Purchase this article with an account.
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)
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.
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.
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
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