The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens

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

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

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.
OriginalsprogEngelsk
Artikelnummer102124
TidsskriftContact Lens and Anterior Eye
Vol/bind47
Udgave nummer2
Antal sider10
ISSN1367-0484
DOI
StatusUdgivet - apr. 2024

Finansiering

Funding Information: AEB thanks the NIH for funding this work with a Director's Pioneer Award, grant # 1DP1 OD029517. AEB also acknowledges funding from Stanford University's Discovery Innovation Fund, the Cisco University Research Program Fund, and the Silicon Valley Community Foundation, Stephen Pearse, and Dr. James J. Truchard and the Truchard Foundation.

Emneord

  • Antimicrobial peptoids
  • Keratitis
  • Pseudomonas aeruginosa
  • Staphylococcus aureus

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