Poster abstracts
Poster number 107 submitted by Carlos Owusu-Ansah
Genetic targets predict metabolic phenotypes of phage resistance mutations
Carlos Owusu-Ansah (Biophysics Graduate Program), Marion Urvoy (Department of Microbiology, Ohio State University), Garrett Smith (Department of Microbiology, Ohio State University), Karna Gowda, Matthew Sullivan (Department of Microbiology, Ohio State University)
Abstract:
Microbial life is shaped by the tension between bottom-up nutrient competition and top-down viral predation. While recent discoveries of diverse intracellular defense systems have transformed our understanding of the arms race, resistance mutations that prevent phage entry by altering the cell envelope remain a fundamental survival strategy with profound metabolic consequences. Yet, predicting the environmental dependence of these fitness costs remains a challenge. Previous studies report varying patterns, with fitness costs that either increase under nutrient limitation or remain constant. Here, we propose a mechanistic framework linking the genetic target of resistance to its metabolic consequences. Specifically, we distinguish between two contrasting classes: Type I mutations target nutrient transporters, reducing nutrient uptake and creating a "starvation" phenotype that is typically costly under nutrient limitation. Type II mutations target biosynthetic enzymes, reducing flux capacity and creating an "overflow" phenotype that is typically costly under nutrient excess. We examine this framework using growth data from a panel of phage-resistant Cellulophaga baltica mutants, focusing on one carrying a missense mutation in glmM, a key cell envelope enzyme. By integrating experimental growth data with genome-scale metabolic modeling, we show that this Type II bottleneck forces organic carbon secretion and imposes a fitness cost that diminishes in low-nutrient environments. Finally, we identify targeted metabolic supplementation strategies to alleviate the bottleneck. This framework provides a predictive link between the genetic target of a resistance mutation and its metabolic phenotype, offering new insights into environment-dependent coevolution and phage-driven community cross-feeding.
Keywords: Phage resistance, Microbes, Metabolism