Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mutant of Klebsiella aerogenes lacking glutamate synthase activity (asm-200) is blocked in only one pathway of glutamate synthesis and can still use glutamate dehydrogenase to produce glutamate when ammonia in sufficient concentration, i.e., higher than 1 mM, is provided in the medium. However, a mutant that has neither glutamate synthase nor glutamate dehydrogenase activities (asm-200, gdhD1) requires glutamate. Transductants obtained by phage grown on wild-type cells of this double mutant, selected on medium containing less than 1 mM ammonia, regain glutamate synthase but not glutamate dehydrogenase. Surprisingly, these gdhD1 transductants grow as well in a variety of media as does a strain with glutamate dehydrogenase activity. Furthermore, transductions with these and other mutants indicate that the genes encoding glutamate synthase, glutamate dehydrogenase, glutamine synthetase, and citrate synthase are not closely linked.
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PMID:Mutants of Klebsiella aerogenes lacking glutamate dehydrogenase. 414 14

The activities of pyruvate kinase (PK), pyruvate: formate-lyase (PFL), pyruvate dehydrogenase (PDH), and citrate synthase (CS) involved in the anaerobic glycerol conversion by Klebsiella pneumoniae were studied in continuous culture under conditions of steady states and sustained oscillations. Both the in vitro and in vivo activities of PK, PFL, and PDH are strongly affected by the substrate concentration and its uptake rate, as is the in vitro activity of CS. The flux from phosphoenolpyruvate to pyruvate is found to be mainly regulated on a genetic level by the synthesis rate of PK, particularly at low substrate concentration and low growth rate. In contrast, the conversion of pyruvate to acetyl-CoA is mainly regulated on a metabolic level by the in vivo activities of PFL and PDH. The ratio of in vitro to in vivo activities is in the range of 1 to 1.5 for PK, 5 to 17 for PFL and 5 to 80 for PDH under the experimental conditions. The regulation of in vivo activity and synthesis of these enzymes is sensitive to fluctuations of culture conditions, leading to oscillations of both the in vitro and in vivo activities. In particular, PFL is strongly affected during oscillations; its average in vitro activity is only about half of its corresponding steady-state value under similar environmental conditions. The average in vitro activities of PDH and PK under oscillations are close to their corresponding steady-state values. In contrast to all other enzymes measured for the glycerol metabolism by K. pneumoniae PFL and PDH are more effectively in vivo utilized under oscillations than under steady state, underlining the peculiar role of pyruvate metabolism in the dynamic responses of the culture.
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PMID:Kinetic, dynamic, and pathway studies of glycerol metabolism by Klebsiella pneumoniae in anaerobic continuous culture: IV. Enzymes and fluxes of pyruvate metabolism. 1009 70

Klebsiella pneumoniae (Kp), one of the most common causes of healthcare-associated infections, increases patient morbidity, mortality, and hospitalization costs. Kp must acquire nutrients from the host for successful infection; however, the host is able to prevent bacterial nutrient acquisition through multiple systems. This includes the innate immune protein lipocalin 2 (Lcn2), which prevents Kp iron acquisition. To identify novel Lcn2-dependent Kp factors that mediate evasion of nutritional immunity during lung infection, we undertook an InSeq study using a pool of >20,000 transposon mutants administered to Lcn2+/+ and Lcn2-/- mice. Comparing transposon mutant frequencies between mouse genotypes, we identified the Kp citrate synthase, GltA, as potentially interacting with Lcn2, and this novel finding was independently validated. Interestingly, in vitro studies suggest that this interaction is not direct. Given that GltA is involved in oxidative metabolism, we screened the ability of this mutant to use a variety of carbon and nitrogen sources. The results indicated that the gltA mutant has a distinct amino acid auxotrophy rendering it reliant upon glutamate family amino acids for growth. Deletion of Lcn2 from the host leads to increased amino acid levels in bronchioloalveolar lavage fluid, corresponding to increased fitness of the gltA mutant in vivo and ex vivo. Accordingly, addition of glutamate family amino acids to Lcn2+/+ bronchioloalveolar lavage fluid rescued growth of the gltA mutant. Using a variety of mouse models of infection, we show that GltA is an organ-specific fitness factor required for complete fitness in the spleen, liver, and gut, but dispensable in the bloodstream. Similar to bronchioloalveolar lavage fluid, addition of glutamate family amino acids to Lcn2+/+ organ lysates was sufficient to rescue the loss of gltA. Together, this study describes a critical role for GltA in Kp infection and provides unique insight into how metabolic flexibility impacts bacterial fitness during infection.
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PMID:The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection. 3144 51

Antimicrobial resistance (AMR) is a current major health issue, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of AMR. Pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Mycobacterium tuberculosis among others are clear examples of antibiotic-resistant threats. Biosurfactants have recently emerged as a potential new generation of anti-adhesive and anti-biofilm agents; mannosylerythritol lipids (MELs) are biosurfactants produced by a range of fungi. A range of structural variants of MELs can be formed and the proportion of each isomer in the fermentation depends on the yeast used, the carbon substrate used for growth and the duration of the fermentation. In order to allow assessment of the possible functions of MELs as antimicrobial molecules, small quantities of MEL were produced by controlled fermentation. Fermentations of the yeast Pseudozyma aphidis using rapeseed oil as a carbon source yielded up to 165 gMELs/kgSubstrate. The MELs formed by this strain was a mixture of MEL-A, MEL-B, MEL-C and MEL-D. The MELs produced were tested against S. aureus ATCC 6538 on pre-formed biofilm and on co-incubation biofilm experiments on silicone discs; showing a disruption of biomass, reduction of the biofilm metabolic activity and a bacteriostatic/bactericidal effect confirmed by a release of oxygen uptake [Formula: see text], the reduction of citrate synthase activity and scanning electron microscopy. The results show that MELs are promising antimicrobial molecules for biomedical technological applications that could be studied in detail in large-scale systems and in conjunction with animal tissue models.
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PMID:Production of Mannosylerythritol Lipids (MELs) to be Used as Antimicrobial Agents Against S. aureus ATCC 6538. 3212 84