Helicobacter pylori Resists the Antimicrobial Activity of Calprotectin via Lipid A Modification and Associated Biofilm Formation

ABSTRACT Helicobacter pylori is one of several pathogens that persist within the host despite a robust immune response.H. py-lori elicits a proinflammatory response from host epithelia, resulting in the recruitment of immune cells which manifests as gas-tritis. Relatively little is known about howH. pylori survives antimicrobials, including calprotectin (CP), which is present during the inflammatory response. The data presented here suggest that one wayH. pylori survives the nutrient sequestration by CP is through alteration of its outer membrane. CP-treatedH. pylori demonstrates increased bacterial fitness in response to further coculture with CP. Moreover, CP-treatedH. pylori cultures form biofilms and demonstrate decreased cell surface hydrophobic-ity. In response to CP, theH. pylori Lpx lipid A biosynthetic enzymes are not fully functional. The lipid Amolecules observed in H. pylori cultures treated with CP indicate that the LpxF, LpxL, and LpxR enzyme functions are perturbed. Transcriptional anal-ysis of lpxF, lpxL, and lpxR indicates that metal restriction by CP does not control this pathway through transcriptional regula-tion. Analyses ofH. pylori lpx mutants reveal that loss of LpxF and LpxL results in increased fitness, similar to what is observed in the presence of CP; moreover, these mutants have significantly increased biofilm formation and reduced cell surface hydro