Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer

Abstract

The emergence and spread of antibiotic resistance among pathogenic bacteria has been a rising problem for public health in recent decades. It is becoming increasingly recognized that not only antibiotic resistance genes (ARGs) encountered in clinical pathogens are of relevance, but rather, all pathogenic, commensal as well as environmental bacteria-and also mobile genetic elements and bacteriophages-form a reservoir of ARGs (the resistome) from which pathogenic bacteria can acquire resistance via horizontal gene transfer (HGT). HGT has caused antibiotic resistance to spread from commensal and environmental species to pathogenic ones, as has been shown for some clinically important ARGs. Of the three canonical mechanisms of HGT, conjugation is thought to have the greatest influence on the dissemination of ARGs. While transformation and transduction are deemed less important, recent discoveries suggest their role may be larger than previously thought. Understanding the extent of the resistome and how its mobilization to pathogenic bacteria takes place is essential for efforts to control the dissemination of these genes. Here, we will discuss the concept of the resistome, provide examples of HGT of clinically relevant ARGs and present an overview of the current knowledge of the contributions the various HGT mechanisms make to the spread of antibiotic resistance.

Keywords: GTA; antibiotic resistance; conjugation; gene transfer agents; lateral gene transfer; resistome; transduction; transformation.

Figure 1

Mechanisms of horizontal gene transfer. Each quadrant represents one different method of gene transfer. (A) Conjugation is a process requiring cell to cell contact via cell surface pili or adhesins, through which DNA is transferred from the donor cell to the recipient cell. (B) Transformation is the uptake, integration, and functional expression of naked fragments of extracellular DNA. (C) Through specialized or generalized transduction, bacteriophages may transfer bacterial DNA from a previously infected donor cell to the recipient cell. During generalized transduction, bacterial DNA may be accidentally loaded into the phage head (shown as a phage with a red DNA strand). During specialized transduction, genomic DNA neighboring the prophage DNA is co-excised and loaded into a new phage (not shown). (D) Gene transfer agents (GTAs) are bacteriophage-like particles that carry random pieces of the producing cell's genome. GTA particles may be released through cell lysis and spread to a recipient cell.