摘要

鉴于关于金属和抗生素抗性共同选择的报道，最近我们报道了伤寒沙门氏菌Ty2中镉的积累增加导致抗生素耐药性增加。继续进行本研究以证实临床分离株中的这种关联。有趣的是，在临床分离株中发现镉水平更高，这与其抗生素敏感性/抗性模式相关。在镉积累时，抗生素敏感的分离株具有抗性，并且抗性分离株根据其最小抑制浓度变得更具抗性。此外，在使病原体经历镉积累之后，评估细胞中发生的改变。跨代镉暴露导致生长反应，形态，蛋白质组，除SOD以外的抗氧化剂升高，生物膜形成增加，细胞内巨噬细胞杀伤减少以及编码金属硫蛋白和金属转运蛋白的基因上调。因此，这些结果表明，如果从环境中获得的镉是不可降解的，则可以对宿主中的沙门氏菌施加持久的选择压力，这可能在以后显示出抗生素抗性，这是共同选择的结果。因此，需要开发适当的策略来抑制重金属的这种持久压力，因为这些是病原体中新出现的抗生素抗性的因素之一。

In view of the reports on co-selection of metal and antibiotic resistance, recently we have reported that increased cadmium accumulation in Salmonella Typhi Ty2 leads to increased antibiotic resistance. In continuation, the present study was carried to substantiate this association in clinical isolates. Interestingly, the levels of cadmium were found to be more in the clinical isolates which co-related with their antibiotic sensitivity/resistance pattern. On cadmium accumulation, antibiotic(s) sensitive isolates were rendered resistant and the resistant isolates were rendered more resistant as per their minimum inhibitory concentration(s). Further, after subjecting the pathogen to cadmium accumulation, alterations occurring in the cells were assessed. Transgenerational cadmium exposure led to changes in growth response, morphology, proteome, elevated antioxidants other than SOD, increased biofilm formation, decreased intracellular macrophage killing coupled with upregulation of genes encoding metallothionein and metal transporters. Thus, these results indicate that cadmium, if acquired from the environment, being non-degradable can exert a long-lasting selective pressure on Salmonella in the host which may display antibiotic resistance later on, as a result of co-selection. Therefore, appropriate strategies need to be developed to inhibit such an enduring pressure of heavy metals, as these represent one of the factors for the emerging antibiotic resistance in pathogens.

https://www.ncbi.nlm.nih.gov/pubmed/30143701