a Combination of the Biological Antioxidant (Eucalyptus Extract) and the Antihypertensive Drug Candesartan against Chronic Cerebral Ischemia in Rats." Molecules 26, no. 4: 839.

Journal article
Published: 07 January 2021 in Antioxidants
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The present study aims to investigate the properties of biopolymers extracted from a Lebanese onion non edible plant. The extraction was performed under mild conditions by varying the percentage of ultra-sound (US) treatment duration to a total extraction time of 30 min (0, 50, 100% US). The extracts were characterized using FTIR, SEC, GC-MS, TGA, and DSC analyses. The composition of the extracts was determined from the total carbohydrate content and protein content measurements. The thermal analyses indicate that all samples have high thermal stability. The antioxidant activities of the extracts were investigated, using β-carotene bleaching, scavenging activity of ABTS, metal chelating ability, and total antioxidant activity tests. The results indicate that the 50% US treatment leads to the best antioxidant activity. Biocompatibility of the extracts was evaluated using hemolysis and cytotoxicity assays. The results showed that 0 and 50% US samples are not toxic to human cells, in contrary to 100% US.

ACS Style

Mohammad Kazem Medlej; Cherri Batoul; Hamza Olleik; Suming Li; Akram Hijazi; Ghassan Nasser; Marc Maresca; Céline Pochat-Bohatier. Antioxidant Activity and Biocompatibility of Fructo-Polysaccharides Extracted from a Wild Species of Ornithogalum from Lebanon. Antioxidants 2021, 10, 68 .

AMA Style

Mohammad Kazem Medlej, Cherri Batoul, Hamza Olleik, Suming Li, Akram Hijazi, Ghassan Nasser, Marc Maresca, Céline Pochat-Bohatier. Antioxidant Activity and Biocompatibility of Fructo-Polysaccharides Extracted from a Wild Species of Ornithogalum from Lebanon. Antioxidants. 2021; 10 (1):68.

Chicago/Turabian Style

Mohammad Kazem Medlej; Cherri Batoul; Hamza Olleik; Suming Li; Akram Hijazi; Ghassan Nasser; Marc Maresca; Céline Pochat-Bohatier. 2021. "Antioxidant Activity and Biocompatibility of Fructo-Polysaccharides Extracted from a Wild Species of Ornithogalum from Lebanon." Antioxidants 10, no. 1: 68.

Journal article
Published: 16 December 2020 in Biomolecules
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Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur4-2-Nal3-Ala2-Phe1-CONH2) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC50 = 0.15 ± 0.05 µg/mL or 0.28 +/− 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, 1H- NMR, 13C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.

ACS Style

Hunain Ali; Almas Jabeen; Rukesh Maharjan; Muhammad Nadeem-Ul-Haque; Husena Aamra; Salma Nazir; Serab Khan; Hamza Olleik; Marc Maresca; Farzana Shaheen. Furan-Conjugated Tripeptides as Potent Antitumor Drugs. Biomolecules 2020, 10, 1684 .

AMA Style

Hunain Ali, Almas Jabeen, Rukesh Maharjan, Muhammad Nadeem-Ul-Haque, Husena Aamra, Salma Nazir, Serab Khan, Hamza Olleik, Marc Maresca, Farzana Shaheen. Furan-Conjugated Tripeptides as Potent Antitumor Drugs. Biomolecules. 2020; 10 (12):1684.

Chicago/Turabian Style

Hunain Ali; Almas Jabeen; Rukesh Maharjan; Muhammad Nadeem-Ul-Haque; Husena Aamra; Salma Nazir; Serab Khan; Hamza Olleik; Marc Maresca; Farzana Shaheen. 2020. "Furan-Conjugated Tripeptides as Potent Antitumor Drugs." Biomolecules 10, no. 12: 1684.

Full paper
Published: 07 December 2020 in Chemistry – A European Journal
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Tyrosinase enzymes (Tys) are involved in the key steps of melanin (protective pigments) biosynthesis and molecules targeting the binuclear copper active site on tyrosinases represent a relevant strategy to regulate enzyme activities. In this work, we studied the possible synergic effect generated by combination of known inhibitors. For this, derivatives containing kojic acid (KA) and 2‐Hydroxypyridine‐ N ‐oxide (HOPNO) combined with a thiosemicarbazone (TSC) moiety were synthetized. Their inhibition activities were evaluated on purified tyrosinases from different sources (mushroom, bacterial and human) as well as on melanin production by lysats from human melanoma MNT‐1 cell line. Results showed significant enhancement of the inhibitory effects compared to the parent compounds, in particular for HOPNO‐TSC. In order to elucidate the interaction mode with the dicopper(II) active site, we investigated the binding studies towards a tyrosinase bio‐inspired model of the dicopper(II) center. The structure of the isolated adduct between one ditopic inhibitor (KA‐TSC) and the model complex reveals that the binding to a dicopper center can occur with both chelating sites. Computational studies on model complexes and docking studies on enzymes led to the identification of KA and HOPNO moieties as interacting groups with the dicopper active site.

