June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Cylam based antibacterial molecule eradicates gram negative superbugs with potent efficacy human corneal infection isolates
Author Affiliations & Notes
  • Prashant Garg
    KAR Campus, L V Prasad Eye Institute, Hyderabad, ANDHRA PRADESH, India
  • Mohini M Konai
    Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research,, Bangalore, India
  • Khatija Tabbasum
    L V Prasad Eye Institute, Hyderabad, Hyderabad, India
    Brien Holden eye research center, Hyderabad, India
  • Jayanta Haldar
    Antimicrobial Research Laboratory, New Chemistry Unit and School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research,, Bangalore, India
  • Footnotes
    Commercial Relationships   Prashant Garg, None; Mohini Konai, None; Khatija Tabbasum, None; Jayanta Haldar, None
  • Footnotes
    Support  Department of biotechnology, Government of India
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3260. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Prashant Garg, Mohini M Konai, Khatija Tabbasum, Jayanta Haldar; Cylam based antibacterial molecule eradicates gram negative superbugs with potent efficacy human corneal infection isolates. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3260.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : The catastrophic growth in the antibiotic resistance has become a serious concern toward public health. There is an urgent need to develop an antibacterial solution that is not only effective against drug resistant pathogens but also has low propensity for the development of resistance. We report the activity of a novel cyclam based lipopeptide antibacterial molecule against corneal ulcer pathogens.

Methods : The test drug was developed by incorporation of long chain fatty acid to cyclam backbone. To mimic lipopeptide, the hydrophobic amino-acid were introduced in the design. The antibacterial activity of the compounds (CAM 1-8) was then tested against drug-sensitive strains of critical Gram-negative bacteria. The most active compound of the series was evaluated (time kill kinetics) against drug-resistant gram positive (MRSA) and negative (A. Baumannii, P. Aeruginosa, E. Coli and K. Pneumoniae) clinical isolates in in-vitro and ex-vivo cornea infection models. The compound was assessed for its propensity to develop resistance and toxicity.

Results : The leucine analogue (CAM-8) had the best activity against all drug sensitive and resistant bacteria (MICCAM-8 = 2-8 µg/mL). CAM-8 was found to be rapidly bactericidal and exhibited ~5-6 log reduction both against planktonic and stationary phase bacteria whereas the antibiotics tetracycline and meropenem were ineffective. The compound retained activity (MIC in the range of 4-16 µg/mL) in the presence of 50% human plasma confirming immunity against protease degradation and did not show significant hemolysis even at 32 µg/mL and toxicity against other mammalian cells. All four critical Gram-negative bacteria showed negligible ability to develop resistance against the test compound CAM-8

Conclusions : The results clearly portrayed that CAM-8 was effective in the treatment of human corneal infection model (Fig. 3F). It not only reduced the bacterial burden for ATCC strain, but was also effective against drug-resistant clinical isolate obtained from corneal ulcer cases.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×