The Chlamydia trachomatis Early Effector Tarp Outcompetes Fascin in Forming F-Actin Bundles In Vivo

Aranjuez, George F.; Kim, Jongeon; Jewett, Travis J.

doi:10.3389/fcimb.2022.811407

Cited by 2 publications

References 38 publications

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The N-terminus of theChlamydia trachomatiseffector Tarp engages the host Hippo pathway

Aranjuez,

Patel,

Patel

et al. 2024

Preprint

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Chlamydia trachomatis is an obligate, intracellular Gram-negative bacteria and the leading bacterial STI in the United States. Chlamydia’s developmental cycle involves host cell entry, replication within a parasitophorous vacuole called an inclusion, and induction of host cell lysis to release new infectious particles. During development, Chlamydia manipulates the host cell biology using various secreted bacterial effectors. The early effector Tarp is important for Chlamydia entry via its well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of Tarp’s N-terminus (N-Tarp), though this N-terminal region is present in many Chlamydia species. To address this, we use Drosophila melanogaster as an in vivo cell biology platform to study N-Tarp-host interactions. Drosophila development is well-characterized such that developmental phenotypes can be traced back to the perturbed molecular pathway. Transgenic expression of N-Tarp in Drosophila tissues results in phenotypes consistent with altered host Hippo signaling. The Salvador-Warts-Hippo pathway is a conserved signaling cascade that regulates host cell proliferation and survival during normal animal development. We studied N-Tarp function in larval imaginal wing discs, which are sensitive to perturbations in Hippo signaling. N-Tarp causes wing disc overgrowth and a concomitant increase in adult wing size, phenocopying overexpression of the Hippo co-activator Yorkie. N-Tarp also causes upregulation of Hippo target genes. Last, N-Tarp-induced phenotypes can be rescued by reducing the levels of Yorkie, or the Hippo target genes CycE and Diap1. Thus, we provide the first evidence that the N-terminal region of the Chlamydia effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie. Chlamydia alters host cell apoptosis during infection, though the exact mechanism remains unknown. Our findings implicate the N-terminal region of Tarp as a way to manipulate the host Hippo signaling pathway, which directly influences cell survival.

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The N-terminus of theChlamydia trachomatiseffector Tarp engages the host Hippo pathway

Aranjuez,

Patel,

Patel

et al. 2024

Preprint

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Amoebae as training grounds for microbial pathogens

Price,

Hanford,

Al-Quadan

et al. 2024

mBio

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Grazing of amoebae on microorganisms represents one of the oldest predator-prey dynamic relationships in nature. It represents a genetic “melting pot” for an ancient and continuous multi-directional inter- and intra-kingdom horizontal gene transfer between amoebae and its preys, intracellular microbial residents, endosymbionts, and giant viruses, which has shaped the evolution, selection, and adaptation of microbes that evade degradation by predatory amoeba. Unicellular phagocytic amoebae are thought to be the ancient ancestors of macrophages with highly conserved eukaryotic processes. Selection and evolution of microbes within amoeba through their evolution to target highly conserved eukaryotic processes have facilitated the expansion of their host range to mammals, causing various infectious diseases. Legionella and environmental Chlamydia harbor an immense number of eukaryotic-like proteins that are involved in ubiquitin-related processes or are tandem repeats-containing proteins involved in protein-protein and protein-chromatin interactions. Some of these eukaryotic-like proteins exhibit novel domain architecture and novel enzymatic functions absent in mammalian cells, such as ubiquitin ligases, likely acquired from amoebae. Mammalian cells and amoebae may respond similarly to microbial factors that target highly conserved eukaryotic processes, but mammalian cells may undergo an accidental response to amoeba-adapted microbial factors. We discuss specific examples of microbes that have evolved to evade amoeba predation, including the bacterial pathogens— Legionella , Chlamydia , Coxiella, Rickettssia, Francisella, Mycobacteria , Salmonella, Bartonella , Rhodococcus , Pseudomonas, Vibrio , Helicobacter , Campylobacter , and Aliarcobacter . We also discuss the fungi Cryptococcus, and Asperigillus , as well as amoebae mimiviruses/giant viruses. We propose that amoeba-microbe interactions will continue to be a major “training ground” for the evolution, selection, adaptation, and emergence of microbial pathogens equipped with unique pathogenic tools to infect mammalian hosts. However, our progress will continue to be highly dependent on additional genomic, biochemical, and cellular data of unicellular eukaryotes.

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The Chlamydia trachomatis Early Effector Tarp Outcompetes Fascin in Forming F-Actin Bundles In Vivo

Cited by 2 publications

References 38 publications

The N-terminus of theChlamydia trachomatiseffector Tarp engages the host Hippo pathway

The N-terminus of theChlamydia trachomatiseffector Tarp engages the host Hippo pathway

Amoebae as training grounds for microbial pathogens

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