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Proc Natl Acad Sci U S A. 2012 May 29;109(22):8716-21. doi: 10.1073/pnas.1202908109. Epub 2012 May 14.

LPS remodeling is an evolved survival strategy for bacteria.

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  • 1State Key Laboratory of Food Science and Technology, School of Biotechnology, Jiangnan University, Wuxi 214211, China.

Erratum in

  • Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13877.

Abstract

Maintenance of membrane function is essential and regulated at the genomic, transcriptional, and translational levels. Bacterial pathogens have a variety of mechanisms to adapt their membrane in response to transmission between environment, vector, and human host. Using a well-characterized model of lipid A diversification (Francisella), we demonstrate temperature-regulated membrane remodeling directed by multiple alleles of the lipid A-modifying N-acyltransferase enzyme, LpxD. Structural analysis of the lipid A at environmental and host temperatures revealed that the LpxD1 enzyme added a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme added a 3-OH C16 acyl group at 18 °C (environment). Mutational analysis of either of the individual Francisella lpxD genes altered outer membrane (OM) permeability, antimicrobial peptide, and antibiotic susceptibility, whereas only the lpxD1-null mutant was attenuated in mice and subsequently exhibited protection against a lethal WT challenge. Additionally, growth-temperature analysis revealed transcriptional control of the lpxD genes and posttranslational control of the LpxD1 and LpxD2 enzymatic activities. These results suggest a direct mechanism for LPS/lipid A-level modifications resulting in alterations of membrane fluidity, as well as integrity and may represent a general paradigm for bacterial membrane adaptation and virulence-state adaptation.

PMID:
22586119
[PubMed - indexed for MEDLINE]
PMCID:
PMC3365160
Free PMC Article
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