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

Infection and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

ABSTRACT Chlamydia is an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called inclusion. Throughout its developmental cycle, modifies the inclusion membrane (IM) with type III secreted (T3S) proteins, known as proteins (Incs). Via IM, manipulates host cell to acquire lipids and nutrients necessary for growth. One key nutrient tryptophan (Trp). As Trp auxotroph, very sensitive starvation and, in response low levels induced by immune response, enters viable but nonreplicating state persistence. To maintain viability during persistence, must necessarily both integrity of IM ability modify responses, how affects composition subsequent interactions remains poorly understood. We hypothesize that, under conditions, Inc expression/stability or T3S function persistence alters host- will be preserved. examine we examined sphingomyelin, cholesterol, transferrin trafficking inclusion, well localization bind specific Incs. identified changes monitoring endogenous abundance at IM. Chlamydial generally functional Specific can linked content effector-specific defects chlamydial T3S. Overall, our findings reveal critical are maintained mediated starvation.

Language: Английский

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Expression activation of over 70% of Chlamydia trachomatis genes during the first hour of infection

Infection and Immunity, Journal Year: 2024, Volume and Issue: 92(3)

Published: Feb. 1, 2024

ABSTRACT The obligate intracellular bacterium Chlamydia has a unique developmental cycle that alternates between two contrasting cell types. With hardy envelope and highly condensed genome, the small elementary body (EB) maintains limited metabolic activities yet survives in extracellular environments is infectious. After entering host cells, EBs differentiate into larger proliferating reticulate bodies (RBs). Progeny are derived from RBs late stages eventually exit cells. How expression of chlamydial genome consisting nearly 1,000 genes governs unclear. A previous microarray study identified only 29 trachomatis immediate early genes, defined as with increased during first hour postinoculation cultured In this study, we performed more sensitive RNA sequencing (RNA-Seq) analysis for C. cultures high multiplicities infection. Remarkably, observed well over 700 C . underwent 2- to 900-fold activation within 1 postinoculation. Quantitative reverse transcription real-time PCR was further used validate activated large subset by RNA-Seq. Importantly, our results demonstrate transcriptome 20 times extensive than previously realized. Gene ontology indicates spans all functional categories. We conclude 70% almost immediately upon entry thus implicating their importance initiating rapid differentiation establishing an niche conducive development growth.

Language: Английский

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PEPSeek-mediated identification of novel epitopes from viral and bacterial pathogens and the impact on host cell immunopeptidomes

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100937 - 100937

Published: March 1, 2025

Here, we develop PEPSeek, a web-server based software to allow higher performance in the identification of pathogen-derived epitope candidates detected via mass spectrometry MHC class I immunopeptidomes. We apply it human and mouse cell lines infected with either SARS-CoV-2, Listeria monocytogenes or Chlamydia trachomatis, thereby identifying large number novel antigens epitopes that prove be recognized by CD8+ T cells. In cells, identified antigenic peptide features suggested how processing presentation pathogenic differ between pathogens. The quantitative tools PEPSeek also helped define C. trachomatis infection cycle could impact on landscape host system, likely reflecting metabolic changes occurred

Language: Английский

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COPB1-knockdown induced type I interferon signaling activation inhibits Chlamydia psittaci intracellular proliferation

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 6, 2025

Chlamydia psittaci is a zoonotic pathogen that causes an acute disease known as psittacosis. To establish infection in host cells, manipulates the cell's membrane trafficking pathways. In this study, using fluorescently labeled C. and screening human small interfering RNA (siRNA) library, we identified 34 proteins influenced HeLa cells. Among these, knockdown (KD) of two genes encoding subunits coatomer complex I (COPI) inhibited pathogen's intracellular survival. Specifically, COPB1, COPI subunit, significantly reduced proliferation psittaci. Mechanistically, found type interferon negatively affected infection. Moreover, COPB1 KD disrupted homeostasis STING, preventing its retrieval from Golgi back to endoplasmic reticulum (ER), which turn activated signaling. Together, our findings advance understanding mechanisms underlying offer potential avenues for development new anti-C. strategies.

Language: Английский

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Chlamydia trachomatis invasion: a duet of effectors

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 00(00)

Published: March 24, 2025

Members of the genus Chlamydia require an intracellular niche for growth and replication, thus highlighting extreme significance its ability to invade epithelial cells—the favored host cell in vivo. Because cells are not phagocytic, uptake must be driven by pathogen. To this end, two bacterial proteins, translocated actin-recruiting protein (TarP) membrane effector A (TmeA), identified trachomatis from infectious chlamydial elementary bodies cytosol facilitate extensive remodeling cortical actin network produce protrusive structures designed pathogen engulfment. Notably, both effectors act promoting highly localized nucleation at sites adhesion. However, they have non-redundant functions, with required optimal dynamics efficient invasion. Finally, these also mediate latter stages invasion process, specifically modulating dynamin 2, a large GTPase critical closure scission invaginating vesicles harboring bodies. In summary, TarP TmeA orchestrate major aspects C.

