Nontypable Haemophilus influenzae surface structure molecular pattern and associated virulence phenotypes in unrelated and serial clinical isolates

Abstract

[Aim] Non-typable Haemophilus influenzae (NTHi) causes acute respiratory infections, is associated with the progression of chronic respiratory diseases, and responsible for a high proportion of exacerbations. We analysed population dynamics, diversity of bacterial surface-related gene patterns and associated sequences, and virulence-related phenotypes in (i) NTHi strains from respiratory and non-respiratory samples isolated from unrelated patients, and (ii) NTHi serial isolates from COPD exacerbations.

[Methods] (i) 111 NTHi isolates from unrelated patients were used to analyse nine genes encoding surface molecules. PCR- and sequencing-based genetic profiles were associated to bacterial resistance to serum mediated killing and epithelial adhesion. (ii) 54 serial NTHi isolates from 20 COPD patients isolated in exacerbation were used to establish genotypic dynamics, bacterial surface molecules conservation, and association to bacterial resistance to antimicrobial peptides and epithelial adhesion.

[Results] (i) 94.6% of unrelated NTHi isolates presented one prevalent molecular pattern. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells. (ii) Serial NTHi strains from COPD exacerbations could have identical genotypes, different genotypes, or alternation of isogenic and nonisogenic isolates. Identical strains conserved molecular pattern and ompP5 and oapA gene sequences, otherwise variable among different isolates, but displayed variation in the number of simple sequence repeats in lic1A and lic2B.

[Conclusions] The prevalence of particular surface related molecular features can be advantageous for NTHi. The selection of bacterial clones endowed with those features may be modulated by the host.