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

Abstract

Summary Emergence and expansion of frequent multidrug‐resistant (MDR) major Salmonella clones/serotypes has been a significant threat in the last years. Metal compounds, such as copper, commonly used in animal‐production settings, have been pointed out as possible contributors for the selection of such strains/clones. However, the scarcity of studies limits our understanding of the impact of other metal environmental contaminants as arsenic (used in insecticides/herbicides/coccidiostats). We analysed arsenic tolerance (AsT) dispersion by phenotypic and genotypic (PCR/sequencing/I‐CeuI/S1/XbaI‐PFGE/hybridization) assays among Salmonella with diverse epidemiological and genetic backgrounds. Then, to better understand ars operon genetic contexts, the whole genome of five representative strains was sequenced. We found a high dispersion of ars operons conferring AsT, especially among copper‐tolerant and relevant serotypes/clones related to pig‐production setting. The acr3‐type was found dispersed in the chromosome of diverse serotypes, including the emergent S. Rissen. Conversely, arsBII was almost confined to the MDR ST34 European clone of S. Typhimurium/S. 4,[5],12:i:‐, always along with copper/silver tolerance sil + pco clusters in an integrative conjugative element. These data suggest that AsT is an essential adaptive feature for the ecological success of these epidemic clones/serotypes and alerts for global strategies to reduce arsenic‐based compounds' impact thus preventing environmental/food contamination with frequent MDR foodborne pathogens.

The Role of Salmonella Genomic Island 4 in Metal Tolerance of Salmonella enterica Serovar I 4,[5],12:i:- Pork Outbreak Isolate USDA15WA-1

“…Other investigators have also suggested that the acquisition of metal tolerance genes is attributed to the use of metals (e.g., zinc and copper) as antimicrobial agents in human healthcare or in agriculture, and this practice has potentially contributed to the emergence of clinically relevant Salmonella isolates by aiding their survival in metal-contaminated settings, such as swine production [60,61]. Mourao et al suggested that acquisition of the arsenic resistance gene arsBII by Salmonella I 4, [5],12:i:has resulted in a foodborne pathogen resistant to arsenic compounds used in insecticides, herbicides, and coccidiostats [62]. Furthermore, a comparative whole-genome analysis of 50 epidemiologically unrelated serovar I 4, [5],12:i:-isolates from Italy revealed the widespread presence of heavy metal tolerance gene cassettes, with most of the Salmonella strains containing copper and silver resistance genes and half of the isolates also containing the mercury tolerance gene merA [7].…”

Genomic Evidence of Environmental and ResidentSalmonellaSenftenberg and Montevideo Contamination in the Pistachio Supply-chain

“…This island has previously been shown to increase the ability of a bacterium to survive in an environment with higher levels of copper and silver, as well as the ability to provide tolerance during the transition between aerobic and anaerobic environments, affording a fitness advantage for facultative anaerobes (43, 45). The use of copper as a growth promoter in swine and poultry has led to the selection of this island in Salmonella associated with these sources in other countries (46, 47). The use of copper as a fungicide and bactericide in agriculture has been reported for many years, and it is generally considered safe for both conventional and organic produce use (48, 49).…”

Atypical Non-H2S-Producing Monophasic Salmonella Typhimurium ST3478 Strains from Chicken Meat at Processing Stage Are Adapted to Diverse Stresses

“…The S . 1,4,[5],12:i:- poultry isolates presented the typical antibiotic resistance ( bla TEM + strA-strB + sul2 ± tetB ) and metal tolerance ( pcoD + silA + arsB ± merA ) features of the widespread clinically relevant European clone (ST34) [ 16 , 17 ]. Resistance to the tested antibiotics and tolerance to copper (MICs = 32 mM) was restricted to S .…”

“…1,4,[5],12:i:- copper tolerant strains might also have the ability to escape the metal-mediated antimicrobial response of human macrophages [ 70 ]. In the context of antibiotic reducing/replacing, the extensive use of heavy metals for animal growth promotion (copper and zinc) as well as mercury and arsenic compounds accumulation in the agriculture environment [ 17 ], might be potential factors contributing to the persistence and expansion of this emerging S . 1,4,[5],12:i:- ST3478 clonal lineage.…”

“…The search of EU-targeted Salmonella serotypes (Enteritidis, Typhimurium and 4,[ 5 ],12:i:-) [ 15 ] and their antibiotic resistance ( bla TEM , cmlA1 - catA - floR , strA - strB - aadA-aac(3) -IV- aphA1 , sul1 - sul2 - sul3 , tetA - tetB , dfrA1 - dfrA12 - dfrA17 ) and metal tolerance ( pcoD , silA , merA , arsB and terF ) markers was performed by standard PCRs ( Table S1 ) in all isolates recovered from positive chicken meat samples [ 16 , 17 , 18 ].…”