Nancy ElChaar

Conference 2024 Live Talk

Talk Title

Identifying anti-pneumococcal molecules in the upper respiratory tract microbiome

Authors and Affiliations

ElChaar, Nancy1, Bowdish, Dawn M.E.1,3, Surette, Michael G1,2.

1. McMaster University, Department of Medicine, Hamilton, ON, Canada
2. McMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, ON, Canada
3. Firestone Institute for Respiratory Health, St. Joseph’s Healthcare Hamilton, Canada, McMaster University

Abstract

Background

Pneumonia is a leading cause of death in older adults and can significantly decrease quality of life by exacerbating other diseases. Bacterial pneumonia begins with the colonization of pathogens in the upper respiratory tract (URT), most commonly Streptococcus pneumoniae, before progressing to the lower airways. The microbiota of the respiratory tract acts as gatekeepers, providing a first line of defence against infection. Pathogens compete with the resident microbiota for nutrients and space, and some commensal bacteria have been shown to produce antimicrobial compounds. These protective microbes can be lost with age, increasing susceptibly to infection. We aim to identify the specific compounds that commensals produce to directly suppress the growth and colonization of pathogens in the URT.

Methods

This project investigates commensal URT bacteria that directly inhibit S. pneumoniae. We have generated a diverse library of over 2,000 microbial strains cultured from the middle turbinate nasal cavity from 21 healthy individuals. These isolates were screened for antimicrobial activity against S. pneumoniae using zone of inhibition assays. Activity guided purification of selected strains, including reverse phase chromatography and mass spectrometry, was used to identify bioactive molecules. This biochemical approach is complemented by comparative genomic analysis. Secondary metabolite pathways and bacteriocin gene clusters are being identified using specialized programs (e.g., antiSMASH, DeepBGC, BAGEL4).

Results

From the bioassays, 46 isolates from our collection (representing 7 genera and 13 species) were shown to have anti-pneumococcal activity. We have observed the inhibitory activity to be strain- rather than species-specific. The active isolates include several strains of Corynebacterium, which have previously been described to outcompete S. pneumoniae, and therefore, are of particular interest. The Corynebacterium inhibitory activities are distinct from those previously reported. We have identified metabolites using our biochemical approach, and we are currently investigating the genome sequences of these isolates to predict potential pathways and biochemical mechanisms.

Conclusions

The findings of this project will identify mechanisms of competition in the URT, as well as determine URT microbiota (and their products) with the potential to produce novel, narrow-spectrum, antibiotics to mitigate the risk of URT infections particularly in an aging population.