Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2021

In vitro Probiotic Potential of Haemophilin-producing Strains of Haemophilus haemolyticus (#19)

Brianna Atto 1 , Dale Kunde 1 , David A Gell 2 , Steve Tristram 1
  1. School of Health Sciences, University of Tasmania , Launceston, TAS, Australia
  2. School of Medicine, University of Tasmania , Hobart, TAS, Australia

Nontypeable Haemophilus influenzae (NTHi) is a significant respiratory tract pathogen responsible for a variety of infections that collectively pose a substantial global health burden. The rapidly evolving antibiotic resistance profile of NTHi isolates and the absence of an effective vaccination strategy, emphasizes the need for alternative therapeutic approaches. The course of NTHi infection is dictated by successful colonisation and invasion of nasopharyngeal epithelial cells and approaches that disrupt these interactions may therefore have a significant impact on the ability of NTHi to cause infection. An important determinant of interactions with host cells and survival within the respiratory tract is the ability of NTHi to scavenge host-derived sources of the essential growth factor, haem. We previously characterised novel strains of Haemophilus haemolyticus (Hh) capable of producing haemophilin (Hpl), a haem-binding protein that restricts NTHi growth by limiting its access to haem1. Here, we assess the in vitro inhibitory activity of Hh strains with varying capacities to produce Hpl and postulate their potential utility as a probiotic in the respiratory tract. During short-term and extended broth co-culture, Hpl-producing strains of Hh outcompeted NTHi. Similarly, in tissue culture models of nasopharyngeal and lung epithelia, Hh strains with high levels of hpl expression protected cell monolayers against adhesion and invasion by NTHi. In both models, this NTHi-inhibitory activity correlated with levels of hpl expression and Hpl protein quantified from competition media. The absence of NTHi-inhibitory activity in a hpl knockout or native non-producing strains confirmed that the inhibitory phenotype was mediated by the ability to produce Hpl. Collectively, these observations demonstrate that Hpl-producing Hh may be a promising respiratory probiotic candidate for the prevention of NTHi infections by inhibiting requisite nasopharyngeal colonisation.

 

  1. Latham RD, et al. 2020. Molecular microbiology 113:381-398 (doi: 10.1111/mmi.14426).