Hc1‐mediated effects on DNA structure: a potential regulator of chlamydial development

Barry, Clifton E.; Brickman, Timothy J.; Hackstadt, Ted

doi:10.1111/j.1365-2958.1993.tb01689.x

Cited by 69 publications

(102 citation statements)

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“…A total of 26 late genes were identified (Table 1) by microarray. Among these were genes that have been previously characterized as being expressed late in the growth cycle such as hctA and hctB that encode for the chlamydial histone-like proteins and mediate chromosomal condensation in the differentiation of RBs to EBs (24,25). An important aspect of the secondary differentiation process (RB to infectious EB) is the expression of genes that encode proteins that form the highly disulfide cross-linked bacterial OM complex (26).…”

Section: Resultsmentioning

confidence: 99%

“…The RB OM lacks the highly cross-linked OM structure, the chromosome is relaxed and transcriptionally active, and the bacterium multiples by binary fission for a period of 24-36 h. After multiple rounds of replication the RB undergoes a secondary differentiation process back to an infectious EB. Expression of several late genes hctA, hctB, and ompB, ompC; that encode the histone-like proteins (24,25), and the 60 and 12 kDa OM cysteine rich proteins (26), respectively, is associated with differentiation from RB to EB. At this late stage in development (40-60 h) the host cell lyses and releases mature EBs that then reinfect neighboring host cells.…”

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confidence: 99%

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Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis

Belland

Zhong

Crane

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

449

544

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Chlamydia trachomatis is one of the most common bacterial pathogens and is the etiological agent of debilitating sexually transmitted and ocular diseases in humans. The organism is an obligate intracellular prokaryote characterized by a highly specialized biphasic developmental cycle. We have performed genomic transcriptional analysis of the chlamydial developmental cycle. This approach has led to the identification of a small subset of genes that control the primary (immediate-early genes) and secondary (late genes) differentiation stages of the cycle. Immediate-early gene products initiate bacterial metabolism and potentially modify the bacterial phagosome to escape fusion with lysosomes. One immediate early gene (CT147) is a homolog of the human early endosomal antigen-1 that is localized to the chlamydial phagosome; suggesting a functional role for CT147 in establishing the parasitophorous vacuole in a nonfusogenic pathway. Late gene products terminate bacterial cell division and constitute structural components and remodeling activities involved in the formation of the highly disulfide cross-linked outer-membrane complex that functions in attachment and invasion of new host cells. Many of the genes expressed during the immediate-early and late differentiation stages are Chlamydia-specific and have evolutionary origins in eukaryotic lineages.T he Chlamydia trachomatis bacterium is an obligate intracellular pathogen of humans that primarily infects columnar epithelial cells of the ocular and genital mucosae. Chlamydial infections of the eye and genital tract have a significant impact on human health worldwide, causing trachoma, the leading cause of preventable blindness, and sexually transmitted diseases (STD) that include pelvic inflammatory disease and tubal factor infertility (1, 2). Chlamydial STDs are also risk factors in cervical squamous cell carcinoma (3) and HIV infection (4, 5).C. trachomatis has a small genome of Ϸ1 Mb encoding 893 chromosomal and 8 plasmid ORFs that share significant homology in both gene structure and order among strains that infect human and animal hosts (6, 7). Two distinguishing characteristics of this pathogen are its developmental cycle and predilection for causing persistent infections (8). The developmental cycle consists of infectious and noninfectious stages that exhibit unique morphological, biochemical, and biological properties. The infectious elementary body (EB) is a metabolically inactive particle with a rigid, disulfide cross-linked outer membrane (OM) (9-12) that enables the EB to attach to and enter host cells (13-15). After host cell entry, the EB is localized to a phagosome, and the primary differentiation process is initiated. This developmental process involves the commencement of bacterial metabolism and the conversion of the EB to the intracellular replicating form of the organism, termed the reticulate body (RB).At the very early stage of infection (1-3 h) the parasite exerts profound effects on the host. Through an unknown mechanism, dependent on both ba...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis

Belland

Zhong

Crane

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

449

544

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“…Expression of Hc1 in E. coli results in condensation of the chromatin to form a nucleoid structure morphologically indistinguishable from that of EBs (10,12). Concurrent with this phenomenon is a global downregulation of transcription and translation as the chromatin is occluded in the nucleoid complex (10), an effect believed to reflect events in the terminal differentiation of RBs to EBs.…”

