Antimicrobial Activity of Two New Peptides (S2-P082090 and S5-P082090) Against Gram-Positive and Negative Bacteria: Comparison with Omiganan (OMI)

MAFFIA PAULO CESAR; FACCONE, DIEGO; VELIZ, OMAR; BOGADO, BETIANA; SEMORILE, LILIANA; CORSO, ALEJANDRA

San Francisco

Congreso; Interscience Conference on Antimicrobial Agents and Chemotherapy; 2012

American Society for Microbiology

Background. The cationic antimicrobial peptides have been shown to have a broad spectrum of antibacterial activity, including gram-positive and gram-negative. These peptides act on the bacterial membrane, permeabilising it selectively, but not targeting a receptor, unlike traditional antibiotics that interact with specific microbial targets. Omiganan Pentahydrochloride ® (MBI 226) is a synthetic cationic peptide analogue to indolicidin with activity against bacteria and yeasts and is currently in clinical trials for topical use. The antimicrobial activity of two new in silico designed peptides was evaluated against a clinical bacteria panel. Methods. Antimicrobial activity of peptides S2-P082090 and S5-P082090 was investigated in vitro using Omiganan® (OMI) as comparator. MIC was determined by CLSI broth microdilution method (M07-A8) using cation-adjusted Mueller-Hinton broth. We included 79 previously characterized isolates collected at the National Reference Laboratory (INEI) with different mechanisms of resistance: 38 GP (WT, vanA, vanB, vanC, mecA, ermA, ermC, msrA, lnuA) and 41 GN (tem-1, cmy, cit, shv-1, ctx-m-2, per-2, ges-1/3, veb-1, oxa-9, oxa-23, oxa-58, vim-11, imp-1/13/16, spm-1, kpc-2). Additionally P. aeruginosa ATCC27853, E. coli ATCC25922, S. aureus ATCC29213 and E. faecalis ATCC51299 and ATCC29212 were included as reference strains. Results. MIC50/MIC90/Range Organism (no. Isolates) S2 S5 OMI S. aureus (12) 32/64/32-128 64/64/32-64 32/64/32-128 CNS (12) 8/16/4-32 8/8/4-16 8/8/4-16 E. faecalis (6) 128/256/128-256 128/256/128-256 128/256/128-256 E. non-faecalis (11) 16/16/8-32 16/16/8-16 16/16/4-16 K. pneumoniae (12) 32/64/8-128 32/64/8-128 128/1024/32-1024 E. coli (9) 32/64/4-64 32/64/16-128 64/64/32-64 P. aeruginosa (12) 64/64/64 64/64/32-128 512/512/128-512 A. baumannii (10) 16/32/4-32 8/32/4-32 64/64/16-128 Conclusion. S2-P082090 and S5-P082090 peptides demonstrated comparable MIC50/MIC90/MIC range between them. S2-P082090 and S5-P082090 peptides showed similar activity than OMI against GP isolates but higher against GN. Main differences were observed in K. pneumoniae and P. aeruginosa with MIC 3-4 dilution lower than OMI.