Division without Binary Fission: Cell Division in the FtsZ-Less
            <i>Chlamydia</i>

Ouellette, Scot P.; Lee, Junghoon; Cox, John V.

doi:10.1128/jb.00252-20

Cited by 32 publications

(25 citation statements)

References 61 publications

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“…This is also supported by other studies that have provided evidence for asymmetric cell division in C. trachomatis . These studies show that the cell division machinery assembles asymmetrically, leading to polarized RB division ( 43 , 51 , 52 ). Additionally, the EB itself is asymmetric, demonstrating hemispherical projections that can be seen by electron microscopy ( 53 ).…”

Section: Discussionmentioning

confidence: 95%

Single-Inclusion Kinetics of Chlamydia trachomatis Development

et al. 2020

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The obligate intracellular bacterial pathogen Chlamydia trachomatis is reliant on a developmental cycle consisting of two cell forms, termed the elementary body (EB) and the reticulate body (RB). The EB is infectious and utilizes a type III secretion system and preformed effector proteins during invasion, but it does not replicate. The RB replicates in the host cell but is noninfectious. This developmental cycle is central to chlamydial pathogenesis. In this study, we developed mathematical models of the developmental cycle that account for potential factors influencing RB-to-EB cell type switching during infection. Our models predicted that two categories of regulatory signals for RB-to-EB development could be differentiated experimentally, an “intrinsic” cell-autonomous program inherent to each RB and an “extrinsic” environmental signal to which RBs respond. To experimentally differentiate between mechanisms, we tracked the expression of C. trachomatis development-specific promoters in individual inclusions using fluorescent reporters and live-cell imaging. These experiments indicated that EB production was not influenced by increased multiplicity of infection or by superinfection, suggesting the cycle follows an intrinsic program that is not directly controlled by environmental factors. Additionally, live-cell imaging revealed that EB development is a multistep process linked to RB growth rate and cell division. The formation of EBs followed a progression with expression from the euo and ihtA promoters evident in RBs, while expression from the promoter for hctA was apparent in early EBs/IBs. Finally, expression from the promoters for the true late genes, hctB, scc2, and tarp, was evident in the maturing EB. IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that can cause trachoma, cervicitis, urethritis, salpingitis, and pelvic inflammatory disease. To establish infection in host cells, Chlamydia must complete a multiple-cell-type developmental cycle. The developmental cycle consists of specialized cells, the EB cell, which mediates infection of new host cells, and the RB cell, which replicates and eventually produces more EB cells to mediate the next round of infection. By developing and testing mathematical models to discriminate between two competing hypotheses for the nature of the signal controlling RB-to-EB cell type switching, we demonstrate that RB-to-EB development follows a cell-autonomous program that does not respond to environmental cues. Additionally, we show that RB-to-EB development is a function of chlamydial growth and division. This study serves to further our understanding of the chlamydial developmental cycle that is central to the bacterium’s pathogenesis.

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Section: Discussionmentioning

confidence: 95%

Single-Inclusion Kinetics of Chlamydia trachomatis Development

et al. 2020

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“…Finally, we compared the localization pattern of these proteins to MreB_6xH, a characterized division protein in Chlamydia that substitutes for FtsZ [11,14]. Prior to the initiation of division, MreB_6xH, like Cls_6xH, is clustered at a site on the MOMP-enriched side of the mother cell.…”

Section: Resultsmentioning

confidence: 99%

“…Chlamydia is unique amongst characterized bacteria in using an MreB-dependent polarized cell division process [11,16]. Although much recent work has identified the predicted components of the chlamydial divisome [11,12,14,31], it is unclear how a division site is selected given that Chlamydia are coccoid bacteria with apparent uniformity in their negative membrane curvature. An additional issue for Chlamydia is that MreB is typically excluded from areas of negative membrane curvature, thus how it is recruited to the inner leaflet of the inner membrane at a distinct site was unclear prior to this study.…”

Section: Discussionmentioning

confidence: 99%

Localized Cardiolipin Synthesis is Required for the Assembly of MreB During the Polarized Cell Division ofChlamydia trachomatis

