Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection

Abstract

Background The key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive. Methods We analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded. Results We analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, using whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 (O1v1) clade was distinct from that of the K1-ST23 (O1v2) clone. The virulence gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition. However, the K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp. Conclusions The K1 genotype, rmpA, and aerobactin are prominent predictors of hvKp, suggesting that further pyogenic (metastatic) infection should be examined clinically. These findings may shed light on key hvKp virulence factors.

Epidemiological Features of Klebsiella pneumoniae Infection in the Hepatobiliary System of Patients in Yantai, China, Based on Clinical and Genetic Analyses

“…Moreover, hyperglycemia may inhibit the chemotaxis, adhesion and phagocytosis of white blood cells, as well as impairing intestinal barrier function and promoting the spread of K. pneumoniae . However, not all studies have reported this association, 14 , 15 and our results did not confirm this correlation, suggesting that the connection between diabetes and hvKP infection may vary by region or clinical presentation.…”

“… 8 HvKP strains have the capability to produce four different siderophores: enterobactin, salmochelin ( iro ), yersiniabactin ( ybt ) and aerobactin ( iuc ). 15 Aerobactin has been proven to be the primary virulence determinant that enables systemic infection, and salmochelin and aerobactin are hvKP-specific. 21 Peg-344 is a metabolic transporter of unknown function that has hvKP specificity.…”