Language: Английский

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Genomic insights into local-scale evolution of ocular Chlamydia trachomatis strains within and between individuals in Gambian trachoma-endemic villages

Microbial Genomics, Journal Year: 2024, Volume and Issue: 10(3)

Published: March 6, 2024

Trachoma, a neglected tropical disease caused by Chlamydia trachomatis (Ct) serovars A–C, is the leading infectious cause of blindness worldwide. Africa bears highest burden, accounting for over 86 % global trachoma cases. We investigated Ct serovar A (SvA) and B (SvB) whole genome sequences prior to induction mass antibiotic drug administration in The Gambia. Here, we explore factors contributing strain diversification implications evolution within context ocular infection. cohort study 2002–2003 collected swabs across nine Gambian villages during 6 month follow-up study. To genetic diversity between individuals, conducted whole-genome sequencing (WGS) on limited number ( n =43) Ct-positive samples with an omc load ≥10 from four villages. WGS was performed using target enrichment SureSelect Illumina paired-end sequencing. Out 43 samples, 41 provided sufficient quality further analysis. omp analysis revealed that 11 had identity A/HAR13 (NC_007429) 30 B/Jali20 (NC_012686). While SvB formed two distinct village-driven subclades, heterogeneity SvA led formation many individual branches subclade. Comparing their reference strains, B/Jali20, indicated single nucleotide polymorphism accumulation rate 2.4×10 −5 per site year 1.3×10 variants P <0.0001). Variant calling resulted total 1371 (SNVs) frequency >25 sequences, 438 SNVs sequences. Of note, variants, evolutionary pressure recorded genes responsible host cell modulation intracellular survival mechanisms, whereas this mainly essential DNA replication/repair mechanisms protein synthesis. comparison observed separate infection events (4–20 weeks infections) suggested majority variations accumulated host–pathogen interaction such as CTA_0166 (phospholipase D-like protein), CTA_0498 (TarP) CTA_0948 (deubiquitinase). This endemic population focused local adaptation. found different variation pattern chromosomal compared SvB, hinting at potential serovar-specific fitness. These findings may have optimizing control prevention strategies.

Language: Английский

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Autophagy: the misty lands of Chlamydia trachomatis infection

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 6, 2024

are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate replication, these bacteria must engage in host-pathogen interactions to obtain nutrients membranes required for growth of inclusion, thereby sustaining prolonged colonization. Autophagy is highly conserved process delivers cytoplasmic substrates lysosome degradation. Pathogens have developed strategies manipulate and/or exploit autophagy promote their replication persistence. This review delineates recent advances elucidating interplay between

Language: Английский

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Overexpressing the ClpC AAA+ unfoldase accelerates developmental cycle progression in Chlamydia trachomatis

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

ABSTRACT Chlamydia is an obligate intracellular bacterium that undergoes a complex biphasic developmental cycle, alternating between the smaller, infectious, non-dividing elementary body (EB) and larger, non-infectious but dividing reticulate body. Due to differences these functionally morphologically distinct forms, we hypothesize protein degradation essential chlamydial differentiation. The bacterial Clp system, consisting of ATPase unfoldase (e.g., ClpX or ClpC) proteolytic component ClpP), critical for physiology bacteria through its recognition, usually degradation, specific substrates. We observed by transmission electron microscopy overexpression wild-type ClpC, not mutant isoform, in increased glycogen accumulation within vacuolar niche earlier cycle than typically observed. This suggested ClpC activity may increase expression EB-associated genes. Consistent with this, targeted RT-qPCR analyses demonstrated significant several gene transcripts development. These effects were providing strong evidence drives secondary By analyzing global transcriptional response using RNA sequencing, shift canonical late genes other Finally, directly linked production infectious chlamydiae. Conversely, disrupting normal function caused delay progression. Overall, findings provide first mechanistic insight initiation differentiation . IMPORTANCE species are require host cell which complete their unique cycle. differentiates non-replicating form, body, replicating signals drive events characterized. proteases mediating allowing remodeling proteome as organism transitions from one functional form another. previously reported C aseino l ytic p rotease (Clp) system growth. Here, reveal surprising unfoldase, driving chlamydiae during

Language: Английский

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Contributions of diverse models of the female reproductive tract to the study of Chlamydia trachomatis-host interactions

Current Opinion in Microbiology, Journal Year: 2023, Volume and Issue: 77, P. 102416 - 102416

Published: Dec. 15, 2023

Language: Английский

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Chlamydiae as symbionts of photosynthetic dinoflagellates

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Chlamydiae are ubiquitous intracellular bacteria and infect a wide diversity of eukaryotes, including mammals. However, chlamydiae have never been reported to photosynthetic organisms. Here, we describe novel chlamydial genus species, Candidatus Algichlamydia australiensis, capable infecting the dinoflagellate Cladocopium sp. (originally isolated from scleractinian coral). australiensis was confirmed be by fluorescence in situ hybridization confocal laser scanning microscopy temporally stable at population level monitoring its relative abundance across four weeks host growth. Using combination short- long-read sequencing, recovered high-quality (completeness 91.73% contamination 0.27%) metagenome-assembled genome A. australiensis. Phylogenetic analyses show that this taxon represents new species within Simkaniaceae family. possesses all hallmark genes for chlamydiae-host interactions, complete type III secretion system. In addition, IV system is encoded on plasmid has previously observed only three other species. Twenty orthologous groups unique one which structurally similar protein known Cyanobacteria Archaeplastida involved thylakoid biogenesis maintenance, hinting potential interactions with chloroplasts cells. Our study shows symbionts cnidarians, first organism harbor chlamydiae, thereby expanding breadth hosts providing contribution discussion around role establishment primary plastid.

Language: Английский

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