The evolution of contact-dependent inhibition in non-growing populations ofEscherichia coli

Abstract

In the course of liquid culture, serial passage experiments with Escherichia coli K-12 bearing a mutator gene deletion (DmutS) we observed the evolution of strains that appeared to kill or inhibit the growth of the bacteria from where they were derived, their ancestors. We demonstrate that this inhibition occurs after the cells stop growing and requires physical contact between the evolved and ancestral bacteria. Thereby, it is referred to as stationary phase contact-dependent inhibition (SCDI ). The evolution of this antagonistic relationship is not anticipated from existing theory and experiments of competition in mass (liquid) culture. Nevertheless, it occurred in the same way (parallel evolution) in the eight independent serial transfer cultures, through different single base substitutions in a gene in the glycogen synthesis pathway, glgC. We demonstrate that the observed mutations in glgC, which codes for ADP-glucose pyrophosphorylase, are responsible for both the ability of the evolved bacteria to inhibit or kill their ancestors and their immunity to that inhibition or killing. We present evidence that without additional evolution, mutator genes, or known mutations in glgC, other strains of E. coli K-12 are also capable of SCDI or sensitive to this inhibition. We interpret this, in part, as support for the generality of SCDI and also as suggesting that the glgC mutations responsible for the SCDI, which evolved in our experiments, may suppress the action of one or more genes responsible for the sensitivity of E. coli to SCDI. Using numerical solutions to a mathematical model and in vitro experiments, we explore the population dynamics of SCDI and postulate the conditions responsible for its evolution in mass culture. We conclude with a brief discussion of the potential ecological significance of SCDI and its possible utility for the development of antimicrobial agents, which unlike existing antibiotics, can kill or inhibit the growth of bacteria that are not growing.

Proximity-Dependent Inhibition in Escherichia coli Isolates from Cattle

“…A single base substitution in a regulatory enzyme that catalyzes glycogen synthesis allows the mutant strains to kill or inhibit growth of nonmutant strains. This mutation also provides immunity for the mutant strain (17). A similar stationaryphase inhibition was observed in another mutant E. coli mutant in which a mutation in uup, a gene that encodes a soluble ATP-binding cassette, rendered the mutant strain sensitive to its parental strain when in close proximity (19).…”

“…The requirement for close cell-to-cell proximity is not uncommon for cell signaling, but contact-dependent inhibition has only been identified recently (1,17,19). Aoki et al (1) first observed contact-dependent inhibition in uropathogenic E. coli (EC93).…”

Culture History and Population Heterogeneity as Determinants of Bacterial Adaptation: the Adaptomics of a Single Environmental Transition

“…A phenomenon called "contact-dependent growth inhibition" (CDI) was described, in which a uropathogenic E. coli strain produced a significant reduction in the number of viable E. coli K-12 cells (7). Other contact-dependent phenomena in different bacteria have been described (82,128,174,226,228,331).…”

Evidence for Broad-Spectrum Biofilm Inhibition by the Bacterium Bacillus sp. Strain SW9

“…Aoki et al (10) inhibition system in which certain pathogenic Escherichia coli strains bound to and inhibited the growth of susceptible target cells within a mixed bacterial population. Recently, such growth inhibition has been identified in some other strains (16)(17)(18). However, the present work is the first known report on the system of contact-dependent biofilm inhibition without growth defects.…”