Nontypable Haemophilus influenzae Displays a Prevalent Surface Structure Molecular Pattern in Clinical Isolates

Martí-Lliteras, Pau; López−Gómez, Antonio; Mauro, Silvia; Hood, Derek W.; Viadas, Cristina; Calatayud, Laura; Morey, Pau; Servin, Alain L.; Liñares, Josefina; Oliver, Antonio; Bengoechea, José A.; Garmendia, Junkal

doi:10.1371/journal.pone.0021133

Cited by 21 publications

(25 citation statements)

References 60 publications

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“…A good association between the presence of the necessary genes to sialylate LOS (nanH, siaB or neuA and lsgB) and serum resistance was observed (kappa5 0.788), while the association with phagocytosis resistance was weaker (kappa50.462). These results give strength to the hypothesis that LOS sialylation could confer an increased resistance to the bactericidal effect of sera and could be involved in modulating H. parasuis resistance to complement, as has been observed for H. influenzae (Hood et al, 1999;Martí-Lliteras et al, 2011;Nakamura et al, 2011). …”

Section: Amplification Sequencing and Heterologous Expression Of Nanhsupporting

confidence: 75%

Distribution of genes involved in sialic acid utilization in strains of Haemophilus parasuis

et al. 2012

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Haemophilus parasuis is a porcine respiratory pathogen, well known as the aetiological agent of Glä sser's disease. H. parasuis comprises strains of different virulence, but the virulence factors of this bacterium are not well defined. A neuraminidase activity has been previously detected in H. parasuis, but the role of sialylation in the virulence of this bacterium has not been studied. To explore the relationship between sialic acid (Neu5Ac) and virulence, we assessed the distribution of genes involved in sialic acid metabolism in 21 H. parasuis strains from different clinical origins (including nasal and systemic isolates). The neuraminidase gene nanH, together with CMPNeu5Ac synthetase and sialyltransferase genes neuA, siaB and lsgB, were included in the study. Neuraminidase activity was found to be common in H. parasuis isolates, and the nanH gene from 12 isolates was expressed in Escherichia coli and further characterized. Sequence analysis showed that the NanH predicted protein contained the motifs characteristic of the catalytic site of sialidases. While an association between the presence of nanH and the different origins of the strains was not detected, the lsgB gene was predominantly present in the systemic isolates, and was not amplified from any of the nasal isolates tested. Analysis of the lipooligosaccharide (LOS) from reference strains Nagasaki (virulent, lsgB + ) and SW114 (non-virulent, lsgB " ) showed the presence of sialic acid in the LOS from the Nagasaki strain, supporting the role of sialylation in the virulence of this bacterial pathogen. Further studies are needed to clarify the role of sialic acid in the pathogenicity of H. parasuis.

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Section: Amplification Sequencing and Heterologous Expression Of Nanhsupporting

confidence: 75%

Distribution of genes involved in sialic acid utilization in strains of Haemophilus parasuis

et al. 2012

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“…S1 in the supplemental material), which likely accounts for the difference in function. Of note, in a survey of the serum resistance of 18 clinical NTHi isolates, MartiLliteras et al identified a strain with a predicted truncation of P5 that exhibited a moderate level of serum resistance albeit a level lower than that of 16 of the 17 other strains tested (71). Therefore, it is possible that some clinical isolates may possess an alternative fH-binding mechanism contributing resistance analogous to that of Rd, and it will be of interest to evaluate this possibility with isogenic mutants.…”

Section: Discussionmentioning

confidence: 99%

Outer Membrane Protein P5 Is Required for Resistance of Nontypeable Haemophilus influenzae to Both the Classical and Alternative Complement Pathways

2014

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The complement system is an important first line of defense against the human pathogen Haemophilus influenzae. To survive and propagate in vivo, H. influenzae has evolved mechanisms for subverting this host defense, most of which have been shown to involve outer surface structures, including lipooligosaccharide glycans and outer surface proteins. Bacterial defense against complement acts at multiple steps in the pathway by mechanisms that are not fully understood. Here we identify outer membrane protein P5 as an essential factor in serum resistance of both H. influenzae strain Rd and nontypeable H. influenzae (NTHi) clinical isolate NT127. P5 was essential for resistance of Rd and NT127 to complement in pooled human serum. Further investigation determined that P5 expression decreased cell surface binding of IgM, a potent activator of the classical pathway of complement, to both Rd and NT127. Additionally, P5 expression was required for NT127 to bind factor H (fH), an important inhibitor of alternative pathway (AP) activation. Collectively, the results obtained in this work highlight the ability of H. influenzae to utilize a single protein to perform multiple protective functions for evading host immunity.

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“…1A). The frequency of lic2C distribution among strains is variable, depending on the strain set (8,59). We generated a series of mutants that express serial LOS truncations and then assessed their effect on a number of traits relating to bacterial interplay with the host.…”

Section: Discussionmentioning

confidence: 99%

Relative Contributions of Lipooligosaccharide Inner and Outer Core Modifications to Nontypeable Haemophilus influenzae Pathogenesis

et al. 2013

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e Nontypeable Haemophilus influenzae (NTHi) is a frequent commensal of the human nasopharynx that causes opportunistic infection in immunocompromised individuals. Existing evidence associates lipooligosaccharide (LOS) with disease, but the specific and relative contributions of NTHi LOS modifications to virulence properties of the bacterium have not been comprehensively addressed. Using NTHi strain 375, an isolate for which the detailed LOS structure has been determined, we compared systematically a set of isogenic mutant strains expressing sequentially truncated LOS. The relative contributions of 2-keto-3-deoxyoctulosonic acid, the triheptose inner core, oligosaccharide extensions on heptoses I and III, phosphorylcholine, digalactose, and sialic acid to NTHi resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation, cultured human respiratory epithelial infection, and murine pulmonary infection were assessed. We show that opsX, lgtF, lpsA, lic1, and lic2A contribute to bacterial resistance to AMP; lic1 is related to NTHi self-aggregation; lgtF, lic1, and siaB are involved in biofilm growth; opsX and lgtF participate in epithelial infection; and opsX, lgtF, and lpsA contribute to lung infection. Depending on the phenotype, the involvement of these LOS modifications occurs at different extents, independently or having an additive effect in combination. We discuss the relative contribution of LOS epitopes to NTHi virulence and frame a range of pathogenic traits in the context of infection.

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Nontypable Haemophilus influenzae Displays a Prevalent Surface Structure Molecular Pattern in Clinical Isolates

Cited by 21 publications

References 60 publications

Distribution of genes involved in sialic acid utilization in strains of Haemophilus parasuis

Distribution of genes involved in sialic acid utilization in strains of Haemophilus parasuis

Outer Membrane Protein P5 Is Required for Resistance of Nontypeable Haemophilus influenzae to Both the Classical and Alternative Complement Pathways

Relative Contributions of Lipooligosaccharide Inner and Outer Core Modifications to Nontypeable Haemophilus influenzae Pathogenesis

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