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Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

ABSTRACT: Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.

SUBMITTER: Di Venanzio G

PROVIDER: S-EPMC6591400 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Di Venanzio Gisela G Flores-Mireles Ana L AL Calix Juan J JJ Haurat M Florencia MF Scott Nichollas E NE Palmer Lauren D LD Potter Robert F RF Hibbing Michael E ME Friedman Laura L Wang Bin B Dantas Gautam G Skaar Eric P EP Hultgren Scott J SJ Feldman Mario F MF

Nature communications 20190624 1

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries th ...[more]

PMID: 31235751

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Project description:The opportunistic pathogen A. baumannii has a remarkable capacity to persist in the hospital environment and cause devastating human infections. This capacity can be attributed partly to the sensing and regulatory systems that enable this pathogen to modify its physiology based on environmental cues. One of the signals that A. baumannii senses and responds to is light through the sensing and regulatory roles of the BlsA photoreceptor protein in cells cultured at temperatures below 30°C. This report presents evidence that a light stimulon is operational at 37°C, a condition at which the BlsA production and activity are drastically impaired. Global transcriptional analysis showed that the 37°C light stimulon includes the differential expression of chromosomal genes encoding a wide range of functions that are known to be involved in the adaptation to different metabolic conditions, as well as virulence and persistence in the host and the medical environment. Unexpectedly, the 37°C light stimulon also includes the differential expression of conjugation functions encoded by pAB3 plasmid genes. Our work further demonstrates that the TetR1 and H-NS regulators encoded by this conjugative plasmid control the expression of H2O2 resistance and surface motility, respectively. Furthermore, our data showed that pAB3 has an overall negative effect on the expression of these phenotypes and plays no significant virulence role. Although the nature of the bacterial factors and the mechanisms by which the regulation is attained at 37°C remain unknown, taken together, our work expands the current knowledge about light sensing and gene regulation in A. baumannii. IMPORTANCE As a facultative pathogen, Acinetobacter baumannii persists in various environments by sensing different environmental cues, including light. This report provides evidence of light-dependent regulation at 37°C of the expression of genes coding for a wide range of functions, including those involved in the conjugation of the pAB3 plasmid. Although this plasmid affects the expression of virulence traits when tested under laboratory conditions, it does not have a significant impact when tested using ex vivo and in vivo experimental models. These findings provide a better understanding of the interplay between light regulation and plasmid persistence in the pathobiology of A. baumannii.

Dataset Information

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Publications

Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes.

Similar Datasets

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