ACS Style

Elina Buitrago; Clarisse Faure; Lylia Challali; Elisabetta Bergantino; Ahcène Boumendjel; Luigi Bubacco; Marcello Carotti; Renaud Hardré; Marc Maresca; Christian Philouze; Hélène Jamet; Marius Réglier; Catherine Belle. Ditopic Chelators of Dicopper Centers for Enhanced Tyrosinases Inhibition. Chemistry – A European Journal 2020, 27, 4384 -4393.

AMA Style

Elina Buitrago, Clarisse Faure, Lylia Challali, Elisabetta Bergantino, Ahcène Boumendjel, Luigi Bubacco, Marcello Carotti, Renaud Hardré, Marc Maresca, Christian Philouze, Hélène Jamet, Marius Réglier, Catherine Belle. Ditopic Chelators of Dicopper Centers for Enhanced Tyrosinases Inhibition. Chemistry – A European Journal. 2020; 27 (13):4384-4393.

Chicago/Turabian Style

Elina Buitrago; Clarisse Faure; Lylia Challali; Elisabetta Bergantino; Ahcène Boumendjel; Luigi Bubacco; Marcello Carotti; Renaud Hardré; Marc Maresca; Christian Philouze; Hélène Jamet; Marius Réglier; Catherine Belle. 2020. "Ditopic Chelators of Dicopper Centers for Enhanced Tyrosinases Inhibition." Chemistry – A European Journal 27, no. 13: 4384-4393.

Journal article
Published: 27 July 2020 in Proceedings of the National Academy of Sciences
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The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced byRuminococcus gnavusE1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

ACS Style

Clarisse Roblin; Steve Chiumento; Olivier Bornet; Matthieu Nouailler; Christina S. Müller; Katy Jeannot; Christian Basset; Sylvie Kieffer-Jaquinod; Yohann Couté; Stéphane Torelli; Laurent Le Pape; Volker Schünemann; Hamza Olleik; Bruno De La Villeon; Philippe Sockeel; Eric Di Pasquale; Cendrine Nicoletti; Nicolas Vidal; Leonora Poljak; Olga Iranzo; Thierry Giardina; Michel Fons; Estelle Devillard; Patrice Polard; Marc Maresca; Josette Perrier; Mohamed Atta; Françoise Guerlesquin; Mickael Lafond; Victor Duarte. The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties. Proceedings of the National Academy of Sciences 2020, 117, 19168 -19177.

AMA Style

Clarisse Roblin, Steve Chiumento, Olivier Bornet, Matthieu Nouailler, Christina S. Müller, Katy Jeannot, Christian Basset, Sylvie Kieffer-Jaquinod, Yohann Couté, Stéphane Torelli, Laurent Le Pape, Volker Schünemann, Hamza Olleik, Bruno De La Villeon, Philippe Sockeel, Eric Di Pasquale, Cendrine Nicoletti, Nicolas Vidal, Leonora Poljak, Olga Iranzo, Thierry Giardina, Michel Fons, Estelle Devillard, Patrice Polard, Marc Maresca, Josette Perrier, Mohamed Atta, Françoise Guerlesquin, Mickael Lafond, Victor Duarte. The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties. Proceedings of the National Academy of Sciences. 2020; 117 (32):19168-19177.

Chicago/Turabian Style

Clarisse Roblin; Steve Chiumento; Olivier Bornet; Matthieu Nouailler; Christina S. Müller; Katy Jeannot; Christian Basset; Sylvie Kieffer-Jaquinod; Yohann Couté; Stéphane Torelli; Laurent Le Pape; Volker Schünemann; Hamza Olleik; Bruno De La Villeon; Philippe Sockeel; Eric Di Pasquale; Cendrine Nicoletti; Nicolas Vidal; Leonora Poljak; Olga Iranzo; Thierry Giardina; Michel Fons; Estelle Devillard; Patrice Polard; Marc Maresca; Josette Perrier; Mohamed Atta; Françoise Guerlesquin; Mickael Lafond; Victor Duarte. 2020. "The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties." Proceedings of the National Academy of Sciences 117, no. 32: 19168-19177.