Section: Selection Of Chlamydial Genes Required For Nucleoid Decondenmentioning

confidence: 99%

“…Hc1 expression in particular results in a nucleoid ultrastructurally similar to the condensed nucleoid of EBs. Expression levels of Hc1 that result in nucleoid condensation are accompanied by a global downshift in transcription and translation, a phenomenon that also ref lects events during differentiation of RBs to EBs (11,12). Although Hc1 interactions with DNA have been studied extensively both in vivo and in vitro (10 -15), the mechanisms of release of chlamydial chromatin from the constraints imposed by Hc1 association are unknown and have not been studied in chlamydiae.…”

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Chlamydial histone-DNA interactions are disrupted by a metabolite in the methylerythritol phosphate pathway of isoprenoid biosynthesis

Grieshaber

Fischer

Mead

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The chlamydial developmental cycle is characterized by an intracellular replicative form, termed the reticulate body, and an extracellular form called the elementary body. Elementary bodies are characterized by a condensed chromatin, which is maintained by a histone H1-like protein, Hc1. Differentiation of elementary bodies to reticulate bodies is accompanied by dispersal of the chromatin as chlamydiae become transcriptionally active, although the mechanisms of Hc1 release from DNA have remained unknown. Dissociation of the nucleoid requires chlamydial transcription and translation with negligible loss of Hc1. A genetic screen was therefore designed to identify chlamydial genes rescuing Escherichia coli from the lethal effects of Hc1 overexpression. CT804, a gene homologous to ispE, which encodes an intermediate enzyme of the non-mevalonate methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, was selected. E. coli coexpressing CT804 and Hc1 grew normally, although they expressed Hc1 to a level equivalent to that which condensed the chromatin of parent Hc1-expressing controls. Inhibition of the MEP pathway with fosmidomycin abolished IspE rescue of Hc1-expressing E. coli. Deproteinated extract from IspE-expressing bacteria caused dispersal of purified chlamydial nucleoids, suggesting that chlamydial histone-DNA interactions are disrupted by a small metabolite within the MEP pathway rather than by direct action of IspE. By partial reconstruction of the MEP pathway, we determined that 2-C-methylerythritol 2,4-cyclodiphosphate dissociated Hc1 from chlamydial chromatin. These results suggest that chlamydial histone-DNA interactions are disrupted upon germination by a small metabolite in the MEP pathway of isoprenoid biosynthesis.C hlamydia trachomatis is the leading cause of preventable blindness worldwide and a major cause of sexually transmitted disease in developed countries (1). Chlamydiae are bacterial obligate intracellular pathogens with a biphasic developmental cycle that alternates between infectious extracellular forms, termed elementary bodies (EBs), and intracellular replicative forms known as reticulate bodies (RBs) (2). The metabolically inert EBs are characterized by a condensed nucleoid structure. Within a few hours after infection the chromatin becomes dispersed as transcription is initiated and differentiation to the larger, metabolically active RBs begins (3). RBs replicate by binary fission until 18 to 48 h after infection, at which time they begin to differentiate back to EBs, a process typified by recompaction of the nucleoid.The DNA of EBs is held in a condensed state by the action of two histone H1 homologs, Hc1 and Hc2 (4-8). Hc1 is conserved among all chlamydiae, whereas Hc2 displays a variable molecular weight depending on the C. trachomatis serovar and is absent from some chlamydial species and strains (5). Both hctA and hctB, encoding Hc1 and Hc2, respectively, are transcribed late in the developmental cycle concomitant with RB differentiation back to EBs and nucleoid cond...

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Phyla Related to Planctomycetes: Members of Phylum Chlamydiae and Their Implications for Planctomycetes Cell Biology

Bertelli

Greub

2013

Planctomycetes: Cell Structure, Origins and Biology

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Hc1‐mediated effects on DNA structure: a potential regulator of chlamydial development

Cited by 69 publications

References 57 publications

Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis

Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis

Chlamydial histone-DNA interactions are disrupted by a metabolite in the methylerythritol phosphate pathway of isoprenoid biosynthesis

Phyla Related to Planctomycetes: Members of Phylum Chlamydiae and Their Implications for Planctomycetes Cell Biology

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