Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2018

Sugar & Spice – insights into the ‘diet’ of Haemophilus influenzae in the host (#129)

Ulrike Kappler 1 , Jennifer Hosmer 1 , Marufa Nasreen 1 , Anna Henningham 2 , Rabeb Dhouib 1 , Horst Schirra 3 , Emmanuelle Fantino 2 , Peter Sly 2 , Alastair McEwan 1
  1. School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  2. Child Health Research Centre, The University of Queensland, South Brisbane, Qld, Australia
  3. Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, Australia

Haemophilus influenzae is a host adapted human pathogen involved in acute and chronic respiratory diseases. The severity of disease caused by the prevalent non-typeable strains (NTHi) as well as antibiotic resistance is increasing, making the identification of alternative targets for undermining NTHi fitness essential. One possible avenue to achieve this is to target genes involved in central NTHi metabolism, thus undermining energy generation.  Interestingly, very little is known about the nutritional requirements of H. influenzae and their relevance to in-host survival, and we have investigated this using several non-typeable strains of H. influenzae. Phenotypic microarrays revealed that despite genetic diversity, the carbon source utilization profiles of the NTHi strains is similar. Less than 20 carbohydrates (e.g. ribose) and carboxylic acids (e.g. lactate) were highly used by all strains, and several of these matched known components of airway mucin glycans and host cell metabolic endproducts. Nucleosides and nucleotides were the only major N- and P sources utilized by NTHi strains. All strains showed high tolerance to high pH (up to at least pH 9) and osmolyte stress, being able to tolerate high concentrations of NaCl, KCl, nitrate and nitrite. An interesting observation was that the only systematic deviations from the general profile were associated with two blood isolates suggesting a possible associated with niche adaptation. Analysis of metabolites formed and consumed in single and co-cultures of NTHi with human bronchial cells (16HBE14) and air-liquid interface differentiated epithelia by 1H-NMR revealed that NTHi consumed lactate produced by the host cells as well as glucose present in the medium, with RNAseq analyses revealing that enzymes involved in lactate conversions are highly expressed during host-NTHi co-culture. NTHi nutritional profiles are thus closely adapted to its niche in the host, and appear to be highly conserved between otherwise genetically variable strains.