Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of infective endocarditis is underestimated in solid organ transplant recipients. The spectrum of pathogens is different from the general population. The authors report the successful treatment of a 58-year-old woman with infective endocarditis caused by atypical microorganism and presented with atypical manifestations. Past history of the patient included alcoholic liver cirrhosis and cadaver liver transplantation in February 2000. One year after liver transplantation hepatitis B virus infection was diagnosed and treated with antiviral agents. In July 2007 hemodialysis was started due to progressive chronic kidney disease caused by calcineurin toxicity. In November 2013 the patient presented with transient aphasia. Transesophageal echocardiography revealed vegetation in the aortic valve and brain embolization was identified on magnetic resonance images. Initial treatment consisted of a 4-week regimen with ceftriaxone (2 g daily) and gentamycin (60 mg after hemodialysis). Blood cultures were all negative while serology revealed high titre of antibodies against Chlamydia pneumoniae. Moxifloxacin was added as an anti-chlamydial agent, but neurologic symptoms returned. After coronarography, valvular surgery and coronary artery bypass surgery were performed which resulted in full clinical recovery of the patient.
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PMID:[Infective endocarditis caused by Chlamydia pneumoniae after liver transplantation. Case report]. 2600 49

Chlamydiae are obligate intracellular Gram-negative bacterial pathogens that undergo an essential, but poorly understood, biphasic developmental cycle transitioning between the infectious elementary body and the replicative reticulate body. Ser/Thr/Tyr phosphorylation has been increasingly recognized for its role in regulating bacterial physiology. Chlamydia spp. encode two Hanks'-type kinases in addition to a type 2C protein phosphatase (PP2C; CppA) and appears capable of global protein phosphorylation. While these findings substantiate the importance of protein phosphorylation in Chlamydia, the physiological impact of protein phosphorylation remains enigmatic. In this study, we investigated the in vivo role of CppA by using recombinant protein point mutants and small-molecule inhibitors. Recombinant CppA (rCppA) amino acid point mutants based upon missense mutations identified in growth-deficient Chlamydia trachomatis strains exhibited reduced, but not a complete loss of, phosphatase activity toward p-nitrophenyl phosphate (pNPP) and phosphopeptides. To more directly explore the importance of CppA in chlamydial development, we implemented a chemical "knockout" approach using derivatives of 5,5'-methylenedisalicylic acid (MDSA). Several MDSA derivatives significantly reduced CppA activity in vitro and the growth of C. trachomatis L2, C. trachomatis D, and Chlamydia muridarum in a cell culture infection model. The inhibition of C. trachomatis L2 growth was more pronounced when treated at earlier infection time points, and the removal of the inhibitors after 12 h postinfection did not rescue progeny production. Our findings revealed that altered CppA activity reduces chlamydial growth and that CppA function is likely crucial for early differentiation events. Collectively, our findings further support the importance of the protein phosphorylation network in chlamydial development.IMPORTANCEChlamydia is a significant cause of disease in humans, including sexually transmitted infections, the ocular infection trachoma, and pneumonia. Despite the critical roles of protein phosphatases in bacterial physiology, their function in pathogenesis is less clear. Our findings demonstrate that CppA, a broad-specificity type 2C protein phosphatase (PP2C), is critical for chlamydial development and further substantiate reversible phosphorylation as a key regulatory mechanism in Chlamydia Additionally, our work highlights the potential of CppA to serve as a novel target for future therapeutic strategies and supports the feasibility of designing more potent PP2C phosphatase inhibitors for Chlamydia and other pathogenic bacteria.
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PMID:Inhibition of the Protein Phosphatase CppA Alters Development of Chlamydia trachomatis. 3003 48