A toxin antitoxin system promotes the maintenance of the IncA/C-mobilizable Salmonella Genomic Island 1

Abstract

The multidrug resistance Salmonella Genomic Island 1 (SGI1) is an integrative mobilizable element identified in several enterobacterial pathogens. This chromosomal island requires a conjugative IncA/C plasmid to be excised as a circular extrachromosomal form and conjugally mobilized in trans. Preliminary observations suggest stable maintenance of SGI1 in the host chromosome but paradoxically also incompatibility between SGI1 and IncA/C plasmids. Here, using a Salmonella enterica serovar Agona clonal bacterial population as model, we demonstrate that a Toxin-Antitoxin (TA) system encoded by SGI1 plays a critical role in its stable host maintenance when an IncA/C plasmid is concomitantly present. This system, designated sgiAT for Salmonella genomic island 1 Antitoxin and Toxin respectively, thus seems to play a stabilizing role in a situation where SGI1 is susceptible to be lost through plasmid IncA/C-mediated excision. Moreover and for the first time, the incompatibility between SGI1 and IncA/C plasmids was experimentally confirmed.

Global phylogenomics of multidrug resistant Salmonella enterica serotype Kentucky ST198

“…Interestingly, the two isolates containing IncC plasmids did not carry the SGI. This observation is supported by many studies in the literature which have described the incompatibility of the SGI and IncC plasmids, as they share the same regulatory system (14,68,69).…”

The Variety in the Common Theme of Translation Inhibition by Type II Toxin–Antitoxin Systems

“…These elements are not only found in plasmids but also in other types of mobile genetic elements (such as phages and ICEs) as well as in chromosomes (see e.g., Anantharaman and Aravind, 2003;Pandey and Gerdes, 2005;Guglielmini and Van Melderen, 2011;Leplae et al, 2011;Ramisetty et al, 2016;Coray et al, 2017). While the roles of TAs, when located in mobile genetic elements, are reminiscent to that on plasmids, i.e., maintenance (Szekeres et al, 2007;Wozniak and Waldor, 2009;Huguet et al, 2016), the roles of chromosomally-encoded systems remains a largely debated topic in the field. These systems have been involved in the adaptation to adverse conditions and are considered to be stress response modules (Hayes and Van Melderen, 2011;Page and Peti, 2016;Harms et al, 2018), with a mainstream model proposing that TA systems are essential effectors of persistence to antibiotics (Gerdes and Maisonneuve, 2012).…”

The anti-Salmonella and immunostimulatory properties of yeast-based postbiotics in poultry and cattle

“…The probable loss of the integron is interesting when compared to other groups studying SGI-1 stability in Salmonella. These groups support the argument that the loss of the penta-resistant phenotype does not necessarily correlate with a loss of the integron after multiple passages (Huguet et al, 2016). In fact, experiments produced by these groups go even further and demonstrate that the loss of the integron is rare as it is nearly impossible to remove from the genome once it is inserted (Kiss, 2012).…”

“…contain an extraordinarily stable toxin-anti-toxin system (Huguet et al, 2016;Michael and Schwarz, 2016). The toxin-anti-toxin system prohibits the loss of the element once it is incorporated into the genome, thus enabling a sustained resistance to antibiotics (Huguet et al, 2016).…”

“…into an inert region of the Salmonella SGI-1 that is protected by the toxin-anti-toxin system, sgiTA (Huguet et al, 2016). We could then directly determine if the Salmonella population that persists within a flock has the integron but loses the phenotype, dies, or if the Salmonella completely loses the integron all together and persists.…”