Identification of Genes Involved in Neisseria meningitidis Colonization

Abstract

Neisseria meningitidis is a worldwide cause of meningitis and septicemia leading at least to 50,000 deaths every year. Nevertheless, N. meningitidis is also a commensal bacterium that asymptomatically colonizes the epithelial cells of the nasopharynx of 10 to 30% of healthy individuals. Occasionally, N. meningitidis crosses the nasopharyngeal barrier and enters the bloodstream. During bacteremia, N. meningitidis may adhere to endothelial cells of brain vessels and invade meninges. To identify the genes required for meningococcal host colonization, we screened a signature-tagged transposon mutagenesis library using an innovative in vitro colonization model in order to identify mutants displaying decreased capacity to colonize human epithelial cells. Approximately 1,600 defined insertion mutants of invasive serogroup C strain NEM8013 were screened. Candidate mutants were tested individually for quantification of bacterial biomass with confocal microscope and COMSTAT software. Five mutants were demonstrated to exhibit significantly decreased colonization ability. The identified genes, including narP and estD, appeared to be involved in adaptation to hypoxic conditions and stress resistance. Interestingly, the genes fadD1, nnrS, and NMV_2034 (encoding a putative thioredoxin), prior to this study, had not been shown to be involved in colonization. Therefore, we provide here insights into the meningococcal functions necessary for the bacterium to adapt to growth on host cells.

Sinorhizobium meliloti Controls Nitric Oxide–Mediated Post-Translational Modification of a Medicago truncatula Nodule Protein

“…be part of the arsenal defense of Vibrio cholerae and Rhodobacter sphaeroides 2.4.1 against the toxic effect of NO (Arai et al 2013;Stern et al 2012). In addition, gene disruption experiments showed that NnrS is important in V. cholerae and Neisseria meningitidis for colonization of intestines in the presence of NO, suggesting a role for NnrS in the defense against NO (Jamet et al 2013;Stern et al 2012Stern et al , 2013.…”

Neisserial Molecular Adaptations to the Nasopharyngeal Niche

“…Transcriptomic and proteomic analyses of gonococcal biofilms have revealed a profound shift in bacterial metabolism to supporting anaerobic growth, and there appears to be significant overlap between genes regulated in response to the formation of biofilms, and genes regulated in response to redox-related stresses (Falsetta et al, 2011;Phillips et al, 2012). These findings have been mirrored in the meningococcus (O'Dwyer, Li, Langford, & Kroll, 2009;van Alen et al, 2010), in which targeted deletion of genes involved in adaptation to hypoxic conditions results in impaired biofilm formation on epithelial cells ( Jamet, Euphrasie, Martin, & Nassif, 2013). However, it has recently been hypothesised that the meningococcus is actually mid-evolution, on its way towards a lifestyle as an obligate aerobe (Moir, 2011).…”

Role of Sinorhizobium meliloti and Escherichia coli Long-Chain Acyl-CoA Synthetase FadD in Long-Term Survival

“…However, this enzyme activity also affects a number of different phenotypes. Several studies suggest a role of long-chain fatty acyl-CoA synthetase in pathogenesis since the inactivation of fadD affects virulence or colonization in Pseudomonas aeruginosa [13], Salmonella enterica, serovar Typhimurium [42], and Neisseria meningitidis [43]. The expression of fadD is involved in antibiotic production in Streptomyces coelicolor [44].…”

“…The capacity of fatty acid utilization from the extracellular environment has been described for many Gram-negative as well as for Gram-positive bacteria [43,47] and for yeast [45,48]. It is likely that all microorganisms, pathogenic or environmental, with the capacity to degrade fatty acids benefit from the utilization of exogenous as well as endogenous fatty acids.…”