Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

EFFECTS OF L-CARNITINE ON TISSUE LEVELS OF ACYL CARNITINE, ACYL COENZYME A AND HIGH ENERGY PHOSPHATE IN ISCHEMIC DOG HEARTS

In order to evaluate the protective effects of L-carnitine on ischemic myocardium, its effects on tissue levels of acyl carnitine, acyl coenzyme A (CoA) and high energy phosphate were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of left anterior descending coronary artery for 15 minutes. L-carnitine ( 100 mg/kg) was administered intravenously prior to coronary ligation. In ischemic myocardium, tissue levels of free carnitine decreased from 1043 ± 358 to 623 ± 180 n mol/g (p<0.001). On the other hand, long chain acyl carnitine increased from 214 ± 54 to 498 ± 149 n mol/g (p<0.001) and long chain acyl CoA increased from 15.7 ± 4.8 to 23.2 ± 5.4 n mol/g (p<0.01 ). Pretreatment of L-carnitine increased tissue levels of free carnitine to 863 ± 318 n mol/g (p<0.005) and decreased long chain acyl carnitine and long chain acyl CoA to 368 ±128 n mol/g (p<0.02) and 19.2 ± 6.5 n mol/g (p<0.1) respectively. Tissue levels of adenosine triphosphate (ATP) that was reduced by myocardial ischemia from 5.43± 0.67 to 2.80 ± 0.58 μ mol/g (p<0.001) was increased to 3.28 ± 0.63 μ mol/g (p< 0.02) by L-carnitine. Positive correlation was observed between ATP and free carnitine (p<0.01). On the other hand, negative correlation was observed not only between ATP and the ratio of long chain acyl CoA to free carnitine but also between ATP and the ratio of long chain acyl carnitine to free carnitine (p<0.01 respectively). These results suggest that the accumulation of long chain acyl carnitine may play an important role on cellular damage in ischemic myocardium and that administration of exogenous L-carnitine is beneficial for the protection of ischemic myocardium, probably because it reduces the accumulation of long chain acyl carnitine as well as long chain acyl CoA.rights:社団法人日本循環器学会rights:本文データは学協会の許諾に基づきJournal Archiveから複製したものであ