Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43

Chen, Ying-Tsong; Chang, Hwan‐You; Lai, Yi-Ting; Pan, Chao; Tsai, Shih Feng; Peng, Hwei-Ling

doi:10.1016/j.gene.2004.05.008

Cited by 275 publications

(210 citation statements)

References 29 publications

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“…Several genetic loci have been identified as virulence factors in K. pneumoniae on the basis of murine models of infection. These include gene clusters associated with the synthesis of siderophore systems yersiniabactin, aerobactin, colibactin, salmochelin (40)(41)(42)(43), or microcin (44); the "regulators of mucoid phenotype" rmpA and rmpA2, which can up-regulate capsule production (45,46); an allantoinase gene cluster (47); the ferric uptake operon kfuABC (48); and the two-component regulator kvgAS (49). Most of these genes were detected only in KpI, except for kfuABC (found in all KpII-B, 75% of KpIII, and 20% of KpI) and allantoinase (found in 50% of KpII-B and 5% of KpI).…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae , an urgent threat to public health

Holt

Wertheim

Zadoks

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

960

1,078

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Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

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Section: Resultsmentioning

confidence: 99%

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae , an urgent threat to public health

Holt

Wertheim

Zadoks

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

960

1,078

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“…However, in all Enterobacteriaceae tested, virulence was significantly increased by the HPI (Bearden et al, 1997;Carniel et al, 1992;de Almeida et al, 1993;Lin et al, 2008;Schubert et al, 2002). Other genes associated with the EHOS were those previously described on the pLVPK virulence plasmid of K. pneumoniae CG43 (Chen et al, 2004). Also interesting were four DNA fragments encoding putative pili with the most homology to pili of the chaperone/usher pathway producing putative type 1 fimbriae from S. enterica.…”

Section: Discussionmentioning

confidence: 98%

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Paauw

Caspers²,

Hall

et al. 2009

Microbiology

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Bacterial strains differ in their ability to cause hospital outbreaks. Using comparative genomic hybridization, Enterobacter cloacae complex isolates were studied to identify genetic markers specific for Enterobacter cloacae complex outbreak strains. No outbreak-specific genes were found that were common in all investigated outbreak strains. Therefore, the aim of our study was to identify specific genetic markers for an Enterobacter hormaechei outbreak strain (EHOS) that caused a nationwide outbreak in The Netherlands. Most EHOS isolates carried a large conjugative plasmid (pQC) containing genes encoding heavy-metal resistance, mobile elements, pili-associated proteins and exported proteins as well as multiple-resistance genes. Furthermore, the chromosomally encoded high-pathogenicity island (HPI) was highly associated with the EHOS strain. In addition, other DNA fragments were identified that were associated with virulence: three DNA fragments known to be located on a virulence plasmid (pLVPK), as well as phage-and plasmid-related sequences. Also, four DNA fragments encoding putative pili with the most homology to pili of Salmonella enterica were associated with the EHOS. Finally, four DNA fragments encoding putative outer-membrane proteins were negatively associated with the EHOS. In conclusion, resistance and putative virulence genes were identified in the EHOS that may have contributed to increased epidemicity. The high number of genes detected in the EHOS that were related to transferable elements reflects the genomic plasticity of the E. cloacae complex and may explain the emergence of the EHOS in the hospital environment. INTRODUCTIONIn the pre-antibiotic era, isolates of the Enterobacter cloacae complex were not detected in surveys of nosocomial bacteria; they were first described as nosocomial pathogens in the 1970s (Sanders & Sanders, 1997). In 2001, Enterobacter spp. caused 7 % of nosocomial infections in intensive care units in the USA (Jones, 2003;Streit et al., 2004). Therefore, the E. cloacae complex can be considered as an emerging pathogen, of which Enterobacter hormaechei is the most commonly isolated nosocomial pathogen (Delmas et al., 2006;Paauw et al., 2008). A nationwide outbreak occurred with an E. hormaechei outbreak strain (EHOS) in The Netherlands . This strain disseminated throughout hospitals despite adequate implementation of internationally accepted infection-prevention guidelines and caused invasive infections in more than 100 patients (Paauw et al., 2007). Previous studies showed that most EHOS isolates carried the conjugative plasmid pQC, with several complex integrons containing aadB, bla CTX-M-9 and qnrA1 genes that encoded resistance to aminoglycosides and thirdgeneration cephalosporins, and reduced susceptibility to fluoroquinolones, respectively . However, it was also shown that other Enterobacteriaceae including other E. cloacae complex isolates with the pQC did not become highly epidemic like the EHOS (Paauw et al., 2007). Furthermore, of aminoglycoside-susceptible E. cloa...

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“…Additionally, the expression of several metal ion exporters, including two putative copper efflux transporters, CopA1 and CopA2, are induced in Legionella pneumophila upon phagocytosis by macrophages (40). Moreover, plasmids that increase the virulence of Klebsiella pneumoniae and Shigella sonnei harbor putative copper resistance genes (41,42).…”

Section: Discussionmentioning

confidence: 99%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

423

523

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Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-␥ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, suggesting a role for ATP7A-dependent copper transport in the bactericidal activity of macrophages. Significantly, a copper-sensitive mutant of Escherichia coli lacking the CopA copper-transporting ATPase was hypersensitive to killing by RAW264.7 macrophages, and this phenotype was dependent on ATP7A expression. Collectively, these data suggest that copper-transporting ATPases, CopA and ATP7A, in both bacteria and macrophage are unique determinants of bacteria survival and identify an unexpected role for copper at the hostpathogen interface.

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Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43

Cited by 275 publications

References 29 publications

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae , an urgent threat to public health

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae , an urgent threat to public health

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

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