Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment

Abstract

Conjugative plasmids often encode antibiotic resistance genes that provide selective advantages to their bacterial hosts during antibiotic treatment. Previous studies have predominantly considered these established genes as the primary benefit of antibiotic-mediated plasmid dissemination. However, many genes involved in cellular metabolic processes may also protect against antibiotic treatment and provide selective advantages. Despite the diversity of such metabolic genes and their potential ecological impact, their plasmid-borne prevalence, co-occurrence with canonical antibiotic resistance genes, and phenotypic effects remain widely understudied. To address this gap, we focused on Escherichia coli, which can often act as a pathogen, and is known to spread antibiotic resistance genes via conjugation. We characterized the presence of metabolic genes on 1,775 transferrable plasmids and compared their distribution to that of known antibiotic resistance genes. We found high abundance of genes involved in cellular metabolism and stress response. Several of these genes demonstrated statistically significant associations or disassociations with known antibiotic resistance genes at the strain level, indicating that each gene type may impact the spread of the other across hosts. Indeed, in vitro characterization of 13 statistically relevant metabolic genes confirmed that their phenotypic impact on antibiotic susceptibility was largely consistent with in situ relationships. These results emphasize the ecological importance of metabolic genes on conjugal plasmids, and that selection dynamics of E. coli pathogens arises as a complex consequence of both canonical mechanisms and their interactions with metabolic pathways.

Plasmid-Encoded Traits Vary across Environments

“…It could also be that plasmid accessory genes are influenced by interactions among the genes themselves. Indeed, a recent analysis of metabolic genes on conjugative plasmids of E. coli demonstrated statistically significant associations and disassociations with known antibiotic resistance genes at the strain level, suggesting that each gene type may impact the spread of the others across hosts ( 60 ). We caution, however, that the analysis here gives an approximation; our ability to test the role of host phylogeny is limited by the uneven data available across the phylogeny and environments.…”

A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut

“…These data revealed a large number of cases where pBI143 had identical SNV patterns in mother-infant pairs (Fig. 5A, Supplementary Table 10). A network analysis of shared SNV positions across metagenomes appeared to cluster family members more closely, indicating mother-infant pairs had more SNVs in common than they had with unrelated individuals, which we could further confirm by quantifying the relative distance between each sample to others (Supplementary Fig.…”

“…Plasmids are typically defined as extrachromosomal elements that replicate autonomously from the host chromosome [1][2][3][4] . In addition to being a workhorse for molecular biology, plasmids have been extensively studied for their ability to expedite microbial evolution 5 and enhance host fitness by providing properties such as antibiotic resistance, heavy metal resistance, virulence factors, or metabolic functions [6][7][8][9][10][11] .…”

A mathematician’s guide to plasmids: an introduction to plasmid biology for modellers

“…Plasmids may also encode resistance to other environmental dangers, such as heavy metals or other toxins [53][54][55]. A second large class of payload genes provide some new metabolic process [56,57]; this might include, for example, the ability to metabolize a new substrate for growth [58][59][60]. Virulence factors are also often found on plasmids [61].…”