Chlamydia Gene Regulation

Rosario, Christopher J.; Soules, Katelyn R.; Hefty, P. Scott; Tan, Ming

doi:10.21775/9781912530281.10

Cited by 8 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We next investigated if H89 causes this disproportionate reduction in infectious chlamydiae by disrupting RB-to-EB conversion. As chlamydial late genes are expressed during RB-to-EB conversion ( 33 ), we monitored the expression of the late gene product OmcB, which is an outer membrane protein only present in EBs ( 34 , 35 ). Immunofluorescence microscopy analysis detected fewer OmcB-positive foci in inclusions of H89-treated cells than in controls at all three time points ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The Small Molecule H89 Inhibits Chlamydia Inclusion Growth and Production of Infectious Progeny

et al. 2021

Self Cite

View full text Add to dashboard Cite

Chlamydia is an obligate intracellular bacterium and the most common reportable cause of human infection in the U.S. This pathogen proliferates inside a eukaryotic host cell, where it resides within a membrane-bound compartment called the chlamydial inclusion. It has an unusual developmental cycle, marked by conversion between a replicating form, the reticulate body (RB), and an infectious form, the elementary body (EB). We found that the small molecule H89 slowed inclusion growth and decreased overall RB replication by 2-fold, but caused a 25-fold reduction in infectious EBs. This disproportionate effect on EB production was mainly due to a defect in RB-to-EB conversion and not to the induction of chlamydial persistence, which is an altered growth state. Although H89 is a known inhibitor of specific protein kinases and vesicular transport to and from the Golgi, it did not cause these anti-chlamydial effects by blocking the protein kinases PKA or PKC, or by inhibiting protein or lipid transport. H89 is thus a novel anti-chlamydial compound that has a unique combination of effects on the intracellular Chlamydia infection.

show abstract

Section: Resultsmentioning

confidence: 99%

The Small Molecule H89 Inhibits Chlamydia Inclusion Growth and Production of Infectious Progeny

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to these mechanisms of gene regulation, Chlamydia may control RNA polymerase activity through an anti-sigma factor that binds and sequesters the sigma factor (Rosario et al, 2020). The sigma factor is the subunit of RNA polymerase that allows it to recognize and bind specific promoter DNA sequences and thereby transcribe its target genes.…”

Section: Introductionmentioning

confidence: 99%

“…Chlamydial genes are transcribed in three temporal waves that correspond to these three developmental stages (Belland et al, 2003; Nicholson et al, 2003; Rosario et al, 2020; Shaw et al, 2000). For example, early genes are transcribed within the first few hours of EB entry into the host cell (Belland et al, 2003; Hayward et al, 2021; Humphrys et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Chlamydia RsbU phosphatase activity by the enolase product, phosphoenolpyruvate

Rosario

Tan

2022

Preprint

Self Cite

View full text Add to dashboard Cite

The intracellular pathogen Chlamydia temporally regulates the expression of its genes but the upstream signals that control transcription are not known. The best studied regulatory pathway is a partner switching mechanism that involves an anti-sigma factor RsbW, which inhibits transcription by binding and sequestering the sigma subunit of RNA polymerase. RsbW is itself regulated by an anti-anti-sigma factor RsbV whose phosyphorylation state is controlled by the phosphatase RsbU. In this study, we showed that Chlamydia trachomatis RsbU requires manganese or magnesium as a cofactor and dephosphorylates RsbV1 and RsbV2, which are the two chlamydial paralogs of RsbV. The gene for RsbU is adjacent to the enolase gene in a number of Chlamydia genomes, and we showed that eno and rsbU are co-transcribed from the same operon. In other bacteria, there is no known functional connection between the Rsb pathway and enolase, which is an enzyme in the glycolytic pathway. We found, however, that Chlamydia RsbU phosphatase activity was inhibited by phosphoenolpyruvate (PEP), the product of the enolase reaction, but not by 2-phosphoglycerate (2PGA), which is the substrate. These findings suggest that the enolase reaction, and more generally glucose metabolism, may provide an upstream signal that regulates transcription in Chlamydia through the RsbW pathway.IMPORTANCEThe RsbW pathway is a phosphorelay that regulates gene expression in Chlamydia but its upsteam signal has not been identified. We showed that RsbU, a phosphatase in this pathway is inhibited by phosphoenolpyruvate, which is the product of the enolase reaction. As enolase is an enzyme in the glycolytic pathway, these results reveal an unrecognized link between glucose metabolism and gene regulation in chlamydiae. Moreover, as these intracellular bacteria acquire gluose from the infected host cell, our findings suggest that glucose availability may be an external signal that controls chlamydial gene expression.

show abstract

“…Early genes play important roles in establishing the inclusion, and midcycle genes are expressed during RB replication. Late genes are expressed during RB-to-EB conversion and include genes with EB-specific functions ( 7 ). For example, hctA and hctB encode histone-like proteins HctA (also known as Hc1) and HctB (or Hc2), which condense the DNA in EBs, while omcB encodes an EB-specific outer membrane protein ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…For example, hctA and hctB encode histone-like proteins HctA (also known as Hc1) and HctB (or Hc2), which condense the DNA in EBs, while omcB encodes an EB-specific outer membrane protein ( 8 , 9 ). Most of the work on chlamydial gene expression has focused on the regulation of transcription by transcription factors and alternative sigma factors ( 7 ). In contrast, little is known about the posttranscriptional regulation of gene expression in Chlamydia .…”

Section: Introductionmentioning

confidence: 99%