Population analysis of heavy metal and biocide resistance genes in Salmonella enterica from human clinical cases in New Hampshire, United States.

Microbes frequently encounter heavy metals and other toxic compounds generated from natural biogeochemical processes and anthropogenic activities. Here, we analyzed the prevalence and association of genes conferring resistance to heavy metals, biocides, and antimicrobial compounds in 394 genome sequences of clinical human-derived S. enterica from New Hampshire, USA. The most prevalent was the gold operon (gesABC-golTSB), which was present in 99.2% of the genomes. In contrast, the other five heavy metal operons (arsenic, copper, mercury, silver, tellurite) were present in 0.76% (3/394)–5.58% (22/394) of the total population. The heavy metal operons and three biocide resistance genes were differentially distributed across 15 sequence types (STs) and 16 serotypes. The number of heavy metal operons and biocide resistance genes per genome was significantly associated with high number of antimicrobial resistance (AMR) genes per genome. Notable is the mercury operon which exhibited significant association with genes conferring resistance to aminoglycosides, cephalosporins, diaminopyrimidine, sulfonamide, and fosfomycin. The mercury operon was co-located with the AMR genes aac(3)-IV, ant(3”)-IIa, aph(3’)-Ia, and aph(4)-Ia, CTX-M-65, dfrA14, sul1, and fosA3 genes within the same plasmid types. Lastly, we found evidence for negative selection of individual genes of each heavy metal operon and the biocide resistance genes (dN/dS < 1). Our study highlights the need for continued surveillance of S. enterica serotypes that carry those genes that confer resistance to heavy metals and biocides that are often associated with mobile AMR genes. The selective pressures imposed by heavy metals and biocides on S. enterica may contribute to the co-selection and spread of AMR in human infections.

微生物经常会遇到由自然生物地球化学过程和人类活动产生的重金属及其他有毒化合物。在此，我们分析了美国新罕布什尔州394株临床人源肠道沙门氏菌基因组序列中赋予对重金属、杀菌剂和抗菌化合物抗性的基因的流行情况及其关联。最普遍的是金操纵子（gesABC - golTSB），它存在于99.2%的基因组中。相比之下，其他五种重金属操纵子（砷、铜、汞、银、碲酸盐）在总群体中的存在比例为0.76%（3/394） - 5.58%（22/394）。重金属操纵子和三种杀菌剂抗性基因在15种序列型（STs）和16种血清型中差异分布。每个基因组中重金属操纵子和杀菌剂抗性基因的数量与每个基因组中大量的抗菌药物抗性（AMR）基因显著相关。值得注意的是汞操纵子，它与赋予对氨基糖苷类、头孢菌素类、二氨基嘧啶类、磺胺类和磷霉素抗性的基因显著相关。汞操纵子与AMR基因aac(3)-IV、ant(3”)-IIa、aph(3’)-Ia、aph(4)-Ia、CTX - M - 65、dfrA14、sul1和fosA3基因位于同一质粒类型内。最后，我们发现了每个重金属操纵子的单个基因和杀菌剂抗性基因存在负选择的证据（dN/dS < 1）。我们的研究强调了需要持续监测携带那些赋予对重金属和杀菌剂抗性基因的肠道沙门氏菌血清型，这些基因通常与可移动的AMR基因相关。重金属和杀菌剂对肠道沙门氏菌施加的选择压力可能导致AMR在人类感染中的共选择和传播。