Antimicrobial peptides with symmetric structures against multidrug-resistant bacteria while alleviating antimicrobial resistance

Infections by multidrug-resistant bacteria are becoming a major healthcare emergence with millions of reported cases every year and an increasing incidence of deaths. An advanced diagnostic platform able to directly detect and identify antimicrobial resistance in a faster way than conventional techniques could help in the adoption of early and accurate therapeutic interventions, limiting the actual negative impact on patient outcomes. With this objective, we have developed a new biosensor methodology using an ultrasensitive nanophotonic bimodal waveguide interferometer (BiMW), which allows a rapid and direct detection, without amplification, of two prevalent and clinically relevant Gram-negative antimicrobial resistance encoding sequences: the extended-spectrum betalactamase-encoding gene blaCTX-M-15 and the carbapenemase-encoding gene blaNDM-5 We demonstrate the extreme sensitivity and specificity of our biosensor methodology for the detection of both gene sequences. Our results show that the BiMW biosensor can be employed as an ultrasensitive (attomolar level) and specific diagnostic tool for rapidly (less than 30 min) identifying drug resistance. The BiMW nanobiosensor holds great promise as a powerful tool for the control and management of healthcare-associated infections by multidrug-resistant bacteria.

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Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

Pharmaceutics ◽

10.3390/pharmaceutics12060501 ◽

2020 ◽

Vol 12 (6) ◽

pp. 501 ◽

Cited By ~ 3

Author(s):

Berthony Deslouches ◽

Ronald C. Montelaro ◽

Ken L. Urish ◽

Yuanpu P. Di

Keyword(s):

Antimicrobial Peptides ◽

De Novo ◽

Multidrug Resistant ◽

Clinical Development ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Health Crisis ◽

Test Conditions ◽

Reduced Activity

The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

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Bacteriocins, Antimicrobial Peptides from Bacterial Origin: Overview of Their Biology and Their Impact against Multidrug-Resistant Bacteria

Microorganisms ◽

10.3390/microorganisms8050639 ◽

2020 ◽

Vol 8 (5) ◽

pp. 639 ◽

Cited By ~ 13

Author(s):

Alexis Simons ◽

Kamel Alhanout ◽

Raphaël E. Duval

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Multidrug Resistant Bacteria ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Further Development

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.

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Antimicrobial peptides conjugated with fatty acids on the side chain of D-amino acid promises antimicrobial potency against multidrug-resistant bacteria

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2019.105123 ◽

2020 ◽

Vol 141 ◽

pp. 105123 ◽

Cited By ~ 16

Author(s):

Chao Zhong ◽

Ningyi Zhu ◽

Yuewen Zhu ◽

Tianqi Liu ◽

Sanhu Gou ◽

...

Keyword(s):

Fatty Acids ◽

Amino Acid ◽

Antimicrobial Peptides ◽

Multidrug Resistant ◽

Side Chain ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Antimicrobial Potency

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Two Hits Are Better than One: Membrane-Active and DNA Binding-Related Double-Action Mechanism of NK-18, a Novel Antimicrobial Peptide Derived from Mammalian NK-Lysin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01619-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 220-228 ◽

Cited By ~ 61

Author(s):

Jiexi Yan ◽

Kairong Wang ◽

Wen Dang ◽

Ru Chen ◽

Junqiu Xie ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Cytotoxic T Cells ◽

Multidrug Resistant ◽

Chemotherapeutic Agents ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Content Type ◽

New Strategy ◽

Conventional Antibiotics ◽

Double Targets

ABSTRACTThe extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NK-Lysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity againstEscherichia coliandStaphylococcus aureus. According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.

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