Ouellette

Fisher-Marvin

Harpring

et al. 2022

Preprint

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Pathogenic Chlamydia species are coccoid bacteria that use the rod-shape determining protein MreB to direct septal peptidoglycan synthesis during their polarized cell division process. How the site of polarized budding is determined in this bacterium, where contextual features like membrane curvature are seemingly identical, is unclear. We hypothesized that the accumulation of the phospholipid, cardiolipin (CL), in specific regions of the cell membrane induces localized membrane changes that trigger the recruitment of MreB to the site where the bud will arise. To test this, we ectopically expressed cardiolipin synthase (Cls) and observed a polar distribution for this enzyme in Chlamydia trachomatis. In early division intermediates, Cls was restricted to the bud site where MreB is localized and peptidoglycan synthesis is initiated. The localization profile of Cls throughout division mimicked the distribution of lipids that stain with NAO, a dye that labels CL. Treatment of Chlamydia with 3-,6-dinonylneamine (diNN), an antibiotic targeting CL-containing membrane domains, resulted in redistribution of Cls and NAO-staining phospholipids. In addition, MreB localization was altered by diNN treatment, suggesting an upstream regulatory role for CL-containing membranes in directing the assembly of MreB. This hypothesis is consistent with the observation that the clustered localization of Cls is not dependent upon MreB function or peptidoglycan synthesis. Furthermore, expression of a CL-binding protein at the inner membrane of C. trachomatis dramatically inhibited bacterial growth supporting the importance of CL in the division process. Our findings implicate a critical role for localized CL synthesis in driving MreB assembly at the bud site during the polarized cell division of Chlamydia.

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“…While members of the Chlamydiae encode a number of components involved in localized PG synthesis, they lack the central protein responsible for directing the septal division machinery in most other bacterial species; FtsZ ( Ouellette et al, 2020 ). However, these organisms do possess the fundamental elements of the side wall (RodA ( Meeske et al, 2016 ), PBP2) and septal (FtsW ( Taguchi et al, 2019 ), PBP3) PG polymerases.…”

Section: Discussionmentioning

confidence: 99%

Localized Peptidoglycan Biosynthesis in Chlamydia trachomatis Conforms to the Polarized Division and Cell Size Reduction Developmental Models

Liechti

2021

Front. Microbiol.

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Cell size regulation in bacteria is a function of two basic cellular processes: the expansion of the cell envelope and its constriction at spatially defined points at what will eventually become the division plane. In most bacterial species, both cell wall expansion and restriction are dependent on peptidoglycan (PG), a structural polymer comprised of sugars and amino acids that imparts strength and rigidity to bacterial membranes. Pathogenic Chlamydia species are unique in that their cell walls contain very little PG, which is restricted almost entirely to the apparent division plane of the microbe’s replicative forms. Very little is known about the degree to which PG affects the size and shape of C. trachomatis during its division process, and recent studies suggest the process is initiated via a polarized mechanism. We conducted an imaging study to ascertain the dimensions, orientation, and relative density of chlamydial PG throughout the organism’s developmental cycle. Our analysis indicates that PG in replicating C. trachomatis can be associated with four, broad structural forms; polar/septal disks, small/thick rings, large rings, and small/thin rings. We found that PG density appeared to be highest in septal disks and small/thick rings, indicating that these structures likely have high PG synthesis to degradation ratios. We also discovered that as C. trachomatis progresses through its developmental cycle PG structures, on average, decrease in total volume, indicating that the average cell volume of chlamydial RBs likely decreases over time. When cells infected with C. trachomatis are treated with inhibitors of critical components of the microbe’s two distinct PG synthases, we observed drastic differences in the ratio of PG synthesis to degradation, as well as the volume and shape of PG-containing structures. Overall, our results suggest that C. trachomatis PG synthases differentially regulate the expansion and contraction of the PG ring during both the expansion and constriction of the microbe’s cell membrane during cell growth and division, respectively.

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Division without Binary Fission: Cell Division in the FtsZ-Less Chlamydia

Cited by 32 publications

References 61 publications

Single-Inclusion Kinetics of Chlamydia trachomatis Development

Single-Inclusion Kinetics of Chlamydia trachomatis Development

Localized Cardiolipin Synthesis is Required for the Assembly of MreB During the Polarized Cell Division ofChlamydia trachomatis

Localized Peptidoglycan Biosynthesis in Chlamydia trachomatis Conforms to the Polarized Division and Cell Size Reduction Developmental Models

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