title: The Neisseria meningitidis capsule 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università degli Studi del Salento, Via Monteroni, 73100 Lecce, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Spinosa
authors.forename: Cinzia
authors.initials: C
authors.lastname: Progida
authors.forename: Adelfia
authors.initials: A
authors.lastname: Talà
authors.forename: Laura
authors.initials: L
authors.lastname: Cogli
authors.forename: Pietro
authors.initials: P
authors.lastname: Alifano
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bucci
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D038541:Neisseria meningitidis, Serogroup B / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D020298:U937 Cells / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins