Chlamydiosis in Animals

Animals, Год журнала: 2024, Номер 14(21), С. 3130 - 3130

Опубликована: Окт. 30, 2024

The

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Recognition ofChlamydia trachomatisby Toll-Like Receptor 9 is altered during persistence

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 8, 2024

ABSTRACT Toll-like receptor 9 (TLR9) is an innate immune that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA. Previous bioinformatic studies have indicated the genome of human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, correlative implied a link between (hTLR9) genotype variants susceptibility infection. Here we present our evaluation potential C. gDNA its recognition by hTLR9– murine (mTLR9)-expressing cells. We confirm hTLR9 colocalizes with chlamydial inclusions pro-monocytic cell line, U937. Utilizing HEK293 reporter lines, demonstrate purified DNA from can stimulate signaling, albeit at lower levels than prepared other Gram-negative bacteria. Interestingly, found while capable signaling through mTLR9 during live infections non-phagocytic only occurs later developmental time points. Chlamydia-specific induction blocked when protein synthesis inhibited prior RB-to-EB conversion exacerbated inhibition lipooligosaccharide biosynthesis. The aberrance / persistence also significantly alters signaling. Our observations support hypothesis released appreciable bacterium replicative infectious forms treatment antibiotics targeting peptidoglycan assembly.

Язык: Английский

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Analyzing RNA-Seq Data from Chlamydia with Super Broad Transcriptomic Activation: Challenges, Solutions, and Implications for Other Systems

Опубликована: Май 21, 2024

RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to immediate early

Язык: Английский

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Recognition of Chlamydia trachomatis by Toll-like receptor 9 is altered during persistence

Infection and Immunity, Год журнала: 2024, Номер 92(7)

Опубликована: Июль 11, 2024

ABSTRACT Toll-like receptor 9 (TLR9) is an innate immune that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA (gDNA). Previous bioinformatic studies have demonstrated the genome of human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, correlative implied a link between (hTLR9) genotype variants susceptibility infection. Here, we present our evaluation potential C. gDNA its recognition by hTLR9- murine (mTLR9)-expressing cells. Utilizing reporter cell lines, demonstrate purified from can stimulate hTLR9 signaling, albeit at lower levels than prepared other Gram-negative bacteria. Interestingly, found while capable signaling through mTLR9 during live infections HEK293 only occurs later developmental time points. Chlamydia-specific induction blocked when protein synthesis inhibited prior RB-to-EB conversion, exacerbated inhibition lipooligosaccharide biosynthesis, significantly altered aberrance/persistence. Our observations support hypothesis chlamydial released conversion pathogen’s replicative infectious forms treatment with antibiotics targeting peptidoglycan assembly. Given inclusions do not co-localize TLR9-containing vacuoles pro-monocytic line U937, findings also hint egress inclusion, traffics via as yet unknown pathway.

Язык: Английский

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Analyzing RNA-Seq data from Chlamydia with super broad transcriptomic activation: challenges, solutions, and implications for other systems

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Авг. 25, 2024

RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to immediate early Chlamydia spp., obligate intracellular bacteria. These arise from their reliance assumptions that do not hold in scenarios characterized by extensive transcriptomic activation limited repression. Standard analyses using unique chlamydial RNA-Seq reads alone identify nearly 300 upregulated about downregulated genes, significantly deviating actual read trends. By incorporating both host or adjusting for total depth, revised normalization methods each detected over 700 genes 30 fewer closely aligned with observed data. Further validation through qRT-PCR confirmed effectiveness these adjusted approaches capturing true extent during phase infection. This study highlights limitations tools activation, such as spp. Our methods, provide a more accurate representation gene dynamics. may inform similar adjustments other systems unbalanced dynamics, enhancing accuracy analysis.

Язык: Английский

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A host-directed adjuvant resuscitates and sensitizes intracellular bacterial persisters to antibiotics

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Abstract There are two major problems in the field of antimicrobial chemotherapy–antibiotic resistance and antibiotic tolerance. In case tolerance, antibiotics fail to kill bacteria as their phenotypic state affords them protection from bactericidal activity antibiotic. Antibiotic tolerance can affect an entire bacterial population, or a subset cells known persister cells. Interaction with host induces formation numerous pathogens, reactive oxygen nitrogen species production being heavily implicated collapse energy levels entrance into tolerant state. Here, we developed high-throughput screen identify modulators for intracellular Staphylococcus aureus . The identified compound, KL1 , increases sensitizes population antibiotics, without causing cytotoxicity outgrowth. We demonstrate that exhibits adjuvant murine model S. bacteremia infection Salmonella Typhimurium Transcriptomic analysis further studies on its mechanism action reveal modulates immune response genes suppresses macrophages, alleviating one stressors induce Our findings highlight potential target by stimulating metabolism encourage larger efforts address at host–pathogen interface, particularly within milieu.

Язык: Английский

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The SWIB domain-containing DNA topoisomerase I of Chlamydia trachomatis mediates DNA relaxation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 3, 2024

The obligate intracellular bacterial pathogen,

Язык: Английский

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