Antigenic and/or phase variation of PorA protein in non-subtypable Neisseria meningitidis strains isolated in Spain

Alcalá, Belén; Salcedo, Celia; Arreaza, L.; Abad, Raquel; Enriquez, Rocío; Fuente, Laura de la; Uría, María José; Vázquez, Julio A.

doi:10.1099/jmm.0.05517-0

Cited by 24 publications

(16 citation statements)

References 23 publications

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“…Such mispairing would lead to phase-variable expression of msbB by placing the gene out of frame. Phase-variable expression in Neisseria species is more often associated with longer homopolymeric runs of guanine bases, but there is one report of phase variation resulting from a polyadenine tract in the promoter of the porA gene in N. meningitidis (30). Recent studies have also found associations between lipid A phosphorylation, diphosphorylation, and phosphotidyl ethanolamine (PEA) decoration and the potency of TLR4 activation and host inflammatory cytokine production (25,(31)(32)(33).…”

Section: Discussionmentioning

confidence: 95%

Hexa-Acylated Lipid A Is Required for Host Inflammatory Response to Neisseria gonorrhoeae in Experimental Gonorrhea

et al. 2014

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e Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted infection characterized by inflammation of the cervix or urethra. However, a significant subset of patients with N. gonorrhoeae remain asymptomatic, without evidence of localized inflammation. Inflammatory responses to N. gonorrhoeae are generated by host innate immune recognition of N. gonorrhoeae by several innate immune signaling pathways, including lipooligosaccharide (LOS) and other pathogen-derived molecules through activation of innate immune signaling systems, including toll-like receptor 4 (TLR4) and the interleukin-1␤ (IL-1␤) processing complex known as the inflammasome. The lipooligosaccharide of N. gonorrhoeae has a hexa-acylated lipid A. N. gonorrhoeae strains that carry an inactivated msbB (also known as lpxL1) gene produce a penta-acylated lipid A and exhibit reduced biofilm formation, survival in epithelial cells, and induction of epithelial cell inflammatory signaling. We now show that msbB-deficient N. gonorrhoeae induces less inflammatory signaling in human monocytic cell lines and murine macrophages than the parent organism. The penta-acylated LOS exhibits reduced toll-like receptor 4 signaling but does not affect N. gonorrhoeae-mediated activation of the inflammasome. We demonstrate that N. gonorrhoeae msbB is dispensable for initiating and maintaining infection in a murine model of gonorrhea. Interestingly, infection with msbB-deficient N. gonorrhoeae is associated with less localized inflammation. Combined, these data suggest that TLR4-mediated recognition of N. gonorrhoeae LOS plays an important role in the pathogenesis of symptomatic gonorrhea infection and that alterations in lipid A biosynthesis may play a role in determining symptomatic and asymptomatic infections. L ipopolysaccharide (LPS) is an importance virulence factor in Gram-negative bacteria. LPS consists of a complex polysaccharide attached to a core saccharide consisting of 3-deoxy-Dmannooctulosonic acid (keto-deoxyoctulosonate [KDO]) and an acylated diglucosamine moiety known as lipid A. Neisseria species (as well as some other commensal and pathogenic bacteria) make LPS with a truncated polysaccharide structure, which is termed lipooligosaccharide (LOS). LOS is a potent mediator of inflammatory signaling and is known to activate several host innate immune signaling systems, including toll-like receptor 4 (TLR4) through the lipid A molecule, C-lectin receptors (particularly MGL and DC-SIGN) through the oligosaccharide structure, and the caspase-1 activating complex known as the NLRP3-inflammasome through mechanisms yet to be determined (1-4).Lipid A synthesis is largely carried out by a highly conserved set of enzymatic steps that include the acylation of glucosaminebased precursors followed by condensation of these acylated glucosamine structures into the tetra-acylated disaccharide backbone that is the core structure of lipid A. This core is further decorated by the addition of two KDOs (2) and a variety of other additional modifications of the lipidated dis...

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Section: Discussionmentioning

confidence: 95%

Hexa-Acylated Lipid A Is Required for Host Inflammatory Response to Neisseria gonorrhoeae in Experimental Gonorrhea

et al. 2014

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“…Therefore, we have performed an antigenic and genetic characterization of serogroup Y isolates collected at the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, and Costa Rica, which were isolated for over a 7-year period (2000e2006). These analyses included serological assays to determine serogroup/serotype/serosubtype, DNA sequencing and genotyping of the porB and/or porA gene, 9,10 and multilocus sequence typing (MLST). MLST is the preferred format for data collection by the global surveillance for N. meningitidis, PubMLST 3 (http:// www.mlst.net/).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region

Abad¹,

Agudelo²,

Brandileone³

et al. 2009

Journal of Infection

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“…The development of a broadly protective vaccine against group B meningococci (MenB) has been hampered by ineffective MenB capsular polysaccharide vaccines and extensive variability of outer membrane proteins targeted by vesicle-based vaccines (1,11,15,16). We have approached this problem by selecting candidate antigens encoded on the MenB genome that can individually serve as targets for protective antibody responses yet are very distinct from each other (6,13).…”

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confidence: 99%

“…Because of the extensive diversity observed in MenB strains for antigens such as the porins and pili (1,2,16), it is possible that resistance to bactericidal antibodies might occur via selective pressure from vaccination. While it is difficult to model in vitro the cumulative effects of the general use of a vaccine in a large human population over a sustained period, these studies show that within the expected range of appearance of phase variants, a loss of susceptibility to bactericidal antibodies raised by these MenB vaccine combinations was not observed.…”

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confidence: 99%

Investigation on the Effect of Immune Selection on Resistance to Bactericidal Antibodies to Group B Meningococci In Vitro

Santos

Giuliani

Santini

et al. 2009

Clin Vaccine Immunol

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Antigenic and/or phase variation of PorA protein in non-subtypable Neisseria meningitidis strains isolated in Spain

Cited by 24 publications

References 23 publications

Hexa-Acylated Lipid A Is Required for Host Inflammatory Response to Neisseria gonorrhoeae in Experimental Gonorrhea

Hexa-Acylated Lipid A Is Required for Host Inflammatory Response to Neisseria gonorrhoeae in Experimental Gonorrhea

Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region

Investigation on the Effect of Immune Selection on Resistance to Bactericidal Antibodies to Group B Meningococci In Vitro

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