scholarly journals Chlamydia trachomatis Lacks an Adaptive Response to Changes in Carbon Source Availability

2004 ◽  
Vol 72 (7) ◽  
pp. 4286-4289 ◽  
Author(s):  
Tracy L. Nicholson ◽  
Karen Chiu ◽  
Richard S. Stephens
Keyword(s):  
Chlamydia Trachomatis ◽  
Carbon Source ◽  
Adaptive Response ◽  
Environmental Changes ◽  
Carbon Sources ◽  
Transcriptional Response ◽  
Free Living ◽  
Regulate Gene Expression ◽  
Obligate Intracellular ◽  
Obligate Intracellular Pathogen

ABSTRACT Most bacteria coordinately regulate gene expression as an adaptive response to a variety of environmental changes. One key environmental cue is the carbon source necessary for central metabolism. We used microarray analysis to monitor the global transcriptional response of the obligate intracellular pathogen Chlamydia trachomatis to the presence of glycolytic and gluconeogenic carbon sources. In contrast to free-living bacteria, changing the carbon source from glucose to glutamate or α-ketoglutarate had little effect on the global gene transcription of C. trachomatis.

scholarly journals A link between gut community metabolism and pathogenesis: molecular hydrogen-stimulated glucarate catabolism aids Salmonella virulence

Open Biology ◽  
2013 ◽  
Vol 3 (12) ◽  
pp. 130146 ◽  
Author(s):  
Reena Lamichhane-Khadka ◽  
Stéphane L. Benoit ◽  
Susan E. Maier ◽  
Robert J. Maier
Keyword(s):  
Carbon Source ◽  
Molecular Hydrogen ◽  
Carbon Sources ◽  
Transcriptional Response ◽  
Hydrogen Gas ◽  
Serovar Typhimurium ◽  
Salmonella Virulence ◽  
Alternative Carbon Source ◽  
Dependent Growth ◽  
High Level

Glucarate, an oxidized product of glucose, is a major serum organic acid in humans. Still, its role as a carbon source for a pathogen colonizing hosts has not been studied. We detected high-level expression of a potential glucarate permease encoding gene gudT when Salmonella enterica serovar Typhimurium are exposed to hydrogen gas (H 2 ), a gaseous by-product of gut commensal metabolism. A gudT strain of Salmonella is deficient in glucarate-dependent growth, however, it can still use other monosaccharides, such as glucose or galactose. Complementation of the gudT mutant with a plasmid harbouring gudT restored glucarate-dependent growth to wild-type (WT) levels. The gudT mutant exhibits attenuated virulence: the mean time of death for mice inoculated with WT strain was 2 days earlier than for mice inoculated with the gudT strain. At 4 days postinoculation, liver and spleen homogenates from mice inoculated with a gudT strain contained significantly fewer viable Salmonella than homogenates from animals inoculated with the parent. The parent strain grew well H 2 -dependently in a minimal medium with amino acids and glucarate provided as the sole carbon sources, whereas the gudT strain achieved approximately 30% of the parent strain's yield. Glucarate-mediated growth of a mutant strain unable to produce H 2 was stimulated by H 2 addition, presumably owing to the positive transcriptional response to H 2 . Gut microbiota-produced molecular hydrogen apparently signals Salmonella to catabolize an alternative carbon source available in the host. Our results link a gut microbiome-produced diffusible metabolite to augmenting bacterial pathogenesis.

scholarly journals Persistence alters the interaction between Chlamydia trachomatis and its host cell.

