Capsule Polysaccharide Mediates Bacterial Resistance to Antimicrobial Peptides

Abstract

The innate immune system plays a critical role in the defense of areas exposed to microorganisms. There is an increasing body of evidence indicating that antimicrobial peptides and proteins (APs) are one of the most important weapons of this system and that they make up the protective front for the respiratory tract. On the other hand, it is known that pathogenic organisms have developed countermeasures to resist these agents such as reducing the net negative charge of the bacterial membranes. Here we report the characterization of a novel mechanism of resistance to APs that is dependent on the bacterial capsule polysaccharide (CPS). Klebsiella pneumoniae CPS mutant was more sensitive than the wild type to human neutrophil defensin 1, ␤-defensin 1, lactoferrin, protamine sulfate, and polymyxin B. K. pneumoniae lipopolysaccharide O antigen did not play an important role in AP resistance, and CPS was the only factor conferring protection against polymyxin B in strains lacking O antigen. In addition, we found a significant correlation between the amount of CPS expressed by a given strain and the resistance to polymyxin B. We also showed that K. pneumoniae CPS mutant bound more polymyxin B than the wild-type strain with a concomitant increased in the self-promoted pathway. Taken together, our results suggest that CPS protects bacteria by limiting the interaction of APs with the surface. Finally, we report that K. pneumoniae increased the amount of CPS and upregulated cps transcription when grown in the presence of polymyxin B and lactoferrin.

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

“…This raises the possibility that the markedly reduced carbohydrate attachments on the envelope proteins of this strain (61) allow greater interaction with the defensins. Note that the carbohydrate capsule of some bacteria contributes to resistance against defensins (62). Although HNPs and defensins have been found to have lectin activity (63), our findings suggest that this type of activity is unlikely to account for binding to IAV.…”

Regulation of bacterial virulence gene expression by cell envelope stress responses

“…110 Nevertheless, polysaccharide capsules are widely conserved and in some cases they are virulence factors associated with resistance to phagocytosis and to host antimicrobial molecules. [111][112][113] Furthermore, the Rcs response has been implicated in regulating production of E. coli group I capsules, which are important virulence determinants. In some E. coli strains the production of group I capsule was induced by overexpression of rcsB.…”

Antimicrobial Peptide Resistance Mechanisms of Human Bacterial Pathogens

“…It will be interesting in future studies to explore a potential role of acidic sugar capsules in AMP trapping as an additional selective advantage. Such a correlation has recently been suggested for the pathogen Klebsiella pneumoniae, as mutants lacking capsular polysaccharide were demonstrated to be more susceptible to a variety of cationic AMPs including human α-and β-defensins (Campos et al, 2004).…”