DksA-dependent regulation of RpoS contributes to Borrelia burgdorferi tick-borne transmission and mammalian infectivity.

Autor: Boyle WK; Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, United States of America., Richards CL; Laboratory of Bacteriology, Gene Regulation Section, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America., Dulebohn DP; Laboratory of Bacteriology, Gene Regulation Section, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America., Zalud AK; Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, United States of America., Shaw JA; Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, United States of America., Lovas S; Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, United States of America., Gherardini FC; Laboratory of Bacteriology, Gene Regulation Section, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America., Bourret TJ; Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Feb 18; Vol. 17 (2), pp. e1009072. Date of Electronic Publication: 2021 Feb 18 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009072
Abstrakt: Throughout its enzootic cycle, the Lyme disease spirochete Borreliella (Borrelia) burgdorferi, senses and responds to changes in its environment using a small repertoire of transcription factors that coordinate the expression of genes required for infection of Ixodes ticks and various mammalian hosts. Among these transcription factors, the DnaK suppressor protein (DksA) plays a pivotal role in regulating gene expression in B. burgdorferi during periods of nutrient limitation and is required for mammalian infectivity. In many pathogenic bacteria, the gene regulatory activity of DksA, along with the alarmone guanosine penta- and tetra-phosphate ((p)ppGpp), coordinate the stringent response to various environmental stresses, including nutrient limitation. In this study, we sought to characterize the role of DksA in regulating the transcriptional activity of RNA polymerase and its role in the regulation of RpoS-dependent gene expression required for B. burgdorferi infectivity. Using in vitro transcription assays, we observed recombinant DksA inhibits RpoD-dependent transcription by B. burgdorferi RNA polymerase independent of ppGpp. Additionally, we determined the pH-inducible expression of RpoS-dependent genes relies on DksA, but this relationship is independent of (p)ppGpp produced by Relbbu. Subsequent transcriptomic and western blot assays indicate DksA regulates the expression of BBD18, a protein previously implicated in the post-transcriptional regulation of RpoS. Moreover, we observed DksA was required for infection of mice following intraperitoneal inoculation or for transmission of B. burgdorferi by Ixodes scapularis nymphs. Together, these data suggest DksA plays a central role in coordinating transcriptional responses in B. burgdorferi required for infectivity through DksA's interactions with RNA polymerase and post-transcriptional control of RpoS.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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