Colistin heteroresistance in Enterobacter cloacae is regulated by PhoPQ-dependent 4-amino-4-deoxy-l-arabinose addition to lipid A - Archive ouverte HAL Access content directly
Journal Articles Molecular Microbiology Year : 2019

Colistin heteroresistance in Enterobacter cloacae is regulated by PhoPQ-dependent 4-amino-4-deoxy-l-arabinose addition to lipid A

(1) , (2) , (1) , (3, 4) , (5, 6) , (2) , (1)
1
2
3
4
5
6

Abstract

The Enterobacter cloacae complex (ECC) consists of closely-related bacteria commonly associated with the human microbiota. ECC are increasingly isolated from healthcare-associated infections, demonstrating that these Enterobacteriaceae are emerging nosocomial pathogens. ECC can rapidly acquire multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the highly conserved lipid A component of the Gram-negative outer membrane. Many Enterobacteriaceae fortify their outer membrane with cationic amine-containing moieties to prevent CAMP binding, which can lead to cell lysis. The PmrAB two-component system (TCS) directly activates 4-amino-4-deoxy-l-arabinose (l-Ara4N) biosynthesis to result in cationic amine moiety addition to lipid A in many Enterobacteriaceae such as E. coli and Salmonella. In contrast, PmrAB is dispensable for CAMP resistance in E. cloacae. Interestingly, some ECC clusters exhibit colistin heteroresistance, where a subpopulation of cells exhibit clinically significant resistance levels compared to the majority population. We demonstrate that E. cloacae lipid A is modified with l-Ara4N to induce CAMP heteroresistance and the regulatory mechanism is independent of the PmrAB TCS. Instead, PhoP binds to the arnB promoter to induce l-Ara4N biosynthesis and PmrAB-independent addition to the lipid A disaccharolipid. Therefore, PhoPQ contributes to regulation of CAMP heteroresistance in some ECC clusters.
Fichier principal
Vignette du fichier
Kang et al-Colistin heteroresistance in Enterobacter cloacae is regulated by.pdf (1.39 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

hal-02087955 , version 1 (13-05-2019)

Identifiers

Cite

Katie N Kang, Dustin R Klein, Misha I Kazi, Francois Guerin, Vincent Cattoir, et al.. Colistin heteroresistance in Enterobacter cloacae is regulated by PhoPQ-dependent 4-amino-4-deoxy-l-arabinose addition to lipid A. Molecular Microbiology, 2019, 111 (6), pp.1604-1616. ⟨10.1111/mmi.14240⟩. ⟨hal-02087955⟩
134 View
206 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More