Project description:Bacteria can circumvent the effect of antibiotics by transitioning to a poorly understood physiological state that does not involve conventional genetic elements of resistance. Here we examine antibiotic susceptibility with a Class A β-lactamase+ invasive strain of Klebsiella pneumoniae that was isolated from a lethal outbreak within laboratory colonies of Chlorocebus aethiops sabaeus monkeys. Bacterial responses to the ribosomal synthesis inhibitors streptomycin and doxycycline resulted in distinct proteomic adjustments that facilitated decreased susceptibility to each antibiotic.
Project description:Compared with HKE9, HKE9-M-rpoS (rpoS knockout in hypervirulent Klebsiella pneumoniae strain HKE9) had 624 genes expressed significantly different, among which 148 genes were significantly up-regulated and 476 genes were significantly down-regulated, 586 genes on chromosomes, 10 genes on circular plasmid and 28 genes on linear plasmid; HKE9-C-M-rpoS had 746 genes expressed significantly different, among which 286 genes were significantly up-regulated and 460 genes were significantly down-regulated, 727 genes on chromosomes, 11 genes on circular plasmid and 8 genes on linear plasmid. Compared with HKE9-M-rpoS, HKE9-C-M-rpoS (rpoS complement in strain HKE9-M-rpoS) had 509 genes expressed significantly different, among which 324 genes were significantly up-regulated and 185 genes were significantly down-regulated, 458 genes on chromosomes, 3 genes on circular plasmid and 48 genes on linear plasmid.
Project description:Detection and characterization of a Klebsiella oxytoca isolate carrying NDM-1-encoding plasmid, NDM-5-carrying plasmid and KPC-2-harbouring
Project description:The study aimed to characterize plasmids mediating carbepenem resistance in Klebsiella pneumoniae in Pretoria, South Africa. We analysed 56 K. pneumoniae isolates collected from academic hospital around Pretoria. Based on phenotypic and molecular results of these isolates, 6 representative isolates were chosen for further analysis using long reads sequencing platform. We observed multidrug resistant phenotype in all these isolates, including resistance to aminoglycosides, tetracycline, phenicol, fosfomycin, floroquinolones, and beta-lactams antibiotics. The blaOXA-48/181 and blaNDM-1/7 were manily the plasmid-mediated carbapenemases responsible for carbapenem resistance in the K. pneumoniae isolates in these academic hospitals. These carbapenemase genes were mainly associated with plasmid replicon groups IncF, IncL/M, IncA/C, and IncX3. This study showed plasmid-mediated carbapenemase spread of blaOXA and blaNDM genes mediated by conjugative plasmids in Pretoria hospitals.
Project description:With increasingly concerning strains of antimicrobial resistant strains of the commensal, gram-negative bacteria Klebsiella pneumoniae emerging, there is a pressing need to better understand the pathogen and mechanisms behind its pathogenicity. This study investigated the regulatory mechanisms in strain MGH 78578 of two major sigma factors, the house-keeping sigma factor RpoD, and the general stress response sigma factor RpoS, in mid-exponential and early stationary phase using chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) followed by deep sequencing. Combining ChIP-exo and transcriptome analysis allowed for the determination of sigma factor binding sites, binding motifs, and genes included in the phase-specific sigmulons. The number of genes included in the RpoS sigmulon was greater than in the RpoD sigmulon, with 1,833 and 1,690 genes included, respectively; however, a majority of sigmulon genes were found in all phase-specific sigmulons. Focussing on pathogenicity genes, 20 antimicrobial resistance genes (ARGs) and 155 virulence genes, only two ARGs were found exclusively in one phase-specific sigmulon, an oxacillin-hydrolysing class D beta-lactamase and chloramphenicol efflux MFS transporter CmlA5, which were found in the RpoD sigmulon in early stationary phase. Notably, six unnamed proteins that are or pertain to fimbrial proteins were found uniquely in the RpoS sigmulon in early stationary phase. From this, it can be hypothesised that early stationary phase might be an important phase for pathogenicity gene regulation. While there is little conservation in RpoS sigmulons from strain to strain, RpoS appears to have a consistent overarching role across strains, including a role as a regulator of pathogenicity genes.
Project description:Deciphering variable resistance to novel carbapenem-based beta-lactamase-inhibitor combinations and transmission pathways in a multiclonal outbreak by KPC carbapenemase-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam