Humoral Immunity against Capsule Polysaccharide Protects the Host from magA ⁺ Klebsiella pneumoniae -Induced Lethal Disease by Evading Toll-Like Receptor 4 Signaling

Abstract

Klebsiella pneumoniae magA (for mucoviscosity-associated gene A) is linked to the pathogenesis of primary pyogenic liver abscess, but the underlying mechanism by which magA increases pathogenicity is not well elucidated. In this study, we investigated the role of the capsular polysaccharides (CPS) in the pathogenesis of magA ؉ K. pneumoniae by comparing host immunity to magA ؉ K. pneumoniae and a ⌬magA mutant. We found that Toll-like receptor 4 recognition by magA ؉ K. pneumoniae was hampered by the mucoviscosity of the magA ؉ K. pneumoniae CPS. Interestingly, monoclonal antibodies (MAbs) against magA ؉ K. pneumoniae CPS recognized all of the K1 strains tested but not the ⌬magA and non-K1 strains. Moreover, the anti-CPS MAbs protected mice from magA ؉ K. pneumoniae-induced liver abscess formation and lethality. This indicates that the K1 epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from K1 strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future.

Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital

“…All 16 strains analyzed here possessed the mrk and fim operons, coding for fimbrial genes (11,12), and the ent operon, coding for enterobactin (14), consistent with previous results showing that these genes are highly conserved in K. pneumoniae (19,30). None of the isolates demonstrated rmpA and wzy-K1 (magA) genes, which are hypermucoviscosity-associated genes (16,17,19).…”

“…Capsular types, particularly K1 and K2, and hypermucoviscosity, favored by the positive regulator genes rmpA and rmpA2, are also important for K. pneumoniae virulence. Capsule production increases resistance to phagocytosis and other immune response components (16,17). For detailed descriptions of these and other potential virulence factors of K. pneumoniae, see references 18 and 19. Most of the KPC-producing K. pneumoniae strains isolated worldwide have been attributed to clonal group 258 (CG258) (19,20).…”

Roles of Capsule and Lipopolysaccharide O Antigen in Interactions of Human Monocyte-Derived Dendritic Cells and Klebsiella pneumoniae

“…Elevated levels of TLR4 on DCs and epithelial cells, acting in a coordinated manner upon K. pneumoniae infection, could thus trigger a powerful immune response. This hypothesis is strengthened by the recent data of Wu et al, who reported that TLR4 is involved in host recognition of K. pneumoniae in macrophage cell lines (46). In their study, the wildtype K. pneumoniae induced downregulation of DC-SIGN.…”

RmpA Regulation of Capsular Polysaccharide Biosynthesis inKlebsiella pneumoniaeCG43

“…In addition, it is also involved in virulence properties (46,50), acid stress response (13), osmotic shock (17), and chemotaxis (10). In the present study, a negative role of Fur in CPS biosynthesis that is achieved by the reduction of the RmpA expression is re- ported for the first time.…”