The Phenotypic and Genotypic Landscape of Colicin Resistance
Adrienne Kicza, Christine Pureka, Diana Proctor, Margaret Riley and Robert Dorit
from: The Bacteriocins: Current Knowledge and Future Prospects (Edited by: Robert L. Dorit, Sandra M. Roy and Margaret A. Riley). Caister Academic Press, U.K. (2016) Pages: 141-154.
Abstract
This study explores the landscape of emergent resistance to bacteriocins, a class of naturally occurring protein antimicrobials. Specifically, we explore the resistance mechanisms that evolve in a sensitive strain of E. coli (BZB 1011), when exposed to a panel of 10 naturally occurring colicins, the characteristic, plasmid-encoded bacteriocins of E. coli. These colicins have been selected to represent the diversity of mechanisms underlying colicin binding, translocation and killing. We first determine the frequency with which resistance to each of these colicins arises, and assess the fitness cost of the resultant resistance. We subsequently examine the pattern of cross-resistance to other colicins exhibited by these resistant strains, and use that pattern to infer the probable mechanistic basis of the selected resistance. We confirm this phenotypic inference by examining the sequence-level changes that underlie selected cases of colicin resistance. We conclude that colicin resistance is usually acquired through a limited number of readily accessible routes. These pathways likely require one (or a small number) of mutational steps; they minimize the costs and maximize the benefits of resistance. The specific pathways, in turn, depend on the environment in which selection is occurring. When the selective landscape is experimentally perturbed by the addition of an aggressive iron-chelating agent (2,2, dipyridyl) to the medium, the cost of resistance, and hence the resulting preferred paths to resistance, are altered as well. These results suggest that the landscape of resistance acquisition may consist of a relatively small number of mappable routes of escape read more ...
