Distinct impacts of each anti-anti-sigma factor ortholog of the chlamydial Rsb partner switching mechanism on development in Chlamydia trachomatis

Shiomi Junker, Vandana Singh, Aamal G.M. Al-Saadi, Nicholas A. Wood, Scott D. Hamilton-Brehm, Scot P. Ouellette, Derek J. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

Partner switching mechanisms (PSMs) are signal transduction systems comprised of a sensor phosphatase (RsbU), an anti-sigma factor (RsbW, kinase), an anti-anti-sigma factor (RsbV, the RsbW substrate), and a target sigma factor. Chlamydia spp. are obligate intracellular bacterial pathogens of animals that undergo a developmental cycle transitioning between the infectious elementary body (EB) and replicative reticulate body (RB) within a host cell-derived vacuole (inclusion). Secondary differentiation events (RB to EB) are transcriptionally regulated, in part, by the housekeeping sigma factor (σ66) and two late-gene sigma factors (σ54 and σ28). Prior research supports that the PSM in Chlamydia trachomatis regulates availability of σ66. Pan-genome analysis revealed that PSM components are conserved across the phylum Chlamydiota, with Chlamydia spp. possessing an atypical arrangement of two anti-anti-sigma factors, RsbV1 and RsbV2. Bioinformatic analyses support RsbV2 as the homolog to the pan-genome-conserved RsbV with RsbV1 as an outlier. This, combined with in vitro data, indicates that RsbV1 and RsbV2 are structurally and biochemically distinct. Reduced levels or overexpression of RsbV1/RsbV2 did not significantly impact C. trachomatis growth or development. In contrast, overexpression of a non-phosphorylatable RsbV2 S55A mutant, but not overexpression of an RsbV1 S56A mutant, resulted in a 3 log reduction in infectious EB production without reduction in genomic DNA (total bacteria) or inclusion size, suggesting a block in secondary differentiation. The block was corroborated by reduced production of σ54/28-regulated late proteins and via transmission electron microscopy.

Original languageEnglish (US)
JournalMicrobiology Spectrum
Volume12
Issue number12
DOIs
StatePublished - Dec 2024

Keywords

  • anti-anti-sigma factor
  • Chlamydia
  • development
  • phosphorylation
  • RsbV

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases

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