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Invasion by Neisseria meningitidis varies widely between clones and among nasopharyngeal mucosae derived from adult human hosts

Division of Genomic Medicine, F Floor, Sheffield University Medical School, Beech Hill Road, Sheffield S10 2RX, UK¹
School of Public Health, University of Nottingham, UK²
Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, UK³

Author for correspondence: Robert C. Read. Tel: +44 114 272 4072. Fax: +44 114 273 9926. e-mail: r.c.read{at}shef.ac.uk

Colonization of the human nasopharynx is a feature of some species of Neisseria, and is a prerequisite of invasive meningococcal disease. The likelihood of colonization by Neisseria meningitidis varies widely between humans, and very few develop invasive disease. Explants of nasal mucosa derived from adult patients with non-allergic nasal obstruction were infected experimentally with Neisseria spp. At intervals over 18 h incubation, washed explants were homogenized, and viable bacteria were counted. To estimate bacterial invasion of mucosa, explants were exposed to 0·25% sodium taurocholate for 30 s prior to homogenization. N. meningitidis was recovered from the mucosa and the organism invaded and replicated within the tissue, in contrast to N. lactamica and N. animalis (n=9, P<0·008). N. meningitidis isolates of clones ET-5, ET-37 and lineage III were recovered from and invaded tissue, but strains of clones A4, A:subgroup I, A:subgroup III and A:subgroup IV-1 did not invade (n=6). To measure host variation, survival of N. meningitidis within nasal mucosa of 40 different human donors was measured. Intra-class correlation of replicates was 0·97, but the coefficient of variation of recovered viable counts was 1335% after 4 h and 77% after 18 h incubation. It is concluded that the distinctive colonization and disease potential of Neisseria spp. may be partly a consequence of their ability to invade and survive within human nasopharyngeal mucosa, but that this is influenced greatly by genetic or environmental factors operating on the host mucosa. This is consistent with the unpredictable epidemiology of meningococcal disease.

Keywords: pathogenesis, colonization, Neisseria lactamica, Neisseria animalis

Abbreviations: MBC, mean bactericidal concentration

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