Journal article
Published: 06 July 2020 in Antibiotics
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The biological activities of berberine, a natural plant molecule, are known to be affected by structural modifications, mostly at position 9 and/or 13. A series of new 13-substituted berberine derivatives were synthesized and evaluated in term of antimicrobial activity using various microorganisms associated to human diseases. Contrarily to the original molecule berberine, several derivatives were found strongly active in microbial sensitivity tests against Mycobacterium, Candida albicans and Gram-positive bacteria, including naïve or resistant Bacillus cereus, Staphylococcus aureus and Streptococcus pyogenes with minimal inhibitory concentration (MIC) of 3.12 to 6.25 µM. Among the various Gram-negative strains tested, berberine’s derivatives were only found active on Helicobacter pylori and Vibrio alginolyticus (MIC values of 1.5–3.12 µM). Cytotoxicity assays performed on human cells showed that the antimicrobial berberine derivatives caused low toxicity resulting in good therapeutic index values. In addition, a mechanistic approach demonstrated that, contrarily to already known berberine derivatives causing either membrane permeabilization, DNA fragmentation or interacting with FtsZ protein, active derivatives described in this study act through inhibition of the synthesis of peptidoglycan or RNA. Overall, this study shows that these new berberine derivatives can be considered as potent and safe anti-bacterial agents active on human pathogenic microorganisms, including ones resistant to conventional antibiotics.

ACS Style

Hamza Olleik; Taher Yacoub; Laurent Hoffer; Senankpon Martial Gnansounou; Kehna Benhaiem-Henry; Cendrine Nicoletti; Malika Mekhalfi; Valerie Pique; Josette Perrier; Akram Hijazi; Elias Baydoun; Josette Raymond; Philippe Piccerelle; Marc Maresca; Maxime Robin. Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives. Antibiotics 2020, 9, 381 .

AMA Style

Hamza Olleik, Taher Yacoub, Laurent Hoffer, Senankpon Martial Gnansounou, Kehna Benhaiem-Henry, Cendrine Nicoletti, Malika Mekhalfi, Valerie Pique, Josette Perrier, Akram Hijazi, Elias Baydoun, Josette Raymond, Philippe Piccerelle, Marc Maresca, Maxime Robin. Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives. Antibiotics. 2020; 9 (7):381.

Chicago/Turabian Style

Hamza Olleik; Taher Yacoub; Laurent Hoffer; Senankpon Martial Gnansounou; Kehna Benhaiem-Henry; Cendrine Nicoletti; Malika Mekhalfi; Valerie Pique; Josette Perrier; Akram Hijazi; Elias Baydoun; Josette Raymond; Philippe Piccerelle; Marc Maresca; Maxime Robin. 2020. "Synthesis and Evaluation of the Antibacterial Activities of 13-Substituted Berberine Derivatives." Antibiotics 9, no. 7: 381.

Journal article
Published: 24 December 2019 in Biomolecules
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Seven naphtho-gamma-pyrones (NγPs), including asperpyrone E, aurasperone A, dianhydroaurasperone C, fonsecin, fonsecinone A, fonsecin B, and ustilaginoidin A, were isolated from Aspergillus tubingensis G131, a non-toxigenic strain. The radical scavenging activity of these NγPs was evaluated using ABTS assay. The Trolox equivalent antioxidant capacity on the seven isolated NγPs ranged from 2.4 to 14.6 μmol L−1. The toxicity and ability of the NγPs to prevent H2O2-mediated cell death were evaluated using normal/not cancerous cells (CHO cells). This cell-based assay showed that NγPs: (1) Are not toxic or weakly toxic towards cells and (2) are able to protect cells from oxidant injuries with an IC50 on H2O2-mediated cell death ranging from 2.25 to 1800 μmol mL−1. Our data show that A. tubingensis G131 strain is able to produce various NγPs possessing strong antioxidant activities and low toxicities, making this strain a good candidate for antioxidant applications in food and cosmetic industries.

ACS Style

Quentin Carboué; Marc Maresca; Gaëtan Herbette; Sevastianos Roussos; Rayhane Hamrouni; Isabelle Bombarda. Naphtho-Gamma-Pyrones Produced by Aspergillus tubingensis G131: New Source of Natural Nontoxic Antioxidants. Biomolecules 2019, 10, 29 .

AMA Style

Quentin Carboué, Marc Maresca, Gaëtan Herbette, Sevastianos Roussos, Rayhane Hamrouni, Isabelle Bombarda. Naphtho-Gamma-Pyrones Produced by Aspergillus tubingensis G131: New Source of Natural Nontoxic Antioxidants. Biomolecules. 2019; 10 (1):29.

Chicago/Turabian Style

Quentin Carboué; Marc Maresca; Gaëtan Herbette; Sevastianos Roussos; Rayhane Hamrouni; Isabelle Bombarda. 2019. "Naphtho-Gamma-Pyrones Produced by Aspergillus tubingensis G131: New Source of Natural Nontoxic Antioxidants." Biomolecules 10, no. 1: 29.

