TheNeisseria meningitidisCapsule Is Important for Intracellular Survival in Human Cells

Abstract

While much data exist in the literature about how Neisseria meningitidis adheres to and invades human cells, its behavior inside the host cell is largely unknown. One of the essential meningococcal attributes for pathogenesis is the polysaccharide capsule, which has been shown to be important for bacterial survival in extracellular fluids. To investigate the role of the meningococcal capsule in intracellular survival, we used B1940, a serogroup B strain, and its isogenic derivatives, which lack either the capsule or both the capsule and the lipooligosaccharide outer core, to infect human phagocytic and nonphagocytic cells and monitor invasion and intracellular growth. Our data indicate that the capsule, which negatively affects bacterial adhesion and, consequently, entry, is, in contrast, fundamental for the intracellular survival of this microorganism. The results of in vitro assays suggest that an increased resistance to cationic antimicrobial peptides (CAMPs), important components of the host innate defense system against microbial infections, is a possible mechanism by which the capsule protects the meningococci in the intracellular environment. Indeed, unencapsulated bacteria were more susceptible than encapsulated bacteria to defensins, cathelicidins, protegrins, and polymyxin B, which has long been used as a model compound to define the mechanism of action of CAMPs. We also demonstrate that both the capsular genes (siaD and lipA) and those encoding an efflux pump involved in resistance to CAMPs (mtrCDE) were up-regulated during the intracellular phase of the infectious cycle.

Capsule polysaccharide is a bacterial decoy for antimicrobial peptides

“…We showed that mutants of Klebsiella pneumoniae lacking CPS were more sensitive to APs than wild-type strains (Campos et al, 2004). A higher susceptibility of a Neisseria meningitidis CPS mutant to APs was also observed (Spinosa et al, 2007). Mechanistically, it has been speculated that CPS would act as a protective shield on the bacterial surface (Campos et al, 2004;Spinosa et al, 2007).…”

“…We and others have suggested that surface-bound CPS may act as a protective shield on the bacterial surface against APs (Campos et al, 2004;Spinosa et al, 2007). In this Table 3.…”

“…A higher susceptibility of a Neisseria meningitidis CPS mutant to APs was also observed (Spinosa et al, 2007). Mechanistically, it has been speculated that CPS would act as a protective shield on the bacterial surface (Campos et al, 2004;Spinosa et al, 2007). In contrast, a Campylobacter jejuni mutant lacking CPS was as resistant as the wild-type to APs, whereas capsulated Streptococcus pneumoniae from serotypes 1, 2 and 4 were even more sensitive to APs than the isogenic CPS mutants (Beiter et al, 2008;Zilbauer et al, 2005).…”

Endotoxin, Capsule, and Bacterial Attachment Contribute to Neisseria meningitidis Resistance to the Human Antimicrobial Peptide LL-37

“…In particular, two capsule genes, NMB0068 (siaC) and NMB0067 (siaD), were found to have been upregulated 2.57-fold and 2.20-fold, respectively, after 30 min of LL-37 treatment, while lipA (encoding a capsule polysaccharide modification protein) was upregulated 1.3-fold after 30 min but not after 60 min. Spinosa et al (26) also found that lipA was upregulated 1.6-fold in response to treatment with sublethal concentrations of LL-37. We verified the altered gene transcription data by performing real-time RT-PCR using bacteria treated with sublethal concentrations of LL-37.…”

“…The neisserial capsule protects bacteria from LL-37. It has previously been shown that capsule polysaccharides from gram-negative bacteria contribute to resistance to AMP (3,26). In particular, Spinosa et al (26) demonstrated that the capsule plays a key defensive role, protecting intracellular serogroup B N. meningitidis from various AMPs.…”