ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae , co-occurring and interacting with ICEKp1

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.