Altering the redox status of directly impacts its developmental cycle progression.

is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown.

Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions.

is an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle, modifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM, manipulates the host cell to acquire lipids and nutrients necessary for its growth.

The SWIB domain-containing DNA topoisomerase I of mediates DNA relaxation.

The obligate intracellular bacterial pathogen, (Ct), has a distinct DNA topoisomerase I (TopA) with a C-terminal domain (CTD) homologous to eukaryotic SWIB domains. Despite the lack of sequence similarity at the CTDs between TopA (CtTopA) and TopA (EcTopA), full-length CtTopA removed negative DNA supercoils and complemented the growth defect of an mutant. We demonstrated that CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies.

Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions.

is an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle, modifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM, manipulates the host cell to acquire lipids and nutrients necessary for its growth.

Overexpressing the ClpC AAA+ unfoldase accelerates developmental cycle progression in .

is an obligate intracellular bacterium that undergoes a complex biphasic developmental cycle, alternating between the smaller, infectious, non-dividing elementary body (EB) and the larger, non-infectious but dividing reticulate body. Due to the differences between these functionally and morphologically distinct forms, we hypothesize protein degradation is essential to chlamydial differentiation. The bacterial Clp system, consisting of an ATPase unfoldase (e.

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

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. 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).

Altering the redox status of directly impacts its developmental cycle progression.

is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: elementary body (EB) and reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown.

Inc Ct226 is vital for FLI1 and LRRF1 recruitment to the chlamydial inclusion.

The obligate intracellular pathogen, , establishes an intracellular niche within a host membrane-derived vacuole called the chlamydial inclusion. From within this inclusion, orchestrates numerous host-pathogen interactions, in part, by utilizing a family of type III secreted effectors, termed inclusion membrane proteins (Incs). Incs are embedded within the inclusion membrane, and some function to recruit host proteins to the inclusion.

Metabolic model guided CRISPRi identifies a central role for phosphoglycerate mutase in persistence.

Unlabelled: Upon nutrient starvation, serovar L2 (CTL) shifts from its normal growth to a non-replicating form, termed persistence. It is unclear if persistence reflects an adaptive response or a lack thereof. To understand this, transcriptomics data were collected for CTL grown under nutrient-replete and nutrient-starved conditions.

Cyclic di-AMP drives developmental cycle progression in .

The obligate intracellular bacterium alternates between two functional forms during its developmental cycle: elementary body (EB) and reticulate body (RB). However, the molecular mechanisms governing the transitions between these forms are unknown. Here, we present evidence cyclic di-AMP (c-di-AMP) is a key factor in triggering the transition from RB to EB (i.

Targeted repression of by CRISPRi reveals a critical function for balanced DNA topoisomerase I activity in the developmental cycle.

is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling developmental processes.

Protein-Protein Interaction: Bacterial Two Hybrid.

The bacterial two-hybrid (BACTH, for "Bacterial Adenylate Cyclase-based Two-Hybrid") system is a simple and fast genetic approach to detect and characterize protein-protein interactions in vivo. This system is based on the interaction-mediated reconstitution of a cAMP signaling cascade in Escherichia coli. As BACTH uses a diffusible cAMP messenger molecule, the physical association between the two interacting chimeric proteins can be spatially separated from the transcription activation readout, and therefore, it is possible to analyze protein-protein interactions that occur either in the cytosol or at the inner membrane level as well as those that involve DNA-binding proteins.

Identification of the alternative sigma factor regulons of using multiplexed CRISPR interference.

is a developmentally regulated, obligate intracellular bacterium that encodes three sigma factors: σ66, σ54, and σ28. σ66 is the major sigma factor controlling most transcription initiation during early- and mid-cycle development as the infectious elementary body (EB) transitions to the non-infectious reticulate body (RB) that replicates within an inclusion inside the cell. The roles of the minor sigma factors, σ54 and σ28, have not been well characterized to date; however, there are data to suggest each functions in late-stage development and secondary differentiation as RBs transition to EBs.

Persistence of obligate intracellular pathogens: alternative strategies to overcome host-specific stresses.