2021 ◽  
Author(s):  
Mary R. Brockett ◽  
George W. Liechti
Keyword(s):  
Chlamydia Trachomatis ◽  
Effector Proteins ◽  
Developmental Cycle ◽  
Intracellular Pathogen ◽  
Obligate Intracellular ◽  
Peptide Labeling ◽  
Extracellular Form ◽  
Response To Stress ◽  
Obligate Intracellular Pathogen ◽  
Late Stages

In response to stress, the obligate intracellular pathogen Chlamydia trachomatis stops dividing and halts its biphasic developmental cycle. The infectious, extracellular form of this bacterium is highly susceptible to killing by the host immune response, and by pausing development Chlamydia can survive in an intracellular, ‘aberrant’ state for extended periods of time. The relevance of these aberrant forms has long been debated, and many questions remain concerning how they contribute to the persistence and pathogenesis of the organism. Using reporter cell lines, fluorescence microscopy, and a di-peptide labeling strategy, we measured the ability of C. trachomatis to synthesize, assemble, and degrade peptidoglycan under various aberrance-inducing conditions. We found that all aberrance-inducing conditions affect chlamydial peptidoglycan, and that some actually halt the biosynthesis pathway early enough to prevent the release of an immunostimulatory peptidoglycan component, muramyl tripeptide. In addition, utilizing immunofluorescence and electron microscopy, we determined that the induction of aberrance can detrimentally affect the development of the microbe’s pathogenic vacuole (the inclusion). Taken together, our data indicate that aberrant forms of Chlamydia generated by different environmental stressors can be sorted into two broad categories based on their ability to continue releasing peptidoglycan-derived, immunostimulatory muropeptides and their ability to secrete effector proteins that are normally expressed at the mid- and late- stages of the microbe’s developmental cycle. Our findings reveal a novel, immuno-evasive feature inherent to a subset of aberrant chlamydial forms and provide clarity and context to the numerous persistence mechanisms employed by these ancient, genetically-reduced microbes.

scholarly journals A Dynamic, Ring-Forming Bactofilin Critical for Maintaining Cell Size in the Obligate Intracellular Bacterium Chlamydia trachomatis

2021 ◽  
Author(s):  
Mary R. Brockett ◽  
Junghoon Lee ◽  
John V. Cox ◽  
George W. Liechti ◽  
Scot P. Ouellette
Keyword(s):  
Cell Division ◽  
Chlamydia Trachomatis ◽  
Cell Size ◽  
Cytoskeletal Proteins ◽  
Intracellular Bacterium ◽  
Developmental Cycle ◽  
Obligate Intracellular Bacterium ◽  
Obligate Intracellular ◽  
Peptidoglycan Biosynthesis ◽  
Obligate Intracellular Pathogen

Bactofilins are polymer-forming cytoskeletal proteins that are widely conserved in bacteria. Members of this protein family have diverse functional roles such as orienting subcellular molecular processes, establishing cell polarity, and aiding in cell shape maintenance. Using sequence alignment to the conserved bactofilin domain, we identified a bactofilin ortholog, BacACT, in the obligate intracellular pathogen Chlamydia trachomatis. Chlamydia species are obligate intracellular bacteria that undergo a developmental cycle alternating between infectious, non-dividing EBs (elementary bodies) and non-infectious, dividing RBs (reticulate bodies). As Chlamydia divides by a polarized division process, we hypothesized that BacACT may function to establish polarity in these unique bacteria. Utilizing a combination of fusion constructs and high-resolution fluorescence microscopy, we determined that BacACT forms dynamic, membrane-associated filament- and ring-like structures in Chlamydia’s replicative RB form. Contrary to our hypothesis, these structures are distinct from the microbe’s cell division machinery and do not colocalize with septal peptidoglycan or MreB, the major organizer of the bacterium’s division complex. Bacterial two-hybrid assays demonstrated BacACT interacts homotypically but does not directly interact with proteins involved in cell division or peptidoglycan biosynthesis. To investigate the function of BacACT in chlamydial development, we constructed a conditional knockdown strain using a newly developed CRISPR interference system. We observed that reducing bacACT expression significantly increased chlamydial cell size. Normal RB morphology was restored when an additional copy of bacACT was expressed in trans during knockdown. These data reveal a novel function for chlamydial bactofilin in maintaining cell size in this obligate intracellular bacterium.

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