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Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2.

ABSTRACT: Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171-240 and 91-99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains.

SUBMITTER: Abouseada NM

PROVIDER: S-EPMC3457995 | biostudies-literature |

REPOSITORIES: biostudies-literature

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PorA variable regions of Neisseria meningitidis.

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Changes in Invasive <i>Neisseria meningitidis</i> and <i>Haemophilus influenzae</i> Infections in France during the COVID-19 Pandemic.

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| S-EPMC9147110 | biostudies-literature

Neisseria meningitidis porA, fetA and fHbp gene distribution in Western Australia 2000 to 2011.

Project description:BackgroundPorA, fetA and fHbp are three antigen encoding genes useful for meningococcal typing and FHbp is an important component of meningococcal B vaccines.MethodsWe performed sequence analysis of meningococcal porA, fetA and fHbp genes on 128 isolates from Western Australia, relating results to age, gender, race and geographic region.ResultsWe found predominantly PorA subtypes P1.22,14-16 (n?=?23) and P1.7-2,4 (n?=?19); FetA subtypes F1-5 (n?=?41), F3-6 (n?=?11), F5-1 (n?=?10), F5-2 (n?=?9), F5-5 (n?=?8), F3-3 (n?=?8); and FHbp variant groups 1 (n?=?65) and 2 (n?=?44). PorA P1.22,14-16 and FHbp variant group 2 were associated with younger age and aboriginality.ConclusionsFHbp modular groups of the bivalent recombinant FHbp vaccine and the multicomponent 4CMenB vaccine make up 8.3% and 47.7% respectively of the examined serogroup B isolates from 2000-2011, however to estimate vaccine efficacy requires an account of all vaccine antigens and their levels of expression.

| S-EPMC4266217 | biostudies-literature

Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR.

Project description:A single-tube 5' nuclease multiplex PCR assay was developed on the ABI 7700 Sequence Detection System (TaqMan) for the detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae from clinical samples of cerebrospinal fluid (CSF), plasma, serum, and whole blood. Capsular transport (ctrA), capsulation (bexA), and pneumolysin (ply) gene targets specific for N. meningitidis, H. influenzae, and S. pneumoniae, respectively, were selected. Using sequence-specific fluorescent-dye-labeled probes and continuous real-time monitoring, accumulation of amplified product was measured. Sensitivity was assessed using clinical samples (CSF, serum, plasma, and whole blood) from culture-confirmed cases for the three organisms. The respective sensitivities (as percentages) for N. meningitidis, H. influenzae, and S. pneumoniae were 88.4, 100, and 91.8. The primer sets were 100% specific for the selected culture isolates. The ctrA primers amplified meningococcal serogroups A, B, C, 29E, W135, X, Y, and Z; the ply primers amplified pneumococcal serotypes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10A, 11A, 12, 14, 15B, 17F, 18C, 19, 20, 22, 23, 24, 31, and 33; and the bexA primers amplified H. influenzae types b and c. Coamplification of two target genes without a loss of sensitivity was demonstrated. The multiplex assay was then used to test a large number (n = 4,113) of culture-negative samples for the three pathogens. Cases of meningococcal, H. influenzae, and pneumococcal disease that had not previously been confirmed by culture were identified with this assay. The ctrA primer set used in the multiplex PCR was found to be more sensitive (P < 0.0001) than the ctrA primers that had been used for meningococcal PCR testing at that time.

| S-EPMC87969 | biostudies-literature

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