NDM-1 - A Cause for Worldwide Concern

Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, USA.
New England Journal of Medicine (Impact Factor: 55.87). 12/2010; 363(25):2377-9. DOI: 10.1056/NEJMp1011715
Source: PubMed
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    • "[7] The New Delhi metallo beta-lactamse (NDM-1) is a novel type of MBL already has significant attention because of its association with extreme resistance, presence in common pathogens and the gene encoding this MBL is located on a mobile genetic element and its pattern of spreading is proving to be complex and unpredictable. [8] [9] After its first report in a Swedish patient of Indian origin, who had travelled to New Delhi in 2008, there was a fast spread of patients carrying bla NDM-1 gene [10] [11] [12] and now it has moved from India and Pakistan to the United Kingdom, Kenya, Japan, United States, Canada, Belgium, Netherlands, Taiwan, Singapore and Australia. [13] [14] [15] [16] "
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    • "As a prominent nosocomial pathogen it is mainly responsible for urinary tract, respiratory tract or blood infections [1-3]. In addition, because of the acquisition of extended-spectrum β-lactamases and carbapenemases, such as the recently described NDM-1 [4], multi, extremely or pan-drug resistant clinical strains are more frequently isolated [5,6]. In addition, K. pneumoniae has re-emerged as a cause of community-acquired infections including pneumonia and the characteristic syndrome of pyogenic liver abscess, with possible complications including endophthalmitis or meningitis [7,8]. "
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    ABSTRACT: Background Klebsiella pneumoniae strains are pathogenic to animals and humans, in which they are both a frequent cause of nosocomial infections and a re-emerging cause of severe community-acquired infections. K. pneumoniae isolates of the capsular serotype K2 are among the most virulent. In order to identify novel putative virulence factors that may account for the severity of K2 infections, the genome sequence of the K2 reference strain Kp52.145 was determined and compared to two K1 and K2 strains of low virulence and to the reference strains MGH 78578 and NTUH-K2044. Results In addition to diverse functions related to host colonization and virulence encoded in genomic regions common to the four strains, four genomic islands specific for Kp52.145 were identified. These regions encoded genes for the synthesis of colibactin toxin, a putative cytotoxin outer membrane protein, secretion systems, nucleases and eukaryotic-like proteins. In addition, an insertion within a type VI secretion system locus included sel1 domain containing proteins and a phospholipase D family protein (PLD1). The pld1 mutant was avirulent in a pneumonia model in mouse. The pld1 mRNA was expressed in vivo and the pld1 gene was associated with K. pneumoniae isolates from severe infections. Analysis of lipid composition of a defective E. coli strain complemented with pld1 suggests an involvement of PLD1 in cardiolipin metabolism. Conclusions Determination of the complete genome of the K2 reference strain identified several genomic islands comprising putative elements of pathogenicity. The role of PLD1 in pathogenesis was demonstrated for the first time and suggests that lipid metabolism is a novel virulence mechanism of K. pneumoniae.
    BMC Biology 05/2014; 12(1):41. DOI:10.1186/1741-7007-12-41 · 7.98 Impact Factor
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    • "Infections caused by K. pneumoniae can be difficult to treat since many clinical isolates possess an extensive repertoire of antibiotic resistance genes. Ominously, some strains have now been isolated from different parts of the world that harbor New Delhi metallo-β-lactamase 1 (NDM-1) [10,11], a gene that confers resistance to carbapenem antibiotics, the last-line treatment option against most K. pneumoniae infections. Compounding the medical threat is the paucity of new antibiotics that are being developed against multi-drug resistant Gram-negative bacteria such as K. pneumoniae. "
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    ABSTRACT: Klebsiella pneumoniae is a leading cause of hospital-acquired urinary tract infections and pneumonia worldwide, and is responsible for many cases of pyogenic liver abscess among diabetic patients in Asia. A defining characteristic of this pathogen is the presence of a thick, exterior capsule that has been reported to play a role in biofilm formation and to protect the organism from threats such antibiotics and host immune challenge. We constructed two knockout mutants of K. pneumoniae to investigate how perturbations to capsule biosynthesis alter the cellular phenotype. In the first mutant, we deleted the entire gene cluster responsible for biosynthesis of the extracellular polysaccharide capsule. In the second mutant, we deleted the capsule export subsystem within this cluster. We find that both knockout mutants have lower amounts of capsule but produce greater amounts of biofilm. Moreover, one of the two mutants abolishes fimbriae expression as well. These results are expected to provide insight into the interaction between capsule biosynthesis, biofilm formation, and fimbriae expression in this organism.
    BMC Research Notes 01/2014; 7(1):13. DOI:10.1186/1756-0500-7-13
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