The Repressor Function of the Chlamydia Late Regulator EUO Is Enhanced by the Plasmid-Encoded Protein Pgp4

• Published in: Journal of bacteriology 2020-03, Vol.202 (8)
• Main Authors: Zhang, Qiang, Rosario, Christopher J, Sheehan, Lauren M, Rizvi, Syed M, Brothwell, Julie A, He, Cheng, Tan, Ming
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Chlamydia; Chlamydia Infections - microbiology; Chlamydia trachomatis - genetics; Chlamydia trachomatis - metabolism; Conversion; Gene expression; Gene Expression Regulation, Bacterial; Genes; Humans; Immunofluorescence; Plasmids - genetics; Plasmids - metabolism; Progeny; Promoter Regions, Genetic; Promoters; Proteins; Replication; Repressor Proteins - genetics; Repressor Proteins - metabolism; Research Article; Sexually transmitted diseases; Spotlight; STD; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.00793-19

A critical step in intracellular infection is the production of infectious progeny through the expression of late genes. This differentiation step involves conversion from a reticulate body (RB), which is the replicating form of the bacterium, into an elementary body (EB), which is the developmental form that spreads the infection to a new host cell. EUO is an important chlamydial transcription factor that controls the expression of late genes, but the mechanisms that regulate EUO are not known. We report that a plasmid-encoded protein, Pgp4, enhanced the repressor activity of EUO. Pgp4 did not function as a transcription factor because it did not bind or directly modulate transcription of its target promoters. Instead, Pgp4 increased the ability of EUO to bind and repress EUO-regulated promoters and physically interacted with EUO in pulldown assays with recombinant proteins. We detected earlier onset of EUO-dependent late gene expression by immunofluorescence microscopy in Pgp4-deficient and strains. In addition, the absence of Pgp4 led to earlier onset of RB-to-EB conversion in These data support a role for Pgp4 as a negative regulator of chlamydial transcription that delays late gene expression. Our studies revealed that Pgp4 also has an EUO-independent function as a positive regulator of chlamydial transcription. is an important human pathogen that causes more than 150 million active cases of genital and eye infection in the world. This obligate intracellular bacterium produces infectious progeny within an infected human cell through the expression of late chlamydial genes. We showed that the ability of a key chlamydial transcription factor, EUO, to repress late genes was enhanced by a plasmid-encoded protein, Pgp4. In addition, studies with Pgp4-deficient strains provide evidence that Pgp4 delays late gene expression in infected cells. Thus, Pgp4 is a novel regulator of late gene expression in through its ability to enhance the repressor function of EUO.