Tracking microevolution events among ST11 carbapenemase-producing hypervirulent Klebsiella pneumoniae outbreak strains

Figures & data

List of chromosomal SNP differences among the clonal CR-hvKP outbreak strains tested

Position in reference	CR-HvKP1 (Reference)	CR-HvKP4	CR-HvKP5	Product	Effect with DNA (c.) and protein (p.) changes
53198	A	G	G	–
547060	A	C	C	Lipoprotein nlpI precursor	Missense variant; c.115 A > C p.Lys39Gln
621416	A	A	T	Phosphoenolpyruvate-dihydroxyacetone phosphotransferase (EC 2.7.1.121), subunit DhaM	Missense_variant; c.992 T > A p.Val331Asp
769687	A	C	C	Antirestriction protein	Stop_lost & splice_region_variant; c.740 A > C p.Ter247Serext*?
1781309	A	C	C	–
1783244	A	C	C	–
2179080	T	T	G	–
4604288	G	T	G	Hypothetical protein	Missense variant; c.76 C > A p. Gln26Lys
4766271	A	G	A	–
4766275	G	A	G	–
4766278	G	A	G	–
4767184	G	A	G	–
4767185	A	G	A	–

Nucleotide and amino acid changes in DNA and protein sequences of K. pneumoniae strains CR-HvKP4 and CR-HvKP5, with reference to the K. pneumoniae CR-HvKP1 chromosome sequence; The symbol ‘–’ in the column “product” represents non-coding regions in the sequence

Fig. 1 Comparison of the ST11 CR-hvKP genomes.

Major regions of divergence are labeled, including: (1) An 1.5-Kb deletion in the K. pneumoniae 4 genome with two genes encoding hypothetical proteins (indicated with a black arrow); (2) disruption of the mgrB gene by insertion sequence (ISKpn18) in the K. pneumoniae 5 genome (indicated with a black arrow); (3) A 16.5-Kb region of the K. pneumoniae 5 genome (indicated by a blue rectangle) is absent in the other two ST11 K. pneumoniae genomes. Predicted genes within this region are indicated: (a) peptidase; (b) fatty acid desaturase; (c) phosphate ABC transporter substrate-binding protein; (d) nitrilotriacetate monooxygenase; (e) hypothetical protein; (f) transcriptional regulator TdcA; (g) bifunctional threonine ammonia-lyase/L-serine ammonia-lyase TdcB; (h) threonine/serine transporter TdcC; (i) propionate kinase; (j) formate C-acetyltransferase; (k) branched-chain amino acid ABC transporter substrate-binding protein; (l) branched-chain amino acid ABC transporter permease, LivH; (m) branched-chain amino acid ABC transporter permease, LivM; (n) ABC transporter ATP-binding protein, LivG; (o) ABC transporter ATP-binding protein, LivF

Fig. 2 Schematic representation of the two insertion events that occurred in the mgrB gene.

The mgrB gene was truncated by ISKpn18 in both K. pneumoniae 5 (a) and K. pneumoniae 3 (b) strains with opposite directions at different positions. Target site duplications are underlined with bold letters. The left and right inverted repeats (IRL and IRR) of ISKpn18 are represented as black triangles

Fig. 3 Plasmids from the ST11 CR-hvKP isolates.

Each of the three ST11 isolates carried five plasmids, with sizes of 178, 177.5, 99.7, 11.9, and 5.6 Kb. Insertion sequences and antimicrobial resistance genes are annotated with blue and yellow fonts, respectively. Plasmid name, size, and replicon types are depicted in the middle of each circle. The 11.4-Kb homologous region (HR) in the virulence plasmid and MDR plasmid, and 4.5-Kb region of divergence (RD) in the 99.7-Kb plasmid are highlighted