Leaky resistance and the conditions for the existence of lytic bacteriophage

• Type of Material: Article
• Authors: Waqas N. Chaudhry, Emory University; Maros Pleska, Institute of Science and Technology Austria; Nilang N. Shah, Emory University; Howard Weiss, Georgia Institute of Technology; Ingrid C. McCall, Emory University; Justin R. Meyer, University of California San Diego; Animesh Gupta, University of California San Diego; Calin C. Guet, Institute of Science and Technology Austria; Bruce Levin, Emory University
• Language: English
• Date: 2018-08-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Chaudhry et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pbio.2005971
• Title of Journal or Parent Work: PLoS Biology
• ISSN: 1544-9173
• Volume: 16
• Issue: 8
• Start Page: e2005971
• End Page: e2005971
• Grant/Funding Information: Human Frontier Science Program (grant number RGY0079/2011); received by CCG.; Georgia Technical University; stipend support received by WNC.; Austrian Academy of Science. DOC Fellowship received by MP.; The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; US National Institutes of Health (grant number R01GM091875); received by BRL.
• Keywords: PSEUDOMONAS-AERUGINOSA; EVOLUTIONARY DYNAMICS; TRADE-OFFS; VIBRIO-CHOLERAE; Life Sciences & Biomedicine - Other Topics; Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Biology; POPULATION; ANTAGONISTIC COEVOLUTION; COEXISTENCE; ESCHERICHIA-COLI K-12; HOST; PHAGE
• Research Categories: Biology, Molecular; Chemistry, Biochemistry

Abstract

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”.