Abstract
Klebsiella pneumoniae is a human pathogen, prominent in antimicrobial-resistant and nosocomial infection. The integrative and conjugative element ICEKp1 is present in a third of clinical isolates and more prevalent in invasive disease; it provides genetic diversity and enables the spread of virulence-associated genes. We report a second integrative conjugative element that can co-occur with ICEKp1 in K. pneumoniae. This element, ICEKp2, is similar to the Pseudomonas aeruginosa pathogenicity island PAPI. We identified ICEKp2 in K. pneumoniae sequence types ST11, ST258 and ST512, which are associated with carbapenem-resistant outbreaks in China and the US, including isolates with and without ICEKp1. ICEKp2 was competent for excision, but self-mobilisation to recipient Escherichia coli was not detected. In an isolate with both elements, ICEKp2 positively influenced the efficiency of plasmid mobilisation driven by ICEKp1. We propose a putative mechanism, in which a Mob2 ATPase of ICEKp2 may contribute to the ICEKp1 conjugation machinery. Supporting this mechanism, mob2, but not a variant with mutations in the ATPase motif, restored transfer efficiency to an ICEKp2 knockout. This is the first demonstration of the interaction between integrative and conjugative genetic elements in a single Gram-negative bacterium with implications for understanding evolution by horizontal gene transfer.
Highlights
Klebsiella pneumoniae is an important pathogen contributing to nosocomial and antimicrobial resistant infections
The evidence we present of cross-talk between integrative and conjugative elements (ICEs) is Mob2-mediated increase in the efficiency of ICEKp1-driven plasmid mobilisation
ICEKp2 is highly related to Pseudomonas Pseudomonas aeruginosa pathogenicity island family (PAPI), which is more widespread in Pseudomonas than in Enterobacteriaceae
Summary
Klebsiella pneumoniae is an important pathogen contributing to nosocomial and antimicrobial resistant infections. The acquisition and spread of antimicrobial resistance-associated and virulence-associated genes is facilitated by certain types of mobile genetic element (MGE) including plasmids, insertion sequences, transposons, integrons and associated gene cassettes, prophages, self-transmissible integrative and conjugative elements (ICEs) and genomic islands[6,7]. K. pneumoniae carries many MGE, two of which have been linked to virulence: ICEKp1, a 62 kb chromosomal island integrated at tRNAasn, and plasmid pLVPK. These elements are more prevalent in invasive disease isolates, and pLVPK influences capsule type[1,8]. A PAPI-like element was reported in E. coli BEN374 (ICEEc2) and shown to be capable of excision, though mobilisation remains incompletely characterised[20]. To determine the evolutionary and functional relationship between the newly annotated PAPI-like ICEKp2 and the more widespread ICEKp1, we undertook annotation and functional characterisation of ICEKp2 to determine its potential for self-mobilisation, DNA mobilisation in trans, and influence on DNA mobilisation by ICEKp1
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