About MacSphere

MacSphere is McMaster University's Institutional Repository. MacSphere brings together the institution's scholarly works under one umbrella to preserve and provide ongoing open access to them. MacSphere works have been selected and deposited by members of the McMaster community as part of our collective committment to sharing our knowledge with the world.

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Recent Submissions

Identifying Colonization Resistance Activities of the Commensal Upper Respiratory Tract Microbiota
(2026) ElChaar, Nancy; Surette, Michael; Bowdish, Dawn; Medical Sciences
Background: The upper respiratory tract (URT) microbiome contributes to colonization resistance against respiratory pathogens such as Streptococcus pneumoniae, a causative agent of pneumonia. Bacterial pneumonia often begins with pathogen colonization in the URT before spreading to the lower airways. The resident microbiota serves as a first line of defense by competing for nutrients and space, as well as by producing antimicrobial compounds. We hypothesize that these microbiota-derived antimicrobial molecules can suppress pneumococcal growth and colonization. This study aimed to identify and characterize URT commensal bacteria with anti-S. pneumoniae activity and define bioactive products. Methods: A collection of nasal commensals from healthy adults was cultured and screened for antimicrobial activity against S. pneumoniae using agar-based inhibition assays. Active strains underwent activity-guided purification, liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) spectroscopy for structural elucidation of the bioactive molecule. Whole-genome analysis and comparative genomics were performed to identify relevant biosynthetic gene clusters (BGCs). Results: Over 2,000 bacterial isolates representing diverse URT taxa were assembled, and 48 strains from various genera exhibited anti-pneumococcal activity. Micrococcus luteus GC1842 showed potent inhibition of S. pneumoniae. The produced bioactive metabolites were identified as geninthiocin-family molecules, encoded by a unique thiopeptide BGC. These compounds inhibited S. pneumoniae with limited activity against other respiratory bacteria, suggesting a targeted mechanism which may contribute to minimizing microbiota disruption. Conclusions: We identify a human-associated M. luteus strain that produces a geninthiocin-like thiopeptide active against S. pneumoniae. Overall, findings demonstrate that colonization resistance in the URT is mediated by diverse commensal bacteria and distinct mechanisms, including thiopeptide antibiotics. We identify novel mechanisms of competition in the URT and expand the ecological and chemical scope of nasal commensals, prioritizing isolates with the potential to be developed into probiotics or postbiotic strategies that reinforce colonization resistance to prevent pneumococcal disease.
Defining a minimal symbiotic genome of the legume symbiont Sinorhizobium meliloti
(2026) Kearsley, Jason Vincent Shields; Finan, Turlough; Biology
Identifying and understanding bacterial genes involved in the formation of N2-fixing root nodules is of agricultural and environmental interest. Sinorhizobium meliloti is a model bacterium for studying the rhizobia-legume symbiosis. Most genes with direct functions in symbiotic nitrogen fixation (SNF) are harboured on two megaplasmids: pSymA (1354 kb) and pSymB (1683 kb). This thesis describes work on minimizing the pSymB replicon to establish a gene complement sufficient for a robust SNF phenotype. It also outlines my contribution towards establishing that 58 genes (63 kb) from pSymA are sufficient for a robust SNF phenotype. Megaplasmid pSymB is evolutionarily older and more chromosomal-like (i.e. a chromid) than the more recently acquired pSymA replicon. Both large-scale deletion analyses (top-down) and assembly-based methods (bottom-up) to minimize pSymB were conducted. These analyses revealed that minimizing pSymB results in a large symbiotic penalty. An initial minimization of pSymB to 261 kb (15%) resulted in SNF with a large degree of plant genotype-dependent variation. This served as a platform to demonstrate that additional regions housing undiscovered auxiliary genes are necessary for the efficient SNF. Accordingly, a minimized 673 kb replicating pSymB that facilitated consistent SNF was isolated. A cumulative deletion strategy refined this set to 276 kb (16% of pSymB) without further SNF impairment. In addition to the deletion approach, we developed a methodology that targeted the assembly of pSymB loci into discrete clusters followed by their iterative integration into a S. meliloti strain lacking pSymB. A set of 101 genes (114 kb) from pSymB proved capable of routinely forming nodules with SNF at 25% wild-type levels. By combining the minimized pSymA and iv pSymB sets, the smallest genome capable of forming root-nodule symbioses was established. This should serve as a powerful chassis for gain-of-function approaches to studying SNF.
Approved Minutes: February 2026 Graduate Council
(2026) School of Graduate Studies
Development of a checklist to assess the quality of electronic medical record data for research: An expert survey protocol survey questions
(2026-03-03) Schneider, Tyler; Holbrook, Anne
Clinical Pharmacology, Therapeutics and Toxicology High Priority Topics Across Core Clerkship Rotations
(2025-09-02) Gandhi, Bhavya; Khakban, Iliya; Bracken, Keyna; Levinson, Anthony J; Levine, Mitchell; Holbrook, Anne M; Medicine

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