Horizontal Transfer of the Salmonella enterica Serovar Infantis Resistance and Virulence Plasmid pESI to the Gut Microbiota of Warm-Blooded Hosts

Abstract

Salmonella enterica serovar Infantis is one of the prevalent salmonellae worldwide. Recently, we showed that the emergence of S. Infantis in Israel was facilitated by the acquisition of a unique megaplasmid (pESI) conferring multidrug resistance and increased virulence phenotypes. Here we elucidate the ecology, transmission properties, and regulation of pESI. We show that despite its large size (~280 kb), pESI does not impose a significant metabolic burden in vitro and that it has been recently fixed in the domestic S. Infantis population. pESI conjugation and the transcription of its pilus (pil) genes are inhibited at the ambient temperature (27°C) and by ≥1% bile but increased under temperatures of 37 to 41°C, oxidative stress, moderate osmolarity, and the microaerobic conditions characterizing the intestinal environment of warm-blooded animals. The pESI-encoded protein TraB and the oxygen homeostasis regulator Fnr were identified as transcriptional regulators of pESI conjugation. Using the mouse model, we show that following S. Infantis infection, pESI can be horizontally transferred to the gut microbiota, including to commensal Escherichia coli strains. Possible transfer, but not persistence, of pESI was also observed into Gram-positive mouse microbiota species, especially Lactobacillus reuteri. Moreover, pESI was demonstrated to further disseminate from gut microbiota to S. enterica serovar Typhimurium, in the context of gastrointestinal infection. These findings exhibit the ability of a selfish clinically relevant megaplasmid to distribute to and from the microbiota and suggest an overlooked role of the microbiota as a reservoir of mobile genetic elements and intermediator in the spread of resistance and virulence genes between commensals and pathogenic bacteria.

Regulation of conjugative transfer of plasmids and integrative conjugative elements

“…Since the 1960s, plasmids carrying antibiotic resistance genes have continuously gained interest (Wyrsch et al, 2016), moreover, pollution in different regions of the planet has led to the discovery and description of plasmids involved in metal resistance (Aminov, 2011). Plasmids involved in pathogenic (Aviv et al, 2016;Lang and Faure, 2014) and symbiotic interactions are also widely known (Romero and Brom, 2004). Similar to chromosomal genetic information, a high proportion of genes encoding proteins with unknown function is also found in plasmids (Koonin, 2016).…”

“…A different regulatory system has been described for pESI from Salmonella enterica sv infantis (Aviv et al, 2016). This plasmid is responsible for foodborne infections and confers multidrug resistance and virulence.…”

“…Interestingly, transfer of this plasmid is modulated by conditions reminiscent of those present in the intestines of animals, such as temperature, oxidative stress and moderate osmolarity. The elements involved in the transcriptional regulation of pESI transfer are TraB and an oxygen homeostasis regulator, Fnr (Aviv et al, 2016).…”

Detection and characterization of multidrug‐resistant Salmonella enterica serovar Infantis as an emerging threat in poultry farms of Faisalabad, Pakistan

“…Infantis is the sixth most common prevalent bacteria in food animals while in Europe, it has been ranked as third, after S. Enteritidis and S. Typhimurium with an increased prevalence from 1 to 2Á5% in 2010 (Aviv et al 2016). In contrast to the time-consuming and complicated serotypic Salmonella detection methods, molecular techniques like polymerase chain reaction (PCR), due to its sensitivity, specificity and rapidity give better detection of Salmonella serovars (Hong et al 2008).…”

Integrity and stability of virulence plasmids fromPseudomonas syringaeare modulated by mobile genetic elements and multiple toxin-antitoxin systems

“…Plasmids are dispensable extrachromosomal elements widely distributed in bacteria, facilitating their survival and the colonization of eukaryotic hosts [1][2][3][4]. The plasticity and transmissibility of plasmids contribute to a rapid dissemination of resistance and virulence genes, thus promoting the emergence of uncontrollable bacterial diseases, both in clinical and agricultural settings [5][6][7][8][9]. However, plasmids are usually large and exist in several copies per cell, potentially imposing a significant metabolic burden to the cell, which might facilitate the emergence of plasmid-free derivatives in the absence of selection for plasmid-borne characters [8,10,11].…”