Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection

Gérard, Hervé C.; Freise, Julia; Zhao, Wei; Roberts, George G.; Rudy, Debbi; Krauß-Opatz, Birgit; Köhler, Lars; Zeidler, Henning; Schumacher, H. Ralph; Whittum-Hudson, Judith A.; Hudson, Alan P.

doi:10.1016/s1286-4579(01)01504-0

Cited by 81 publications

(79 citation statements)

References 28 publications

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“…While this has not been observed previously with an antibiotic, TCA cycle gene induction has been reported in response to neutrophil phagocytosis (44) and during entry into stationary-phase growth (25). The up-regulation of carbon flux into and through the TCA cycle is particularly interesting because TCA cycle activity has been shown to be associated with virulence, survival, and persistence of S. aureus and several other pathogens (3,10,17,28,30,39,40). In total, the data suggest that ciprofloxacin induces significant changes in carbohydrate uptake and metabolism, with an increased reliance on the TCA cycle for metabolism and/or energy production.…”

Section: Discussionmentioning

confidence: 95%

Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

Jones²,

et al. 2007

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Staphylococcus aureus infections can be difficult to treat due to both multidrug resistance and the organism's remarkable ability to persist in the host. Persistence and the evolution of resistance may be related to several complex regulatory networks, such as the SOS response, which modifies transcription in response to environmental stress. To understand how S. aureus persists during antibiotic therapy and eventually emerges resistant, we characterized its global transcriptional response to ciprofloxacin. We found that ciprofloxacin induces prophage mobilization as well as significant alterations in metabolism, most notably the up-regulation of the tricarboxylic acid cycle. In addition, we found that ciprofloxacin induces the SOS response, which we show, by comparison of a wild-type strain and a non-SOS-inducible lexA mutant strain, includes the derepression of 16 genes. While the SOS response of S. aureus is much more limited than those of Escherichia coli and Bacillus subtilis, it is similar to that of Pseudomonas aeruginosa and includes RecA, LexA, several hypothetical proteins, and a likely error-prone Y family polymerase whose homologs in other bacteria are required for induced mutation. We also examined induced mutation and found that either the inability to derepress the SOS response or the lack of the LexA-regulated polymerase renders S. aureus unable to evolve antibiotic resistance in vitro in response to UV damage. The data suggest that up-regulation of the tricarboxylic acid cycle and induced mutation facilitate S. aureus persistence and evolution of resistance during antibiotic therapy.

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Section: Discussionmentioning

confidence: 95%

Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

Jones²,

et al. 2007

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confidence: 82%

“…The relative independence of the latter two groups of pathogens on the host for amino acids suggests that the TCA cycle may perform important functions in these organisms during pathogenesis. This supposition is supported by extensive experimental data demonstrating that TCA cycle function is involved in virulence, survival, and persistence (11,20,34,36,51,53).Transcriptional regulation of TCA cycle genes is primarily dependent on the presence of oxygen and the carbon source (10,21,22,54,55). In gram-negative bacteria, TCA cycle activity is greatest during aerobic growth in a medium containing a carbon source capable of being converted into acetylcoenzyme A.…”

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confidence: 91%

Correlation of Acetate Catabolism and Growth Yield inStaphylococcus aureus: Implications for Host-Pathogen Interactions

Saïd-Salim²,

et al. 2003

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Recently, we reported that the prototypical Staphylococcus aureus strain RN6390 (a derivative of NCTC 8325) had significantly reduced aconitase activity relative to a diverse group of S. aureus isolates, leading to the hypothesis that strain RN6390 has impaired tricarboxylic acid (TCA) cycle-mediated acetate catabolism. Analysis of the culture supernatant from RN6390 confirmed that acetate was incompletely catabolized, suggesting that the ability to catabolize acetate can be lost by S. aureus. To test this hypothesis, we examined the carbon catabolism of the S. aureus strains whose genome sequences are publicly available. All strains catabolized glucose and excreted acetate into the culture medium. However, strains NCTC 8325 and N315 failed to catabolize acetate during the postexponential growth phase, resulting in significantly lower growth yields relative to strains that catabolized acetate. Strains NCTC 8325 and RN6390 contained an 11-bp deletion in rsbU, the gene encoding a positive regulator of the alternative sigma factor B encoded by sigB. An isogenic derivative strain of RN6390 containing the wild-type rsbU gene had significantly increased acetate catabolism, demonstrating that B is required for acetate catabolism. Taken together, the data suggest that naturally occurring mutations can alter the ability of S. aureus to catabolize acetate, a surprising discovery, as TCA cycle function has been demonstrated to be involved in the virulence, survival, and persistence of several pathogenic organisms. Additionally, these mutations decrease the fitness of S. aureus by reducing the number of progeny placed into subsequent generations, suggesting that in certain situations a decreased growth yield is advantageous.The tricarboxylic acid (TCA) cycle is an essential source of energy and biosynthetic intermediates for many organisms. Pathogenic organisms can be divided into three categories based on the TCA cycle. Those in the first group do not possess a TCA cycle and have become dependent upon the host to provide amino acids or intermediates for biosynthesis (e.g., Borrelia burgdorferi and Streptococcus pyogenes). Those in the second group have an incomplete TCA cycle and are auxotrophic for some amino acids (e.g., Yersinia pestis and Haemophilus influenzae). Lastly, the third group is characterized as having a complete TCA cycle (e.g., Pseudomonas aeruginosa and Staphylococcus aureus) but, depending upon other metabolic limitations, can be auxotrophic for certain amino acids. The relative independence of the latter two groups of pathogens on the host for amino acids suggests that the TCA cycle may perform important functions in these organisms during pathogenesis. This supposition is supported by extensive experimental data demonstrating that TCA cycle function is involved in virulence, survival, and persistence (11,20,34,36,51,53).Transcriptional regulation of TCA cycle genes is primarily dependent on the presence of oxygen and the carbon source (10,21,22,54,55). In gram-negative bacteria, TCA cycle activity is g...

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“…The presence of C. pneumoniae in persistent infection is characterized by an absence of culturability [7], in addition to altered bacterial RNA and protein levels [8][9][10][11], morphologically altered chlamydial bodies [8] and increased resistance to antimicrobials, such as azithromycin or clarithromycin, frequently used for the treatment of C. pneumoniae infection [12]. The mechanisms leading to persistent C. pneumoniae infection remain unclear; however, infection in reported cases occurred during an uncompleted developmental cycle with a lack of maturation of the EB, and an absence of bacterial metabolic activity caused a decrease in sensitivity to the antibiotics used.…”

Section: Introductionmentioning

confidence: 99%

Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells

Ishida

Yamazaki

Motohashi

et al. 2012

Journal of Infection and Chemotherapy

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Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection

Cited by 81 publications

References 28 publications

Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

Correlation of Acetate Catabolism and Growth Yield inStaphylococcus aureus: Implications for Host-Pathogen Interactions

Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells

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