Dataset Information

Augmented antibiotic resistance associated with cadmium induced alterations in Salmonella enterica serovar Typhi.

ABSTRACT: 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.

SUBMITTER: Kaur UJ

PROVIDER: S-EPMC6109086 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Augmented antibiotic resistance associated with cadmium induced alterations in Salmonella enterica serovar Typhi.

Kaur Ujjwal Jit UJ Preet Simran S Rishi Praveen P

Scientific reports 20180824 1

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) s ...[more]

PMID: 30143701

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Project description:Microbial horizontal gene transfer is a continuous process that shapes bacterial genomic adaptation to the environment and the composition of concurrent microbial ecology. This includes the potential impact of synthetic antibiotic utilization in farm animal production on overall antibiotic resistance issues; however, the mechanisms behind the evolution of microbial communities are not fully understood. We explored potential mechanisms by experimentally examining the relatedness of phylogenetic inference between multidrug-resistant Salmonella enterica serovar Typhimurium isolates and pathogenic Salmonella Typhimurium strains based on genome-wide single-nucleotide polymorphism (SNP) comparisons. Antibiotic-resistant S Typhimurium isolates in a simulated farm environment barely lost their resistance, whereas sensitive S Typhimurium isolates in soils gradually acquired higher tetracycline resistance under antibiotic pressure and manipulated differential expression of antibiotic-resistant genes. The expeditious development of antibiotic resistance and the ensuing genetic alterations in antimicrobial resistance genes in S Typhimurium warrant effective actions to control the dissemination of Salmonella antibiotic resistance.IMPORTANCE Antibiotic resistance is attributed to the misuse or overuse of antibiotics in agriculture, and antibiotic resistance genes can also be transferred to bacteria under environmental stress. In this study, we report a unidirectional alteration in antibiotic resistance from susceptibility to increased resistance. Highly sensitive Salmonella enterica serovar Typhimurium isolates from organic farm systems quickly acquired tetracycline resistance under antibiotic pressure in simulated farm soil environments within 2 weeks, with expression of antibiotic resistance-related genes that was significantly upregulated. Conversely, originally resistant S Typhimurium isolates from conventional farm systems lost little of their resistance when transferred to environments without antibiotic pressure. Additionally, multidrug-resistant S Typhimurium isolates genetically shared relevancy with pathogenic S Typhimurium isolates, whereas susceptible isolates clustered with nonpathogenic strains. These results provide detailed discussion and explanation about the genetic alterations and simultaneous acquisition of antibiotic resistance in S Typhimurium in agricultural environments.

Project description:Typhoid fever is an acute systemic infection of humans caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). In chronic carriers, the bacteria survive the harsh environment of the gallbladder by producing biofilm. The phenotype of S. Typhi biofilm cells is significantly different from the free-swimming planktonic cells, and studies have shown that they are associated with antibiotic resistance, immune system evasion, and bacterial persistence. However, the mechanism of this transition and the events leading to biofilm formation are unknown. High throughput sequencing was performed to identify the genes involved in biofilm formation and to postulate the mechanism of action.Planktonic S. Typhi cells were cultured using standard nutrient broth whereas biofilm cells were cultured in a stressful environment using high shearing-force and bile to mimic the gallbladder. Sequencing libraries were prepared from S. Typhi planktonic cells and mature biofilm cells using the Illumina HiSeq 2500 platform, and the transcriptome data obtained were processed using Cufflinks bioinformatics suite of programs to investigate differential gene expression between the two phenotypes. A total of 35 up-regulated and 29 down-regulated genes were identified. The identities of the differentially expressed genes were confirmed using NCBI BLAST and their functions were analyzed. The results showed that the genes associated with metabolic processes and biofilm regulations were down-regulated while those associated with the membrane matrix and antibiotic resistance were highly up-regulated.It is proposed that the biofilm phenotype of S. Typhi allows the bacteria to increase production of the membrane matrix in order to serve as a physical shield and to adhere to surfaces, and enter an energy conservation state in response to the stressful environment. Conversely, the planktonic phenotype allows the bacteria to produce flagella and increase metabolic activity to enable the bacteria to migrate and form new colonies of infection. This data provide a basis for further studies to uncover the mechanism of biofilm formation in S. Typhi and to discover novel genes or pathways associated with the development of the typhoid carrier state.

Dataset Information

Augmented antibiotic resistance associated with cadmium induced alterations in Salmonella enterica serovar Typhi.

Publications

Augmented antibiotic resistance associated with cadmium induced alterations in Salmonella enterica serovar Typhi.

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