pneumoniae strains that infect

otherwise healthy individuals have emerged from initial endemic foci in Taiwan and China, and are now spreading into North America and Europe [4–6]. This highlights the increasing threat that K. pneumoniae poses to public health and the importance of elucidating its mechanisms of pathogenesis. Most K. pneumoniae strains possess a thick polysaccharide capsule which is involved in protection from opsonisation and phagocytosis and is a well recognized in vivo virulence factor [7]. HDAC activation Various studies have also highlighted roles for surface-exposed lipopolysaccharides, multiple iron acquisition systems and adhesins in K. pneumoniae infection [1, 7, 8]. Several strain-specific virulence determinants of the pyogenic liver abscess-associated

this website isolate K. pneumoniae NTUH-K2044 have been well characterised [9–11]. However, the functions of strain-specific genomic regions in K. pneumoniae strains associated with other types of infection remain poorly studied. Comparative analyses using computational and in vitro experimental techniques have shown that K. pneumoniae strains possess an extremely plastic genome that consists of a conserved core genome interspersed by strain-specific accessory components [12–15]. This was further highlighted in a recent study which calculated that only 54.7% of known K. pneumoniae genes were shared by three sequenced isolates (Kp342, MGH78578, NTUH-K2044) [15]. Genomic islands (GI), typically ranging from 10 kb to 200 kb in size and frequently inserted

within tRNA gene (tRNA) hotspots, comprise a substantial proportion of the accessory genome. GI acquisition offers an efficient ‘quantum leap’ based route to gaining virulence factors, antibiotic resistance determinants and/or metabolic pathways pre-tailored for the exploitation of new environments [16, 17]. Epidemiological studies have suggested that K. pneumoniae infections are preceded by Phosphoglycerate kinase colonization of the gastrointestinal tract [18]. Adhesion and colonization are essential steps in the infection process and are often mediated by fimbriae, which are small hair-like extensions on the bacterial cell surface that can interact with other surfaces via tip-located adhesin proteins [19]. The majority of environmental and clinical K. pneumoniae isolates are known to express type 1 fimbriae and type 3 fimbriae, which have recently been classified into the γ1 and γ4-fimbrial subgroups using the Nuccio and Bäumler fimbrial classification system, which was created from a large scale phylogenetic analysis of fimbrial usher proteins [20–23]. Recent in vivo experiments have demonstrated a role for K. pneumoniae type 1 fimbriae in urinary tract infections [22].