New insights in Escherichia coli colistin resistant strains isolated from Argentina

MATURANA P; MARTINEZ, M; FACCONE, D; SEMORILE, L; MAFFIA, P; HOLLMANN A

Virtual

Congreso; Primeras Jornadas Virtuales SAB 2020; 2020

Sociedad Argentina de Biofisica

Colistin is an antibiotic (polymyxin E) that has in recent years re-emerged as an optionfor the treatment of multi-drug resistant bacteria. This re-introduction resulted in theappearance of new colistin-resistant bacteria, usually caused by LPS modifications. Oneof these resistance phenotypes is mediated by a plasmid carrying the mcr-1 gene thatencodes, a phosphoethanolamine transferase, that attached phosphoethanolaminemoiety to the lipid A, resulting in a more cationic LPS that impairs the colistinattachment. Recently in Argentina, Escherichia coli resistant isolates with MCR-1 plasmidwas been detected. In this context, we proposed to assess the effect of surface chargemodifications induced by carrying MCR-1 plasmid and its impact on the resulting colistinresistance in two clinical E. coli isolates. Using zeta potential, we confirmed the reductionof negative charge exposure on both resistance isolates compared to the susceptiblereference strain. Furthermore, the effects on the phosphoethanolamine transferaseinactivation, by removal of zinc through the inclusion of EDTA, were also evaluated byMIC determination and Zeta Potential. Finally, through permeabilization and live/deadfluorescence assays, we were able to correlate this reduction in charge exposure with theextent of damage to the bacterial membrane. The fact that the zeta potential matcheswith the membrane permeabilization and MIC results on both clinical isolates couldsuggest a partial substitution of lipid A that reduces the possible colistin site ofattachment, or that the less negative zeta potential reduces the electrostatic force thatdrives the first step in colistin attachment, resulting in weaker interaction of colistin withthe bacterial surface. Finally, due to this surface charge modification is plasmid-encoded,represents an important concern for the possibility of horizontal transference and theimpact on other cationic antimicrobial compounds as many AMPs.