Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical findings relating to 11 patients in Hong Kong (HK) and to 43 patients described elsewhere, all with Streptococcus zooepidemicus septicaemia, are reviewed. There was a particular association with cardiovascular disease (27%) with seven cases of endocarditis, three of abdominal aortic aneurysm and two of deep venous thrombosis. Associations not previously reported included two cases of pharyngitis and two patients with persistent post-operative fever. The overall mortality was 22%. Both human and porcine strains of S. zooepidemicus from HK did not hydrolyse aesculin in contrast to the aesculin-positive biotypes reported previously. HK strains also had very mucoid colonies and capsules of hyaluronic acid were seen in electron micrographs. Samples of chromosomal DNA, extracted by means of HindIII restriction endonuclease, of strains from human beings and pigs were identical. The MIC of penicillin for all strains was less than or equal to 0.03 mg/l but the MBC for all was greater than 32 mg/l. Penicillin alone is generally sufficient for cure but combination with an aminoglycoside may be indicated in seriously ill patients. In our locality, pigs were incriminated as a possible source of human infection whereas consumption of contaminated dairy products is important elsewhere.
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PMID:Streptococcus zooepidemicus (Lancefield group C) septicaemia in Hong Kong. 227 71

Evolutionary trajectories and mutational landscapes of drug-resistant bacteria are influenced by cell-intrinsic and extrinsic factors. In this study, I demonstrated that loss of the Lon protease altered susceptibility of Escherichia coli to trimethoprim and that these effects were strongly contingent on the drug concentration and genetic background. Lon, an AAA+ ATPase, is a bacterial master regulator protease involved in cytokinesis, suppression of transposition events, and clearance of misfolded proteins. I show that Lon deficiency enhances intrinsic drug tolerance at sub-MIC levels of trimethoprim. As a result, loss of Lon, though disadvantageous under drug-free conditions, has a selective advantage at low concentrations of trimethoprim. At high drug concentrations, however, Lon deficiency is detrimental for E. coli I show that the former is explained by suppression of drug efflux by Lon, while the latter can be attributed to SulA-dependent hyperfilamentation. On the other hand, deletion of lon in a trimethoprim-resistant mutant E. coli strain (harboring the Trp30Gly dihydrofolate reductase [DHFR] allele) directly potentiates resistance by enhancing the in vivo stability of mutant DHFR. Using extensive mutational analysis at 3 hot spots of resistance, I show that many resistance-conferring mutations render DHFR prone to proteolysis. This trade-off between gaining resistance and losing in vivo stability limits the number of mutations in DHFR that can confer trimethoprim resistance. Loss of Lon expands the mutational capacity for acquisition of trimethoprim resistance. This paper identifies the multipronged action of Lon in trimethoprim resistance in E. coli and provides mechanistic insight into how genetic backgrounds and drug concentrations may alter the potential for antimicrobial resistance evolution.IMPORTANCE Understanding the evolutionary dynamics of antimicrobial resistance is vital to curb its emergence and spread. Being fundamentally similar to natural selection, the fitness of resistant mutants is a key parameter to consider in the evolutionary dynamics of antimicrobial resistance (AMR). Various intrinsic and extrinsic factors modulate the fitness of resistant bacteria. This study demonstrated that Lon, a bacterial master regulator protease, influences drug tolerance and resistance. Lon is a key regulator of several fundamental processes in bacteria, including cytokinesis. I demonstrated that Lon deficiency produces highly contingent phenotypes in E. coli challenged with trimethoprim and can expand the mutational repertoire available to E. coli to evolve resistance. This multipronged influence of Lon on drug resistance provides an illustrative instance of how master regulators shape the response of bacteria to antibiotics.
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PMID:Highly Contingent Phenotypes of Lon Protease Deficiency in Escherichia coli upon Antibiotic Challenge. 3174 Apr 90