Intracellular lifestyle of Chlamydia trachomatis and host–pathogen interactions

Stelzner, Kathrin; Vollmuth, Nadine; Rudel, Thomas

doi:10.1038/s41579-023-00860-y

Cited by 15 publications

(11 citation statements)

References 188 publications

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“…At one end of the scale, with only 1.2% of its genome dedicated to cooperation is Buchnera aphidicola, a symbiont that lives inside aphids (74). At the other end of the scale, with 5.3% its genome dedicated to cooperation is Chlamydia trachomatis , an obligate intracellular pathogen (75). Both species have tiny genomes (<1000 proteins), but very different lifestyles.…”

Section: Resultsmentioning

confidence: 99%

SOCfinder: a genomic tool for identifying cooperative genes in bacteria

Belcher,

Dewar,

Hao

et al. 2023

Preprint

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Bacteria cooperate by working collaboratively to defend their colonies, share nutrients, and resist antibiotics. Nevertheless, our understanding of these remarkable behaviours primarily comes from studying a few well-characterized species. Consequently, there is a significant gap in our understanding of microbial cooperation, particularly in natural environments. To address this gap, we can use bioinformatic tools to identify cooperative traits and their underlying genes across diverse species. Existing tools address this challenge through two approaches. One approach is to identify genes that encode extracellular proteins, which can provide benefits to neighbouring cells. An alternative approach is to predict gene function using annotation tools. However, these tools have several limitations. Not all extracellular proteins are cooperative, and not all cooperative behaviours are controlled by extracellular proteins. Furthermore, existing functional annotation methods frequently miss known cooperative genes. Here, we introduce SOCfinder as a new tool to find cooperative genes in bacterial genomes. SOCfinder combines information from several methods, considering if a gene is likely to (1) code for an extracellular protein, (2) have a cooperative functional annotation, or (3) be part of the biosynthesis of a cooperative secondary metabolite. We use data on two extensively-studied species (P. aeruginosa & B. subtilis) to show that SOCfinder is better at finding known cooperative genes than existing tools. We also use theory from population genetics to identify a signature of kin selection in SOCfinder cooperative genes, which is lacking in genes identified by existing tools. SOCfinder opens up a number of exciting directions for future research, and is available to download from https://github.com/lauriebelch/SOCfinder.

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Section: Resultsmentioning

confidence: 99%

SOCfinder: a genomic tool for identifying cooperative genes in bacteria

Belcher,

Dewar,

Hao

et al. 2023

Preprint

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“…C. trachomatis exhibited a closed pangenome ( α = 0.97), indicating a limited capacity for gene acquisition through HGT. This suggests a relatively stable genome and a more specialized lifestyle, features associated with an obligate intracellular pathogenic behavior 39 . This pattern is frequent among species with high genomic discontinuity, closed pangenomes, allopatric lifestyles, and highly conserved pangenomes (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Relating Ecological Diversity to Genetic Discontinuity across Bacterial Species

Passarelli-Araujo,

Venancio,

Hanage

2023

Preprint

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Bacterial genetic discontinuity, representing abrupt breaks in genomic identity among species, is crucial for grasping microbial diversity and evolution. Advances in genomic sequencing have enhanced our ability to track and characterize genetic discontinuity in bacterial populations. However, exploring systematically the degree to which bacterial diversity exists as a continuum or is sorted into discrete and readily defined species remains a challenge in microbial ecology. Here, we aimed to quantify the genetic discontinuity (δ) and investigate how this metric is related to ecology. We harnessed a dataset comprising 210,129 genomes to systematically explore genetic discontinuity patterns across several distantly related species, finding clear breakpoints which varied depending on the taxa in question. By delving into pangenome characteristics, we uncovered a significant association between pangenome saturation and genetic discontinuity. Closed pangenomes were associated with more pronounced breaks, exemplified byMycobacterium tuberculosis. Additionally, through a machine learning approach, we detected key features that impact genetic discontinuity prediction. Our study enhances the understanding of bacterial genetic patterns and their ecological implications, offering insights into species boundaries for prokaryotes.

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“…As a successful intracellular pathogen, Chlamydia must replicate intracellularly while avoiding immune detection(3, 12, 32). Although C. trachomatis induces cell-autonomous signaling pathways, including the cGAS-STING, NF-kB, and JNK-AP-1 pathways, it must modulate their downstream effects to survive intracellularly(3, 12, 33). C. trachomatis is thought to regulate some of these pathways through the secretion of soluble effectors, including Incs(3, 11, 12).…”

Section: Discussionmentioning

confidence: 99%

“…The roles of most Chlamydia secreted effectors, including the Incs, remain incompletely described (8), as bioinformatics has been unrevealing and conventional genetic manipulation of Chlamydia species has only recently been achieved (9). Based on their topology and on functional studies, Incs may function as scaffolds to recruit and/or subvert host cell proteins or organelles (3,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

TheChlamydia trachomatisInc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners

Herrera,

McMahon,

Swaney

et al. 2024

Preprint

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Chlamydia trachomatisis the leading cause of bacterial sexually transmitted infections in the US and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood.C. trachomatisaccomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, theinclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated withC. trachomatisinfection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen activated protein kinase kinase kinase 2 (MEKK2) and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling duringC. trachomatisinfection.ImportanceChlamydia trachomatisis the leading cause of bacterial sexually transmitted infections in the US and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between aC. trachomatissecreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrate that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis ofC. trachomatisinfections, but also in understanding the role of TRAF7 in cancer.

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Intracellular lifestyle of Chlamydia trachomatis and host–pathogen interactions

Cited by 15 publications

References 188 publications

SOCfinder: a genomic tool for identifying cooperative genes in bacteria

SOCfinder: a genomic tool for identifying cooperative genes in bacteria

Relating Ecological Diversity to Genetic Discontinuity across Bacterial Species

TheChlamydia trachomatisInc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners

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