Bacterial Responses and Genome Instability Induced by Subinhibitory Concentrations of Antibiotics.

Arnaud Gutierrez,Ivan Matic,Luisa Laureti

doi:10.3390/antibiotics2010100

Abstract

Nowadays, the emergence and spread of antibiotic resistance have become an utmost medical and economical problem. It has also become evident that subinhibitory concentrations of antibiotics, which pollute all kind of terrestrial and aquatic environments, have a non-negligible effect on the evolution of antibiotic resistance in bacterial populations. Subinhibitory concentrations of antibiotics have a strong effect on mutation rates, horizontal gene transfer and biofilm formation, which may all contribute to the emergence and spread of antibiotic resistance. Therefore, the molecular mechanisms and the evolutionary pressures shaping the bacterial responses to subinhibitory concentrations of antibiotics merit to be extensively studied. Such knowledge is valuable for the development of strategies to increase the efficacy of antibiotic treatments and to extend the lifetime of antibiotics used in therapy by slowing down the emergence of antibiotic resistance.

Highlights

With the early breakthroughs of Fleming and Waksman, the discovery of novel natural antibacterial compounds with important pharmaceutical applications revolutionized medicine and experienced an exponential phase, especially between 1950s and 1960s, the so called “Golden Age”
We recently showed that in E. coli, subinhibitory concentrations of different bactericidal antibiotics stimulate the induction of the general stress response, which is controlled by the RpoS sigma factor [15]
The alternative sigma factor RpoS is conserved in many bacterial species and controls the expression of many genes involved in cell shape determination, stress response, biofilm formation, DNA repair, metabolism or genes coding for virulence factors [22]

Summary

Introduction

With the early breakthroughs of Fleming and Waksman, the discovery of novel natural antibacterial compounds with important pharmaceutical applications revolutionized medicine and experienced an exponential phase, especially between 1950s and 1960s, the so called “Golden Age”. It soon became evident that bacterial resistance can be acquired through mutations or horizontal gene transfers [1]. The worldwide spread of antibiotic resistance is a major healthcare and economic problem because it directly challenges our ability to treat infectious diseases. To extend the lifetime of current and future antibiotic-based therapies, it is increasingly urgent to enlarge our knowledge of how new antibiotic resistances emerge and spread in bacterial population. We will firstly focus on the bacterial responses to subinhibitory concentrations of antibiotics, with particular emphasis on the induction of the SOS and RpoS regulons. We will describe how subinhibitory concentrations of antibiotics promote genetic variation by increasing the rates of horizontal gene transfer and mutations. We will discuss how these molecular mechanisms are directly responsible for the emergence and the spread of resistance determinants

Antibiotics

Bacterial Responses to Subinhibitory Concentrations of Antibiotics

Subinhibitory Concentrations of Antibiotics Enhance Horizontal Gene Transfer

Findings

Concluding Remarks