Neisseria meningitides. uusi virulenssifenotyyppi

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Infect Immun. 2012 Apr 16. [Epub ahead of print]

Invasive potential of non-encapsulated disease isolates of Neisseria meningitidis.

Johswich KO, Zhou J, Law DK, St Michael F, McCaw SE, Jamieson FB, Cox AD, Tsang RS, Gray-Owen SD.

Source

Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Abstract

The capsule of Neisseria meningitidis is the major virulence factor that enables these bacteria to overcome host immunity elicited by complement and phagocytes, rendering them capable of surviving in blood. As such, non-encapsulated N. meningitidis isolates are generally considered non-pathogenic. Here, we consider the inherent virulence of two non-encapsulated N. meningitidis isolates obtained from our national surveillance of infected blood cultures in Canada. Capsule deficiency of both strains was confirmed by serology and PCR for ctrA-D and siaA-C genes, as well as serogroups B, C, Y, and W-135 specific siaD genes. In both strains, the capsule synthesis genes are replaced by the capsule null locus, cnl-2. In accordance with a lack of capsule, both strains were fully susceptible to killing by both, human and baby rabbit complement. However, in presence of cytidine-5' monophospho-N-acetylneuraminic acid (CMP-NANA), allowing for LOS sialylation, a significant increase of resistance to complement killing was observed. Mass spectrometry of purified lipooligosaccharide (LOS) did not reveal any uncommon modifications that would explain their invasive phenotype. Finally, in a mouse intraperitoneal challenge model, these non-encapsulated isolates displayed enhanced virulence relative to an isogenic mutant strain of serogroup B strain MC58 lacking capsule (MC58ΔsiaD). Virulence of all non-encapsulated isolates tested was below that of encapsulated serogroup B strains MC58 or B16B6. However, whereas no mortality was observed with MC58ΔsiaD, 5/10 mice succumbed to infection with strain 2275 and 2/11 mice succumbed to strain 2274. Our results suggest the acquisition of a new virulence phenotype by these non-encapsulated strains.

PMID:

22508859

[PubMed - as supplied by publisher]