Dataset Information

The ancestry of insertion sequences common to Escherichia coli and Salmonella typhimurium.

ABSTRACT: Despite very restricted gene exchange between Escherichia coli and Salmonella typhimurium, both species harbor several of the same classes of insertion sequences. To determine whether the present-day distribution of these transposable elements is due to common ancestry or to horizontal transfer, we determined the sequences of IS1 and IS200 from natural isolates of S. typhimurium and E. coli. One strain of S. typhimurium harbored an IS1 element identical to that originally recovered from E. coli, suggesting that the element was recently transferred between these two species. The level of sequence divergence between copies of IS200 from E. coli and S. typhimurium ranged from 9.5 to 10.7%, indicating that IS200, unlike IS1, has not been repeatedly transferred between these enteric species since E. coli and S. typhimurium diverged from a common ancestor. Levels of variability in IS1 and IS200 for strains of E. coli and S. typhimurium show that each class of insertion sequence has a characteristic pattern of transposition within and among host genomes.

SUBMITTER: Bisercic M

PROVIDER: S-EPMC206963 | biostudies-other | 1993 Dec

REPOSITORIES: biostudies-other

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The ancestry of insertion sequences common to Escherichia coli and Salmonella typhimurium.

Bisercić M M Ochman H H

Journal of bacteriology 19931201 24

Despite very restricted gene exchange between Escherichia coli and Salmonella typhimurium, both species harbor several of the same classes of insertion sequences. To determine whether the present-day distribution of these transposable elements is due to common ancestry or to horizontal transfer, we determined the sequences of IS1 and IS200 from natural isolates of S. typhimurium and E. coli. One strain of S. typhimurium harbored an IS1 element identical to that originally recovered from E. coli, ...[more]

PMID: 8253675

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Project description:In the fight against antibiotic resistance, drugs that target resistance mechanisms in bacteria can be used to restore the therapeutic effectiveness of antibiotics. The multidrug resistance efflux complex AcrAB-TolC is the most clinically relevant efflux pump in Enterobacterales and is a target for drug discovery. Inhibition of the pump protein AcrB allows the intracellular accumulation of a wide variety of antibiotics, effectively restoring their therapeutic potency. To facilitate the development of AcrB efflux inhibitors, it is desirable to discover the native substrates of the pump, as these could be chemically modified to become inhibitors. We analyzed the native substrate profile of AcrB in Escherichia coli MG1655 and Salmonella enterica serovar Typhimurium SL1344 using an untargeted metabolomics approach. We analyzed the endo- and exometabolome of the wild-type strain and their respective AcrB loss-of-function mutants (AcrB D408A) to determine the metabolites that are native substrates of AcrB. Although there is 95% homology between the AcrB proteins of S. Typhimurium and E. coli, we observed mostly different metabolic responses in the exometabolomes of the S. Typhimurium and E. coli AcrB D408A mutants relative to those in the wild type, potentially indicating a differential metabolic adaptation to the same mutation in these two species. Additionally, we uncovered metabolite classes that could be involved in virulence of S. Typhimurium and a potential natural substrate of AcrB common to both species.IMPORTANCE Multidrug-resistant Gram-negative bacteria pose a global threat to human health. The AcrB efflux pump confers inherent and evolved drug resistance to Enterobacterales, including Escherichia coli and Salmonella enterica serovar Typhimurium. We provide insights into the physiological role of AcrB: (i) we observe that loss of AcrB function in two highly related species, E. coli and S. Typhimurium, has different biological effects despite AcrB conferring drug resistance to the same groups of antibiotics in both species, and (ii) we identify potential natural substrates of AcrB, some of which are in metabolite classes implicated in the virulence of S. Typhimurium. Molecules that inhibit multidrug efflux potentiate the activity of old, licensed, and new antibiotics. The additional significance of our research is in providing data about the identity of potential natural substrates of AcrB in both species. Data on these will facilitate the discovery of, and/or could be chemically modified to become, new efflux inhibitors.

Dataset Information

The ancestry of insertion sequences common to Escherichia coli and Salmonella typhimurium.

Publications

The ancestry of insertion sequences common to Escherichia coli and Salmonella typhimurium.

Similar Datasets

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