Journal article
Published: 11 October 2019 in Biomolecules
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Helicobacterpylori is one of the most prevalent pathogens colonizing 50% of the world’s population and causing gastritis and gastric cancer. Even with triple and quadruple antibiotic therapies, H. pylori shows increased prevalence of resistance to conventional antibiotics and treatment failure. Due to their pore-forming activity, antimicrobial peptides (AMP) are considered as a good alternative to conventional antibiotics, particularly in the case of resistant bacteria. In this study, temporin-SHa (a frog AMP) and its analogs obtained by Gly to Ala substitutions were tested against H. pylori. Results showed differences in the antibacterial activity and toxicity of the peptides in relation to the number and position of D-Ala substitution. Temporin-SHa and its analog NST1 were identified as the best molecules, both peptides being active on clinical resistant strains, killing 90–100% of bacteria in less than 1 h and showing low to no toxicity against human gastric cells and tissue. Importantly, the presence of gastric mucins did not prevent the antibacterial effect of temporin-SHa and NST1, NST1 being in addition resistant to pepsin. Taken together, our results demonstrated that temporin-SHa and its analog NST1 could be considered as potential candidates to treat H. pylori, particularly in the case of resistant strains.

ACS Style

Hamza Olleik; Elias Baydoun; Josette Perrier; Akram Hijazi; Josette Raymond; Marine Manzoni; Lucas Dupuis; Ghislain Pauleau; Yvain Goudard; Bruno De La Villéon; Géraldine Goin; Philippe Sockeel; Muhammad Iqbal Choudhary; Eric Di Pasquale; Muhammad Nadeem-Ul-Haque; Hunain Ali; Arif Iftikhar Khan; Farzana Shaheen; Marc Maresca. Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori. Biomolecules 2019, 9, 598 .

AMA Style

Hamza Olleik, Elias Baydoun, Josette Perrier, Akram Hijazi, Josette Raymond, Marine Manzoni, Lucas Dupuis, Ghislain Pauleau, Yvain Goudard, Bruno De La Villéon, Géraldine Goin, Philippe Sockeel, Muhammad Iqbal Choudhary, Eric Di Pasquale, Muhammad Nadeem-Ul-Haque, Hunain Ali, Arif Iftikhar Khan, Farzana Shaheen, Marc Maresca. Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori. Biomolecules. 2019; 9 (10):598.

Chicago/Turabian Style

Hamza Olleik; Elias Baydoun; Josette Perrier; Akram Hijazi; Josette Raymond; Marine Manzoni; Lucas Dupuis; Ghislain Pauleau; Yvain Goudard; Bruno De La Villéon; Géraldine Goin; Philippe Sockeel; Muhammad Iqbal Choudhary; Eric Di Pasquale; Muhammad Nadeem-Ul-Haque; Hunain Ali; Arif Iftikhar Khan; Farzana Shaheen; Marc Maresca. 2019. "Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori." Biomolecules 9, no. 10: 598.

Research article
Published: 25 September 2019 in Science Advances
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A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated withRuminococcus gnavusE1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenicClostridiaand multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strainR. gnavusE1 as a relevant probiotic for gut health enhancement.

ACS Style

Steve Chiumento; Clarisse Roblin; Sylvie Kieffer-Jaquinod; Sybille Tachon; Chloé Leprètre; Christian Basset; Dwi Aditiyarini; Hamza Olleik; Cendrine Nicoletti; Olivier Bornet; Olga Iranzo; Marc Maresca; Renaud Hardré; Michel Fons; Thierry Giardina; Estelle Devillard; Françoise Guerlesquin; Yohann Couté; Mohamed Atta; Josette Perrier; Mickael Lafond; Victor Duarte. Ruminococcin C, a promising antibiotic produced by a human gut symbiont. Science Advances 2019, 5, eaaw9969 .

AMA Style

Steve Chiumento, Clarisse Roblin, Sylvie Kieffer-Jaquinod, Sybille Tachon, Chloé Leprètre, Christian Basset, Dwi Aditiyarini, Hamza Olleik, Cendrine Nicoletti, Olivier Bornet, Olga Iranzo, Marc Maresca, Renaud Hardré, Michel Fons, Thierry Giardina, Estelle Devillard, Françoise Guerlesquin, Yohann Couté, Mohamed Atta, Josette Perrier, Mickael Lafond, Victor Duarte. Ruminococcin C, a promising antibiotic produced by a human gut symbiont. Science Advances. 2019; 5 (9):eaaw9969.

Chicago/Turabian Style

Steve Chiumento; Clarisse Roblin; Sylvie Kieffer-Jaquinod; Sybille Tachon; Chloé Leprètre; Christian Basset; Dwi Aditiyarini; Hamza Olleik; Cendrine Nicoletti; Olivier Bornet; Olga Iranzo; Marc Maresca; Renaud Hardré; Michel Fons; Thierry Giardina; Estelle Devillard; Françoise Guerlesquin; Yohann Couté; Mohamed Atta; Josette Perrier; Mickael Lafond; Victor Duarte. 2019. "Ruminococcin C, a promising antibiotic produced by a human gut symbiont." Science Advances 5, no. 9: eaaw9969.

