Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2018

Genomic and transcriptomic analysis of nontypeable Haemophilus influenzae from paediatric chronic lung disease patients (#210)

Ammar Aziz 1 , Derek S. Sarovich 1 2 , Elizabeth Nosworthy 1 , Jemima Beissbarth 1 , Anne Chang 1 , Heidi Smith-Vaughan 1 , Erin P. Price 1 2 , Tegan M. Harris 1
  1. Menzies School of Health Research, Tiwi, NT, Australia
  2. Faculty of Science, Health, Engineering and the Environment, University of the Sunshine Coast, Sunshine Coast, QLD, Australia

Non-typeable Haemophilus influenzae (NTHi) is a commensal bacterium of the upper respiratory tract of healthy children. On occasion, NTHi can infect the lower airways, driving early-stage chronic lung disease. The molecular basis underpinning NTHi transition to a pathogenic lifestyle is poorly understood. Here, we performed comparative genomic and transcriptomic analyses of 12 paired isogenic NTHi strains isolated from the nasopharynx (NP) and bronchoalveolar lavage (BAL) of 11 children with bronchiectasis or chronic suppurative lung disease. Our objective was to identify convergent molecular signatures associated with lung adaptation. Genomic analyses identified five identical NP and BAL pairs, with the remaining seven pairs differed by no more than two mutations. Genetic mutations detected were predominantly deleterious indels. Phylogenomic analysis demonstrated that isolates were sampled from a diverse genetic background, with no clustering between patient isolates (excluding patient 60373). Transcriptomic analyses detected between zero and 58 differentially expressed (DE) genes. DE genes were associated with virulence, immune evasion, epithelial cell adhesion and biofilm formation. Comparison of NP and BAL transcriptomes failed to identify signatures of convergence. However, functional enrichment analysis of within-patient DE genes revealed that BAL isolates were significantly underrepresented in genes involved in translation, ribosomal structure and biogenesis pathways, and significantly over-represented in cell motility, secretion, and carbohydrate transport/metabolism. This observed trend amongst NTHi strains provide clues that pathogen factors play a role in airway adaptation. Our results provide an important first glimpse into the molecular adaptation of NTHi to paediatric airways. Understanding these pathoadaptative mechanisms is essential for devising targeted treatments aimed at minimising exacerbation severity, and ultimately, preventing NTHi lung infections and subsequent chronic lung disease.