In adapting to the intracellular niche, obligate intracellular bacteria usually undergo a reduction of genome size by eliminating genes not needed for intracellular survival. These losses can include, for example, genes involved in nutrient anabolic pathways or in stress response. Living inside a host cell offers a stable environment where intracellular bacteria can limit their exposure to extracellular effectors of the immune system and modulate or outright inhibit intracellular defense mechanisms.

The Unique N-Terminal Domain of Chlamydial Bactofilin Mediates Its Membrane Localization and Ring-Forming Properties.

Chlamydia trachomatis is an obligate intracellular bacterial pathogen. In evolving to the intracellular niche, Chlamydia has reduced its genome size compared to other bacteria and, as a consequence, has a number of unique features. For example, Chlamydia engages the actin-like protein MreB, rather than the tubulin-like protein FtsZ, to direct peptidoglycan (PG) synthesis exclusively at the septum of cells undergoing polarized cell division.

Identification of the alternative sigma factor regulons of using multiplexed CRISPR interference.

Unlabelled: is a developmentally regulated, obligate intracellular bacterium that encodes three sigma factors: σ66, σ54, and σ28. σ66 is the major sigma factor controlling most transcription initiation during early and mid-cycle development as the infectious EB transitions to the non-infectious RB that replicates within an inclusion inside the cell. The roles of the minor sigma factors, σ54 and σ28, have not been well characterized to date - however, there are data to suggest each functions in late-stage development and secondary differentiation as RBs transition to EBs.

The Periplasmic Tail-Specific Protease, Tsp, Is Essential for Secondary Differentiation in .

The obligate intracellular human pathogen Chlamydia trachomatis (Ctr) undergoes a complex developmental cycle in which the bacterium differentiates between two functionally and morphologically distinct forms: the elementary body (EB) and the reticulate body (RB). The EB is the smaller, infectious, nondividing form which initiates infection of a susceptible host cell, whereas the RB is the larger, non-infectious form which replicates within a membrane-bound vesicle called an inclusion. The mechanism(s) which drives differentiation between these developmental forms is poorly understood.

Targeted repression of DNA topoisomerase I by CRISPRi reveals a critical function for it in the developmental cycle.

is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infections. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases (Topos) contributes to developmental processes.

Molecular Characterization of the ClpC AAA+ ATPase in the Biology of Chlamydia trachomatis.

Bacterial AAA+ unfoldases are crucial for bacterial physiology by recognizing specific substrates and, typically, unfolding them for degradation by a proteolytic component. The aseinoytic rotease (Clp) system is one example where a hexameric unfoldase (e.g.

An NlpC/P60 protein catalyzes a key step in peptidoglycan recycling at the intersection of energy recovery, cell division and immune evasion in the intracellular pathogen Chlamydia trachomatis.

The obligate intracellular Chlamydiaceae do not need to resist osmotic challenges and thus lost their cell wall in the course of evolution. Nevertheless, these pathogens maintain a rudimentary peptidoglycan machinery for cell division. They build a transient peptidoglycan ring, which is remodeled during the process of cell division and degraded afterwards.

Design, Biological Evaluation, and Computer-Aided Analysis of Dihydrothiazepines as Selective Antichlamydial Agents.

(CT) causes the most prevalent sexually transmitted bacterial disease in the United States. The lack of drug selectivity is one of the main challenges of the current antichlamydial pharmacotherapy. The metabolic needs of CT are controlled, among others, by cylindrical proteases and their chaperones (, ClpX).

Tryptophan Availability during Persistence of Chlamydia trachomatis Directly Impacts Expression of Chlamydial Cell Division Proteins.

Chlamydia is an obligate intracellular pathogen with a highly reduced genome devoid of major stress response genes like and , which mediate the stringent response. Interestingly, as an intracellular bacterium dependent on its host for nutrients and as a tryptophan (Trp) auxotroph, Chlamydia is very sensitive to Trp starvation, which is induced by the host cytokine interferon-γ. In response to Trp starvation, Chlamydia enters a viable but nonreplicating state called persistence.