Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

Abstract

Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria.

Modulation ofCaenorhabditis elegansimmune response and modification ofShigellaendotoxin upon interaction

“…The present study concludes that LPS plays a key role in protecting the pathogen from the host immune system as reported in the recent studies . Hence, LPS appeared to have a major role in Shigella ‐mediated pathogenesis and interact with a host defense environment by employing distinct modifications in its content.…”

Global gene expression in Escherichia coli, isolated from the diseased ocular surface of the human eye with a potential to form biofilm

“…cyc A that encodes for glycine, serine and alanine transport is predicted to genetically interact with gene mdt M and is 47-fold down regulated in biofilm forming E. coli cells. cyc A mutant strains of E. coli are known to exhibit significant resistance for d -cycloserine [59]. Thus down regulation of gene cyc A in biofilm forming E. coli cells significantly contributes to antibiotic tolerance.…”

Impact of Actinobacillus pleuropneumoniae biofilm mode of growth on the lipid A structures and stimulation of immune cells

“…47,48,51 Recently, Chalabaev and colleagues described an interesting biofilm associated-phenotype linked to lipid A structure. 47 They found that among several Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa, lipid A can undergo palmitoylation, and these changes were found to be more abundant in biofilm than in planktonic cells.…”

“…47,48,51 Recently, Chalabaev and colleagues described an interesting biofilm associated-phenotype linked to lipid A structure. 47 They found that among several Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa, lipid A can undergo palmitoylation, and these changes were found to be more abundant in biofilm than in planktonic cells. 47 Lipid A structural modifications, including addition of arabinose and palmitate were also observed in P. aeruginosa strains isolated from patients with cystic fibrosis, a chronic lung infection wherein biofilms have a preponderant role.…”