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Pathog Dis. 2015 Nov;73(8):ftv053. doi: 10.1093/femspd/ftv053. Epub 2015 Jul 29.

Site-specific activity of the acyltransferases HtrB1 and HtrB2 in Pseudomonas aeruginosa lipid A biosynthesis.

Author information

1
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
2
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA 98195, USA.
3
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, WA 98195, USA Department of Pediatrics, Massachusetts General Hospital, Boston, MA 20114, USA.
4
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA rkernst@umaryland.edu.

Abstract

Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative pathogen associated with nosocomial infections, acute infections and chronic lung infections in patients with cystic fibrosis. The ability of PA to cause infection can be attributed to its ability to adapt to a multitude of environments. Modification of the lipid A portion of lipopolysaccharide (LPS) is a vital mechanism Gram-negative pathogens use to remodel the outer membrane in response to environmental stimuli. Lipid A, the endotoxic moiety of LPS, is the major component of the outer leaflet of the outer membrane of Gram-negative bacteria making it a critical factor for bacterial adaptation. One way PA modifies its lipid A is through the addition of laurate and 2-hydroxylaurate. This secondary or late acylation is carried out by the acyltransferase, HtrB (LpxL). Analysis of the PA genome revealed the presence of two htrB homologs, PA0011 (htrB1) and PA3242 (htrB2). In this study, we were able to show that each gene identified is responsible for site-specific modification of lipid A. Additionally, deletions of either gene altered resistance to specific classes of antibiotics, cationic antimicrobial peptides and increased membrane permeability suggesting a role for these enzymes in maintaining optimal membrane organization and integrity.

KEYWORDS:

HtrB; LPS; Pseudomonas aeruginosa; acyltransferase; lipid A; membrane remodeling

PMID:
26223882
PMCID:
PMC4626592
DOI:
10.1093/femspd/ftv053
[Indexed for MEDLINE]
Free PMC Article

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