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Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.

Abstract：

:Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A. baumannii clinical isolates that acquired colistin resistance due to mutations in lpxA, lpxC and lpxD as well as their colistin-susceptible counterparts. A dramatic increase in antibiotic susceptibility (≥16-fold increase) was observed upon LPS loss for azithromycin, rifampicin and vancomycin, whereas a moderate increase in susceptibility was seen for amikacin, ceftazidime, imipenem, cefepime and meropenem. Importantly, concentrations ranging from 8 mg/L to 32 mg/L of the six AMPs were able to reduce bacterial viability by ≥3 log10 in growth curve assays. We also demonstrate that colistin resistance results in partial colistin dependence for growth in LPS-deficient strains containing mutations in lpxA, lpxC and lpxD, but not when colistin resistance occurs via LPS modification due to mutations in the PmrA/B two-component system. The results of this study indicate that loss of LPS expression results in collateral sensitivity to azithromycin, rifampicin and vancomycin, and that the six AMPs tested retain activity against LPS-deficient strains, indicating that these antibiotics may be viable treatment options for infections caused by these strains.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

García-Quintanilla M,Carretero-Ledesma M,Moreno-Martínez P,Martín-Peña R,Pachón J,McConnell MJ

doi

10.1016/j.ijantimicag.2015.07.017

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

696-702

issue

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(15)00287-3

journal_volume

pub_type

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Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.