Combined Efficacy of an Antimicrobial Cationic Peptide Polymer with Conventional Antibiotics to Combat Multidrug-Resistant Pathogens.

ACS Infectious Diseases
Kishore Reddy ThappetaKimberly A Kline

Abstract

Antibiotic-resistant infections are predicted to kill 10 million people worldwide per year by 2050 and to cost the global economy 100 trillion USD. Novel approaches and alternatives to conventional antibiotics are urgently required to combat antimicrobial resistance. We have synthesized a chitosan-based oligolysine antimicrobial peptide, CSM5-K5 (where CSM denotes chitosan monomer repeat units and K denotes lysine amino acid repeat units), that targets multidrug-resistant (MDR) bacterial species. Here, we show that CSM5-K5 exhibits rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA), MDR Escherichia coli, and vancomycin-resistant Enterococcus faecalis (VRE). Combinatorial therapy of CSM5-K5 with antibiotics to which each organism is otherwise resistant restores sensitivity to the conventional antibiotic. CSM5-K5 alone significantly reduced preformed bacterial biofilm by 2-4 orders of magnitude and, in combination with conventional antibiotics, reduced preformed biofilm by more than 2-3 orders of magnitude at subinhibitory concentrations. Moreover, using a mouse excisional wound infection model, CSM5-K5 treatment reduced bacterial burdens by 1-3 orders of magnitude and acted synergistically wit...Continue Reading

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Citations

Jan 6, 2021·Advanced Drug Delivery Reviews·Yunjiang JiangJianjun Cheng
Jan 13, 2021·ACS Infectious Diseases·Rashin Namivandi-ZangenehCyrille Boyer
Nov 19, 2020·International Journal of Molecular Sciences·Kishore Reddy Venkata ThappetaSiew Bee Ng
Mar 27, 2021·Microbial Biotechnology·Thomas K Wood
Apr 20, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xi-Le HuDaijie Chen
Jun 8, 2021·Biomaterials Science·Zixian CuiRachel A Letteri
Aug 2, 2021·Current Opinion in Microbiology·Ronni A G da SilvaKimberly A Kline
Jan 7, 2021·ACS Applied Materials & Interfaces·Zhangyong SiMary B Chan-Park

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