Abstract
BackgroundKlebsiella 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.ResultsIn 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.ConclusionsDetermination 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.
Highlights
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
In order to identify new K. pneumoniae K2 virulence factors, we sequenced the genome of the virulent strain Kp52.145, as well as two additional strains of low virulence, SB2390 and SB3193. By comparing these three novel genomes to the publicly available genomes of the virulent K1 strain NTUH-K2044 and reference strain MGH 78578, we identified in Kp52.145 putative virulence genes and analyzed their distribution within a diverse collection of K. pneumoniae strains
Finishing efforts resulted in the complete genome sequence of K. pneumoniae Kp52.145, comprising 5.45 Mbp and 5,314 protein coding genes (Figure 1)
Summary
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. 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. Reference strain Kp52.145 (derived from B5055, the reference strain of serotype K2) is a highly virulent strain from which important virulence factors, including the large virulence plasmid harboring the regulator of mucoid phenotype (rmpA) and the aerobactin cluster, were identified [10,11,21]. Known virulence factors are certainly crucial for bacterial survival, protection and interaction with the host, putative new virulence factors that could subvert host cell physiology and response remain yet to be identified
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