Journal article
Published: 03 September 2019 in Toxins
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Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these peptides are not novel, comparative studies of their antimicrobial activity, toxicity, and mechanism of action are still to be identified. In this study, the fungal cyclohexadepsipeptides enniatin (ENN) and beauvericin (BEA) were assessed to determine their antimicrobial activity and cytotoxicity against human cells. Results showed that these peptides were active against Gram-positive bacteria, Mycobacterium, and fungi, but not against Gram-negative bacteria. ENN and BEA had a limited hemolytic effect, yet were found to be toxic at low doses to nucleated human cells. Both peptides also interacted with bacterial lipids, causing low to no membrane permeabilization, but induced membrane depolarization and inhibition of macromolecules synthesis. The structure-activity analysis showed that the chemical nature of the side chains present on ENN and BEA (either iso-propyl, sec-butyl, or phenylmethyl) impacts their interaction with lipids, antimicrobial action, and toxicity.

ACS Style

Hamza Olleik; Cendrine Nicoletti; Mickael Lafond; Elise Courvoisier-Dezord; Peiwen Xue; Akram Hijazi; Elias Baydoun; Josette Perrier; Marc Maresca. Comparative Structure-Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin. Toxins 2019, 11, 514 .

AMA Style

Hamza Olleik, Cendrine Nicoletti, Mickael Lafond, Elise Courvoisier-Dezord, Peiwen Xue, Akram Hijazi, Elias Baydoun, Josette Perrier, Marc Maresca. Comparative Structure-Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin. Toxins. 2019; 11 (9):514.

Chicago/Turabian Style

Hamza Olleik; Cendrine Nicoletti; Mickael Lafond; Elise Courvoisier-Dezord; Peiwen Xue; Akram Hijazi; Elias Baydoun; Josette Perrier; Marc Maresca. 2019. "Comparative Structure-Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin." Toxins 11, no. 9: 514.

Review
Published: 29 August 2019 in Marine Drugs
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Antimicrobial peptides (AMPs) are natural antibiotics produced by all living organisms. In metazoans, they act as host defense factors by eliminating microbial pathogens. But they also help to select the colonizing bacterial symbionts while coping with specific environmental challenges. Although many AMPs share common structural characteristics, for example having an overall size between 10–100 amino acids, a net positive charge, a γ-core motif, or a high content of cysteines, they greatly differ in coding sequences as a consequence of multiple parallel evolution in the face of pathogens. The majority of AMPs is specific of certain taxa or even typifying species. This is especially the case of annelids (ringed worms). Even in regions with extreme environmental conditions (polar, hydrothermal, abyssal, polluted, etc.), worms have colonized all habitats on Earth and dominated in biomass most of them while co-occurring with a large number and variety of bacteria. This review surveys the different structures and functions of AMPs that have been so far encountered in annelids and nematodes. It highlights the wide diversity of AMP primary structures and their originality that presumably mimics the highly diverse life styles and ecology of worms. From the unique system that represents marine annelids, we have studied the effect of abiotic pressures on the selection of AMPs and demonstrated the promising sources of antibiotics that they could constitute.

ACS Style

Renato Bruno; Marc Maresca; Stéphane Canaan; Jean-François Cavalier; Kamel Mabrouk; Céline Boidin-Wichlacz; Hamza Olleik; Daniela Zeppilli; Priscille Brodin; François Massol; Didier Jollivet; Sascha Jung; Aurélie Tasiemski; Boidin- Wichlacz; Jung. Worms’ Antimicrobial Peptides. Marine Drugs 2019, 17, 512 .

AMA Style

Renato Bruno, Marc Maresca, Stéphane Canaan, Jean-François Cavalier, Kamel Mabrouk, Céline Boidin-Wichlacz, Hamza Olleik, Daniela Zeppilli, Priscille Brodin, François Massol, Didier Jollivet, Sascha Jung, Aurélie Tasiemski, Boidin- Wichlacz, Jung. Worms’ Antimicrobial Peptides. Marine Drugs. 2019; 17 (9):512.

Chicago/Turabian Style

Renato Bruno; Marc Maresca; Stéphane Canaan; Jean-François Cavalier; Kamel Mabrouk; Céline Boidin-Wichlacz; Hamza Olleik; Daniela Zeppilli; Priscille Brodin; François Massol; Didier Jollivet; Sascha Jung; Aurélie Tasiemski; Boidin- Wichlacz; Jung. 2019. "Worms’ Antimicrobial Peptides." Marine Drugs 17, no. 9: 512.

