Project description:Methicillin-resistant Staphylococcus aureus clonal complex (CC) 398 has emerged from pigs to cause human infections in Europe and North America. We used a new 62-strain S. aureus microarray (SAM-62) to compare genomes of isolates from three geographical areas (Belgium, Denmark, and Netherlands) to understand how CC398 colonizes different mammalian hosts. The core genomes of 44 pig isolates and 32 isolates from humans did not vary. However, mobile genetic element (MGE) distribution was variable including SCCmec. Phi3 bacteriophage and human specificity genes (chp, sak, scn) were found in invasive human but not pig isolates. SaPI5 and putative ruminant specificity gene variants (vwb and scn) were common but not pig specific. Virulence and resistance gene carriage was host associated but country specific. We conclude MGE exchange is frequent in CC398 and greatest among populations in close contact. This feature may help determine epidemiological associations among isolates of the same lineage. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-120]
Project description:Purpose: The aim of this study was to explore the antibacterial effect and molecular mechanism of gallium nitrate [Ga(NO 3 ) 3 ] against Acinetobacter baumannii from bloodstream infection. Methods: A total of 40 A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. In vitro antibacterial effect of Ga(NO 3 ) 3 was analyzed by micro-dilution method and time-kill assay. The effect of ferric chloride/heme on the antibacterial effect of Ga(NO 3 ) 3 was evaluated. Transcriptome sequencing was performed to elucidate the antibacterial mechanism of gallium nitrate. Mouse infection model was conducted to explore the in vivo efficacy of gallium nitrate . Results: Ga(NO 3 ) 3 exhibited excellent antibacterial effect in RPMI 1 640 medium containing 10% human serum (MICs ranged from 0.06 μg/mL to 0.125 μg/mL), whereas its antibacterial effect was weakened by exogenous ferric chloride/heme. Ga(NO 3 ) 3 inhibited A. baumannii growth in a dose- and time- dependent manner. Ga(NO 3 ) 3 exerted antibacterial effect by up-regulating the expression of genes associated with biosynthesis and transport of siderophore and disrupting multiple iron dependent metabolism processes. Ga(NO 3 ) 3 significantly reduced bacterial load in the neutropenic mouse thigh infection model. Conclusions: This study revealed that Ga(NO 3 ) 3 had excellent antibacterial activity both in vivo and in vitro . It might be a potential drug for treating bloodstream infections of A. baumannii
Project description:Studies on S. aureus sub-populations revealed that genomes are well conserved between isolates from the same lineages despite geographic, temporal and selective diversity. However, variation of hundreds of genes can occur between isolates from different lineages and these genes could be involved in interaction with host components. In this study, we aimed to investigate the diversity of secreted virulence factors in human and zoonotic S. aureus isolates from different clonal complexes. We focused on the S. aureus clonal complexes (CC) 8 and CC22 as dominant human lineages, and CC398 as dominant livestock-associated MRSA (LA-MRSA) which is disseminating rapidly. To study the diversity of secreted virulence factors, we compared their extracellular proteomes using label-free LC-MS/MS analysis. A common protein database was created based on DNA sequencing data and PAN genome IDs.
Project description:THE CORRELATION BETWEEN ANTIBIOTIC SUSCEPTIBILITY, VIRULOME, AND CLINICAL OUTCOME IN EUROPEAN INFANTS LESS THAN 90 DAYS AFFECTED BY BLOODSTREAM INFECTIONS CAUSED BY ENTEROBACTERALES
Project description:Livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) CC398 isolated from UK animals belong to European lineages