Project description:Background: Enterobacter cloacae complex (ECC) is a common opportunistic pathogen and is responsible for causing various infections in humans. Owing to its inducible chromosomal AmpC β-lactamase (AmpC), ECC is inherently resistant to the 1st- and 2nd- generation cephalosporins. However, whether β-lactams antibiotics enhance ECC resistance remains unclear. Results: In this study, we found that subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP) can advance the expression of AmpC and enhance its resistance towards β-lactams through NagZ in Enterobacter cloacae (EC). Further, AmpC manifested a substantial upregulation in EC in response to SICs of CFZ and IMP. In nagZ knockout EC (ΔnagZ), the resistance to β-lactam antibiotics was rather weakened and the effect of CFZ and IMP on AmpC induction was completely abrogated. NagZ ectopic expression can rescue the induction effects of CFZ and IMP on AmpC and increase ΔnagZ resistance. More importantly, CFZ and IMP have the potential to induce the expression of AmpR's target genes in a NagZ-dependent manner. Conclusions: Our findings suggest that NagZ is a critical determinant for CFZ and IMP to promote AmpC expression and resistance and that CFZ and IMP should be used with caution since they may aggravate ECC resistance. At the same time, this study further improves our understanding of resistance mechanisms in ECC.
Project description:Enterobacter cloacae is an important nosocomial pathogen. Here, we report the completion of the genome sequence of E. cloacae ATCC 13047, the type strain of E. cloacae subsp. cloacae. Multiple sets of virulence determinant and heavy-metal resistance genes have been found in the genome. To the best of our knowledge, this is the first complete genome sequence of the E. cloacae species.
Project description:Enterobacter cloacae subsp. cloacae strain ENHKU01 is a Gram-negative endophyte isolated from a diseased pepper (Capsicum annuum) plant in Hong Kong. This is the first complete genome sequence report of a plant-endophytic strain of E. cloacae subsp. cloacae.
Project description:Dissemination and characteristics of a novel carbapenem-hydrolysing class D β-lactamase, OXA-436 identified in different Enterobacteriaceae
Project description:We report draft genomes of Enterobacter cloacae strain S611, an endophytic bacterium isolated from surface-sterilized germinating wheat seeds. We present the assembly and annotation of its genome, which may provide insights into the metabolic pathways involved in adaptation.
Project description:Heteroresistance in bacteria describes a subpopulational phenomenon of transient antibiotic resistance variation among cells of a generally susceptible population. Here, we investigated the molecular mechanisms and phenotypic characteristics underlying heteroresistance to ceftazidime (CAZ) in a clinical Enterobacter cloacae complex strain (ECC). We identified a plasmid-borne gene duplication-amplification (GDA) event of a region harboring an ampC gene encoding a β-lactamase blaDHA-1 as the key determinant of heteroresistance. Individual colonies exhibited variations in the copy number of the genes resulting in resistance level variation which correlated with growth onset (lag times) and growth rates in the presence of CAZ, analysed in linear models. GDA copy number heterogeneity occurred within single resistant colonies, demonstrating heterogeneity of GDA on the single-cell level. The interdependence between GDA, lag time and antibiotic treatment and the strong plasticity underlying heteroresistance underlines the high risk for misdetection of antimicrobial heteroresistance and subsequent treatment failure.
Project description:The increasing spread of drug-resistant bacterial strains presents great challenges to clinical antibacterial treatment and public health, particularly with regard to β-lactamase-producing Enterobacteriaceae. A rapid and accurate detection method that can expedite precise clinical diagnosis and rational administration of antibiotics is urgently needed.