Original paper
Published: 14 June 2019 in Molecular Biotechnology
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1-Aminocyclopropane carboxylic acid oxidase (ACCO) catalyzes the last step of ethylene biosynthesis in plants. Although some sets of structures have been described, there are remaining questions on the active conformation of ACCO and in particular, on the conformation and potential flexibility of the C-terminal part of the enzyme. Several techniques based on the introduction of a probe through chemical modification of amino acid residues have been developed for determining the conformation and dynamics of proteins. Cysteine residues are recognized as convenient targets for selective chemical modification of proteins, thanks to their relatively low abundance in protein sequences and to their well-mastered chemical reactivity. ACCOs have generally 3 or 4 cysteine residues in their sequences. By a combination of approaches including directed mutagenesis, activity screening on cell extracts, biophysical and biochemical characterization of purified enzymes, we evaluated the effect of native cysteine replacement and that of insertion of cysteines on the C-terminal part in tomato ACCO. Moreover, we have chosen to use paramagnetic labels targeting cysteine residues to monitor potential conformational changes by electron paramagnetic resonance (EPR). Given the level of conservation of the cysteines in ACCO from different plants, this work provides an essential basis for the use of cysteine as probe-anchoring residues.

ACS Style

Sybille Tachon; Eugénie Fournier; Christophe Decroos; Pascal Mansuelle; Emilien Etienne; Marc Maresca; Marlène Martinho; Valérie Belle; Thierry Tron; Ariane Jalila Simaan. Chemical Modification of 1-Aminocyclopropane Carboxylic Acid (ACC) Oxidase: Cysteine Mutational Analysis, Characterization, and Bioconjugation with a Nitroxide Spin Label. Molecular Biotechnology 2019, 61, 650 -662.

AMA Style

Sybille Tachon, Eugénie Fournier, Christophe Decroos, Pascal Mansuelle, Emilien Etienne, Marc Maresca, Marlène Martinho, Valérie Belle, Thierry Tron, Ariane Jalila Simaan. Chemical Modification of 1-Aminocyclopropane Carboxylic Acid (ACC) Oxidase: Cysteine Mutational Analysis, Characterization, and Bioconjugation with a Nitroxide Spin Label. Molecular Biotechnology. 2019; 61 (9):650-662.

Chicago/Turabian Style

Sybille Tachon; Eugénie Fournier; Christophe Decroos; Pascal Mansuelle; Emilien Etienne; Marc Maresca; Marlène Martinho; Valérie Belle; Thierry Tron; Ariane Jalila Simaan. 2019. "Chemical Modification of 1-Aminocyclopropane Carboxylic Acid (ACC) Oxidase: Cysteine Mutational Analysis, Characterization, and Bioconjugation with a Nitroxide Spin Label." Molecular Biotechnology 61, no. 9: 650-662.

Original research article
Published: 07 June 2019 in Frontiers in Microbiology
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The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin. In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized. But yet, considering the fact that uncultured species predominate in the human gut microbiota, these biochemical data are far from exhaustive. In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans. First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates. The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase. Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening. This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus. In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones. Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery. These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.

ACS Style

Elisabeth Laville; Josette Perrier; Nada Bejar; Marc Maresca; Jeremy Esque; Alexandra S. Tauzin; Emna Bouhajja; Marion Leclerc; Elodie Drula; Bernard Henrissat; Stephane Berdah; Eric Di Pasquale; Patrick Robe; Gabrielle Potocki-Veronese. Investigating Host Microbiota Relationships Through Functional Metagenomics. Frontiers in Microbiology 2019, 10, 1286 .

AMA Style

Elisabeth Laville, Josette Perrier, Nada Bejar, Marc Maresca, Jeremy Esque, Alexandra S. Tauzin, Emna Bouhajja, Marion Leclerc, Elodie Drula, Bernard Henrissat, Stephane Berdah, Eric Di Pasquale, Patrick Robe, Gabrielle Potocki-Veronese. Investigating Host Microbiota Relationships Through Functional Metagenomics. Frontiers in Microbiology. 2019; 10 ():1286.

Chicago/Turabian Style

Elisabeth Laville; Josette Perrier; Nada Bejar; Marc Maresca; Jeremy Esque; Alexandra S. Tauzin; Emna Bouhajja; Marion Leclerc; Elodie Drula; Bernard Henrissat; Stephane Berdah; Eric Di Pasquale; Patrick Robe; Gabrielle Potocki-Veronese. 2019. "Investigating Host Microbiota Relationships Through Functional Metagenomics." Frontiers in Microbiology 10, no. : 1286.

