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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.
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 StyleClarisse 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 StyleClarisse 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.
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.
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 StyleMohammad 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 StyleMohammad 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.
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.
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 StyleHunain 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 StyleHunain 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.
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.
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 StyleClarisse 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 StyleClarisse 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.
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.
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 StyleHamza 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 StyleHamza 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.
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.
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 StyleHamza 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 StyleHamza 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.
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.
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 StyleSteve 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 StyleSteve 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.
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.
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 StyleHamza 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 StyleHamza 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.
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.
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 StyleRenato 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 StyleRenato 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.
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.
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 StyleLinda 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 StyleLinda 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.
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 StyleLinda 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 StyleLinda 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.