The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens

Sara, Manjulatha; Yasir, Muhammad; Kalaiselvan, Parthasarathi; Hui, Alex; Kuppusamy, Rajesh; Kumar, Naresh; Chakraborty, Sudip; Yu, Tsz Tin; Wong, Edgar H. H.; Molchanova, Natalia; Jenssen, Håvard; Lin, Jennifer S.; Barron, Annelise E.; Willcox, Mark

doi:10.1016/j.clae.2024.102124

The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens

Journal Article · Fri Feb 09 00:00:00 EST 2024 · Contact Lens and Anterior Eye

DOI:https://doi.org/10.1016/j.clae.2024.102124· OSTI ID:2294152

Sara, Manjulatha ^[1]; Yasir, Muhammad ^[1]; Kalaiselvan, Parthasarathi ^[1]; Hui, Alex ^[2]; Kuppusamy, Rajesh ^[1]; Kumar, Naresh ^[1]; Chakraborty, Sudip ^[1]; Yu, Tsz Tin ^[1]; Wong, Edgar H. H. ^[1]; Molchanova, Natalia ^[3]; Jenssen, Håvard ^[4]; Lin, Jennifer S. ^[5]; Barron, Annelise E. ^[5]; ^[1]

Univ. of New South Wales, Sydney, NSW (Australia)
Univ. of New South Wales, Sydney, NSW (Australia); Univ. of Waterloo, ON (Canada)
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Molecular Foundry
Roskilde University (Denmark)
Stanford Univ., CA (United States)

Background: Ocular infections caused by antibiotic-resistant pathogens can result in partial or complete vision loss. The development of pan-resistant microbial strains poses a significant challenge for clinicians as there are limited antimicrobial options available. Synthetic peptoids, which are sequence-specific oligo-N-substituted glycines, offer potential as alternative antimicrobial agents to target multidrug-resistant bacteria. Methods: The antimicrobial activity of synthesised peptoids against multidrug-resistant (MDR) ocular pathogens was evaluated using the microbroth dilution method. Hemolytic propensity was assessed using mammalian erythrocytes. Peptoids were also incubated with proteolytic enzymes, after which their minimum inhibitory activity against bacteria was re-evaluated. Results: Several alkylated and brominated peptoids showed good inhibitory activity against multidrug-resistant Pseudomonas aeruginosa strains at concentrations of ≤15 μg mL^-1 (≤12 µM). Similarly, most brominated compounds inhibited the growth of methicillin-resistant Staphylococcus aureus at 1.9 to 15 μg mL^-1 (12 µM). The N-terminally alkylated peptoids caused less toxicity to erythrocytes. The peptoid denoted as TM5 had a high therapeutic index, being non-toxic to either erythrocytes or corneal epithelial cells, even at 15 to 22 times its MIC. Additionally, the peptoids were resistant to protease activity. Conclusions: Peptoids studied here demonstrated potent activity against various multidrug-resistant ocular pathogens. Their properties make them promising candidates for controlling vision-related morbidity associated with eye infections by antibiotic-resistant strains.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Health and Medical Research Council; National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2294152

Alternate ID(s):: OSTI ID: 2474870

Journal Information:: Contact Lens and Anterior Eye, Journal Name: Contact Lens and Anterior Eye Journal Issue: 2 Vol. 47; ISSN 1367-0484

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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