Original research article
Published: 29 March 2019 in Frontiers in Immunology
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Strong tight junctions and curtailed inflammatory responses under stressful conditions are key for optimal digestive health. Bacillus-based probiotics are increasingly being used to maintain broilers' health, but their mode of action is often not well-defined. In the present study we used Caco-2 cells as a model for intestinal epithelia and assessed the effect of three Bacillus-based probiotics on intestinal barrier function and intestinal inflammation. Experimental results showed that one of the three tested strains, Bs 29784, significantly reinforced intestinal barrier integrity under basal conditions through an up-regulation of the expression of tight junction's proteins, whereas the others had no or detrimental effects. When Caco-2 cells were pre-treated with Bacillus subtilis strains, the subsequent IL-8 release to various pro-inflammatory signals (IL-1β, deoxynivalenol, or flagellin) was blunted compared to cells that had not been pretreated, but to a different extent depending on the strain of Bacillus used. Bs 29784, was able to significantly decrease IL-8 production in all stressed conditions tested. Mechanistically, Bs 29784 appeared to limit nuclear translocation of NF-κB during IL-1β exposure by preventing IκB degradation. The effects of Bs 29784 were observed independently with supernatant and cells but in a lesser extent than with the combination, indicating that they can thus likely be attributed to both secreted metabolites and cell-associated compounds. Moreover, under inflammatory conditions, Bs 29784 significantly reduced the upregulation of iNOS protein levels further underlining its intestinal anti-inflammatory potential. Our data show that Bacillus-based probiotics may indeed improve digestive health by strengthening intestinal barrier and limiting inflammatory responses and that these properties are strain-dependent.

ACS Style

Lamya Rhayat; Marc Maresca; Cendrine Nicoletti; Josette Perrier; Karoline Sidelmann Brinch; Sonja Christian; Estelle Devillard; Erik Eckhardt. Effect of Bacillus subtilis Strains on Intestinal Barrier Function and Inflammatory Response. Frontiers in Immunology 2019, 10, 1 .

AMA Style

Lamya Rhayat, Marc Maresca, Cendrine Nicoletti, Josette Perrier, Karoline Sidelmann Brinch, Sonja Christian, Estelle Devillard, Erik Eckhardt. Effect of Bacillus subtilis Strains on Intestinal Barrier Function and Inflammatory Response. Frontiers in Immunology. 2019; 10 ():1.

Chicago/Turabian Style

Lamya Rhayat; Marc Maresca; Cendrine Nicoletti; Josette Perrier; Karoline Sidelmann Brinch; Sonja Christian; Estelle Devillard; Erik Eckhardt. 2019. "Effect of Bacillus subtilis Strains on Intestinal Barrier Function and Inflammatory Response." Frontiers in Immunology 10, no. : 1.

Preprint
Published: 13 March 2019
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Herein we report the identification and characterisation of two linear antimicrobial peptides (AMPs), HG2 and HG4, with activity against a wide range of multidrug resistant (MDR) bacteria, especially methicillin resistantStaphylococcus aureus(MRSA) strains, a highly problematic group of Gram-positive bacteria in the hospital and community environment. To identify the novel AMPs presented here, we employed the classifier model design, a feature extraction method using molecular descriptors for amino acids for the analysis, visualization, and interpretation of AMP activities from a rumen metagenomic dataset. This allowed for thein silicodiscrimination of active and inactive peptides in order to define a small number of promising novel lead AMP test candidates for chemical synthesis and experimental evaluation.In vitrodata suggest that the chosen AMPs are fast acting, show strong biofilm inhibition and dispersal activity and are efficacious in anin vivomodel of MRSA USA300 infection, whilst showing little toxicity to human erythrocytes and human primary cell linesex vivo. Observations from biophysical AMP-lipid-interactions and electron microscopy suggest that the newly identified peptides interact with the cell membrane and may be involved in the inhibition of other cellular processes. Amphiphilic conformations associated with membrane disruption are also observed in 3D molecular modelling of the peptides. HG2 and HG4 both preferentially bind to MRSA total lipids rather than with human cell lipids indicating that HG4 may form superior templates for safer therapeutic candidates for MDR bacterial infections.Author SummaryWe are losing our ability to treat multidrug resistant (MDR) bacteria, otherwise known as superbugs. This poses a serious global threat to human health as bacteria are increasingly acquiring resistance to antibiotics. There is therefore urgent need to intensify our efforts to develop new safer alternative drug candidates. We emphasise the usefulness of complementing wet-lab andin silicotechniques for the rapid identification of new drug candidates from environmental samples, especially antimicrobial peptides (AMPs). HG2 and HG4, the AMPs identified in our study show promise as effective therapies for the treatment of methicillin resistantStaphylococcus aureusinfections bothin vitroandin vivowhilst having little cytotoxicity against human primary cells, a step forward in the fight against MDR infections.

ACS Style

Linda Boniface Oyama; Hamza Olleik; Ana Carolina Nery Teixeira; Matheus M Guidini; James A Pickup; Alan R Cookson; Hannah Vallin; Toby Wilkinson; Denise Bazzolli; Jennifer Richards; Mandy Wootton; Ralf Mikut; Kai Hilpert; Marc Maresca; Josette Perrier; Matthias Hess; Hilario C Mantovani; Narcis Fernandez-Fuentes; Christopher J Creevey; Sharon A Huws. In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus. 2019, 577221 .

