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

1 , 2 , , 1

Scientific Reports

Nature Publishing Group UK

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      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.

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      Most cited references 52

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      Co-selection of antibiotic and metal resistance.

      There is growing concern that metal contamination functions as a selective agent in the proliferation of antibiotic resistance. Documented associations between the types and levels of metal contamination and specific patterns of antibiotic resistance suggest that several mechanisms underlie this co-selection process. These co-selection mechanisms include co-resistance (different resistance determinants present on the same genetic element) and cross-resistance (the same genetic determinant responsible for resistance to antibiotics and metals). Indirect but shared regulatory responses to metal and antibiotic exposure such as biofilm induction also represent potential co-selection mechanisms used by prokaryotes. Metal contamination, therefore, represents a long-standing, widespread and recalcitrant selection pressure with both environmental and clinical importance that potentially contributes to the maintenance and spread of antibiotic resistance factors.
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        Outer membrane permeability and antibiotic resistance.

        To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways.
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          Efflux-mediated heavy metal resistance in prokaryotes.

          What makes a heavy metal resistant bacterium heavy metal resistant? The mechanisms of action, physiological functions, and distribution of metal-exporting proteins are outlined, namely: CBA efflux pumps driven by proteins of the resistance-nodulation-cell division superfamily, P-type ATPases, cation diffusion facilitator and chromate proteins, NreB- and CnrT-like resistance factors. The complement of efflux systems of 63 sequenced prokaryotes was compared with that of the heavy metal resistant bacterium Ralstonia metallidurans. This comparison shows that heavy metal resistance is the result of multiple layers of resistance systems with overlapping substrate specificities, but unique functions. Some of these systems are widespread and serve in the basic defense of the cell against superfluous heavy metals, but some are highly specialized and occur only in a few bacteria. Possession of the latter systems makes a bacterium heavy metal resistant.
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            Author and article information

            Affiliations
            [1 ]ISNI 0000 0001 2174 5640, GRID grid.261674.0, Department of Microbiology, , Panjab University, ; Chandigarh, India
            [2 ]ISNI 0000 0001 2174 5640, GRID grid.261674.0, Department of Biophysics, , Panjab University, ; Chandigarh, India
            Contributors
            rishiparveen@pu.ac.in , rishipraveen@yahoo.com
            Journal
            Sci Rep
            Sci Rep
            Scientific Reports
            Nature Publishing Group UK (London )
            2045-2322
            24 August 2018
            24 August 2018
            2018
            : 8
            30143701
            6109086
            31143
            10.1038/s41598-018-31143-9
            © The Author(s) 2018

            Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

            Funding
            Funded by: FundRef https://doi.org/10.13039/501100001411, Indian Council of Medical Research (ICMR);
            Award ID: No. 5/3/3/9/2013-ECD-I
            Award Recipient :
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