A Comparative Genomic Analysis Provides Novel Insights Into the Ecological Success of the Monophasic Salmonella Serovar 4,[5],12:i:-

Abstract

Over the past decades, Salmonella 4,[5],12:i:- has rapidly emerged and it is isolated with high frequency in the swine food chain. Although many studies have documented the epidemiological success of this serovar, few investigations have tried to explain this phenomenon from a genetic perspective. Here a comparative whole-genome analysis of 50 epidemiologically unrelated S. 4,[5],12:i:-, isolated in Italy from 2010 to 2016 was performed, characterizing them in terms of genetic elements potentially conferring resistance, tolerance and persistence characteristics. Phylogenetic analyses indicated interesting distinctions among the investigated isolates. The most striking genetic trait characterizing the analyzed isolates is the widespread presence of heavy metals tolerance gene cassettes: most of the strains possess genes expected to confer resistance to copper and silver, whereas about half of the isolates also contain the mercury tolerance gene merA. A functional assay showed that these genes might be useful for preventing the toxic effects of metals, thus supporting the hypothesis that they can contribute to the success of S. 4,[5],12:i:- in farming environments. In addition, the analysis of the distribution of type II toxin-antitoxin families indicated that these elements are abundant in this serovar, suggesting that this is another factor that might favor its successful spread.

Pathogenicity and Competitive Fitness of Salmonella enterica Serovar 4,[5],12:i:- Compared to Salmonella Typhimurium and Salmonella Derby in Swine

“…Although S. 4, [5],12:i:has been reported more frequently, additional research is needed to evaluate the specifics of its pathogenicity in swine. Based on published research using multiple-locus variable number tandem repeat analysis (MLVA), phage typing, pulsed-field gel electrophoresis (PFGE), polymerase chain reaction (PCR), and whole-genome sequencing (WGS), it is highly likely that S. 4, [5],12:i:-is a monophasic variant of S. Typhimurium (9)(10)(11)(12)(13)(14)(15)(16). Thus, S. 4, [5],12:i:-could resemble the disease-causing ability of S. Typhimurium.…”

“…Salmonella 4, [5],12:i:-has repeatedly been reported to be more highly resistant to antimicrobials relative to S. Typhimurium (6,31,32), which may provide a significant advantage to its survival in swine operations with extensive antimicrobial drug use. Likewise, S. 4, [5],12:i:-is commonly resistant to heavy metals such as zinc and copper, which can be added to livestock feeds as an alternative to antibiotics to reduce bacterial infections (16,33). With the antimicrobial properties of some heavy metals, it is evident that resistance to them may provide a selective advantage over more susceptible serovars.…”

Tolerance to arsenic contaminant among multidrug‐resistant and copper‐tolerant Salmonella successful clones is associated with diverse ars operons and genetic contexts

“…AsT genes are widely spread in environmental Gramnegative bacteria (e.g., Herminiimonas arsenicoxydans, Pantoea sp., Cupriavidus metallidurans, Pseudomonas putida) (Muller et al, 2007;Fernández et al, 2014;Wang et al, 2016) and some foodborne pathogens (e.g. Salmonella and Campylobacter) (Joerger et al, 2010;Noormohamed and Fakhr, 2013;Mastrorilli et al, 2018;Figueiredo et al, 2019). However, in the case of Salmonella, only arsBI/II genes were searched, with their distribution among epidemic strains/clones scarcely known due to the limited number of isolates and clones/ serotypes included in different studies (Joerger et al, 2010;Petrovska et al, 2016;Mastrorilli et al, 2018;Figueiredo et al, 2019).…”

“…Salmonella and Campylobacter) (Joerger et al, 2010;Noormohamed and Fakhr, 2013;Mastrorilli et al, 2018;Figueiredo et al, 2019). However, in the case of Salmonella, only arsBI/II genes were searched, with their distribution among epidemic strains/clones scarcely known due to the limited number of isolates and clones/ serotypes included in different studies (Joerger et al, 2010;Petrovska et al, 2016;Mastrorilli et al, 2018;Figueiredo et al, 2019). Here, high dispersion of ars operons, particularly acr3-type, was demonstrated and especially detected among copper-tolerant relevant serotypes/clones related to the pig-production setting.…”

“…Additional genes such as arsA (coding for P1B-type ATPase that binds to arsB/acr3 helping in As[III] efflux) and arsD (weak As[III]-responsive transcriptional regulator and metallochaperone) could also be present (Andres and Bertin, 2016;Yang and Rosen, 2016). Previous reports have described the presence of the arsB-type operon in a few plasmid families (García- Fernández and Carattoli, 2010;Abraham et al, 2016;Zhang et al, 2018) and in the chromosome of Salmonella (Petrovska et al, 2016;Mastrorilli et al, 2018;Branchu et al, 2019) and other Gram-negative bacteria (Andres and Bertin, 2016;Yang and Rosen, 2016), particularly in environmental ones (e.g., Pantoea sp., Herminiimonas arsenicoxydans, Cupriavidus metallidurans) (Muller et al, 2007;Zhang et al, 2009;Cai et al, 2013;Wang et al, 2016). Contrarily, the acr3-type operon although also found in bacteria is widely dispersed in archaea and eukaryotes (fungi and lower plants) associated both with plasmids and the chromosome (Argudín et al, 2019).…”