AMA Style

Linda Boniface Oyama, Hamza Olleik, Ana Carolina Nery Teixeira, Matheus M Guidini, James A Pickup, Alan R Cookson, Hannah Vallin, Toby Wilkinson, Denise Bazzolli, Jennifer Richards, Mandy Wootton, Ralf Mikut, Kai Hilpert, Marc Maresca, Josette Perrier, Matthias Hess, Hilario C Mantovani, Narcis Fernandez-Fuentes, Christopher J Creevey, Sharon A Huws. In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus. . 2019; ():577221.

Chicago/Turabian Style

Linda Boniface Oyama; Hamza Olleik; Ana Carolina Nery Teixeira; Matheus M Guidini; James A Pickup; Alan R Cookson; Hannah Vallin; Toby Wilkinson; Denise Bazzolli; Jennifer Richards; Mandy Wootton; Ralf Mikut; Kai Hilpert; Marc Maresca; Josette Perrier; Matthias Hess; Hilario C Mantovani; Narcis Fernandez-Fuentes; Christopher J Creevey; Sharon A Huws. 2019. "In silicoidentification of novel peptides with antibacterial activity against multidrug resistantStaphylococcus aureus." , no. : 577221.

Organ toxicity and mechanisms
Published: 11 March 2019 in Archives of Toxicology
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Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC50 of 361, 387 and 243 nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.

ACS Style

Fabien Graziani; Philippe Pinton; Hamza Olleik; Ange Pujol; Cendrine Nicoletti; Mehdi Sicre; Nathalie Quinson; El Hassan Ajandouz; Josette Perrier; Eric Di Pasquale; Isabelle P. Oswald; Marc Maresca. Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells. Archives of Toxicology 2019, 93, 1039 -1049.

AMA Style

Fabien Graziani, Philippe Pinton, Hamza Olleik, Ange Pujol, Cendrine Nicoletti, Mehdi Sicre, Nathalie Quinson, El Hassan Ajandouz, Josette Perrier, Eric Di Pasquale, Isabelle P. Oswald, Marc Maresca. Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells. Archives of Toxicology. 2019; 93 (4):1039-1049.

Chicago/Turabian Style

Fabien Graziani; Philippe Pinton; Hamza Olleik; Ange Pujol; Cendrine Nicoletti; Mehdi Sicre; Nathalie Quinson; El Hassan Ajandouz; Josette Perrier; Eric Di Pasquale; Isabelle P. Oswald; Marc Maresca. 2019. "Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells." Archives of Toxicology 93, no. 4: 1039-1049.

Journal article
Published: 01 March 2019 in Access Microbiology
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ACS Style

Linda Oyama; Hamza Olleik; Ana Carolina Nery Teixeira; Matheus M Guidini; James A Pickup; Alan R Cookson; Hannah Vallin; Toby Wilkinson; Denise Bazzolli; Jennifer Richards; Mandy Wootton; Ralf Mikut; Kai Hilpert; Marc Maresca; Josette Perrier; Matthias Hess; Hilario C Mantovani; Narcis Fernandez-Fuentes; Christopher J Creevey; Sharon A Huws. In silico identification of two novel antimicrobial peptides with antibacterial activity against multi-drug resistant Staphylococcus aureus. Access Microbiology 2019, 1, 1 .

AMA Style

Linda Oyama, Hamza Olleik, Ana Carolina Nery Teixeira, Matheus M Guidini, James A Pickup, Alan R Cookson, Hannah Vallin, Toby Wilkinson, Denise Bazzolli, Jennifer Richards, Mandy Wootton, Ralf Mikut, Kai Hilpert, Marc Maresca, Josette Perrier, Matthias Hess, Hilario C Mantovani, Narcis Fernandez-Fuentes, Christopher J Creevey, Sharon A Huws. In silico identification of two novel antimicrobial peptides with antibacterial activity against multi-drug resistant Staphylococcus aureus. Access Microbiology. 2019; 1 (1A):1.

Chicago/Turabian Style

Linda Oyama; Hamza Olleik; Ana Carolina Nery Teixeira; Matheus M Guidini; James A Pickup; Alan R Cookson; Hannah Vallin; Toby Wilkinson; Denise Bazzolli; Jennifer Richards; Mandy Wootton; Ralf Mikut; Kai Hilpert; Marc Maresca; Josette Perrier; Matthias Hess; Hilario C Mantovani; Narcis Fernandez-Fuentes; Christopher J Creevey; Sharon A Huws. 2019. "In silico identification of two novel antimicrobial peptides with antibacterial activity against multi-drug resistant Staphylococcus aureus." Access Microbiology 1, no. 1A: 1.