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Combined efficacy of a novel antimicrobial cationic peptide polymer with conventional antibiotics to combat multi-drug resistant pathogens

Kishore Reddy Thappeta, Yogesh Shankar Vikhe, Adeline Mei Hui Yong, Mary B. Chan Park, View ORCID ProfileKimberly A. Kline
doi: https://doi.org/10.1101/735217
Kishore Reddy Thappeta
1Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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Yogesh Shankar Vikhe
2School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459
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Adeline Mei Hui Yong
1Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
3School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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Mary B. Chan Park
2School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459
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Kimberly A. Kline
1Singapore Centre for Environmental Life Science Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
3School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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  • ORCID record for Kimberly A. Kline
  • For correspondence: kkline@ntu.edu.sg
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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, which 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 pre-formed bacterial biofilm by two-four orders of magnitude and, in combination with traditional antibiotics, reduced pre-formed biofilm by more than two-three orders of magnitude at sub inhibitory concentrations. Moreover, using a mouse excisional wound infection model, CSM5-K5 treatment reduced bacterial burdens by one to three orders of magnitude, and acted synergistically with vancomycin and tetracycline to clear VRE and MDR E. coli, respectively. Importantly, little to no resistance against CSM5-K5 arose for any of the three MDR bacteria during 15 days of serial passage. This work demonstrates the feasibility and benefits of using this synthetic cationic peptide as alternative to, or in combination with, traditional antibiotics to treat infections caused by MDR bacteria.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 14, 2019.
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Combined efficacy of a novel antimicrobial cationic peptide polymer with conventional antibiotics to combat multi-drug resistant pathogens
Kishore Reddy Thappeta, Yogesh Shankar Vikhe, Adeline Mei Hui Yong, Mary B. Chan Park, Kimberly A. Kline
bioRxiv 735217; doi: https://doi.org/10.1101/735217
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Combined efficacy of a novel antimicrobial cationic peptide polymer with conventional antibiotics to combat multi-drug resistant pathogens
Kishore Reddy Thappeta, Yogesh Shankar Vikhe, Adeline Mei Hui Yong, Mary B. Chan Park, Kimberly A. Kline
bioRxiv 735217; doi: https://doi.org/10.1101/735217

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