Photo Credit: David Dorward; Ph.D.; National Institute of Allergy and Infectious Diseases (NIAID) (2014)
Classical Klebsiella pneumoniae infection is thought of as causing opportunistic respiratory tract, urinary tract and healthcare associated infections. It is the most clinically relevant species in the genus Klebsiella and as with many other members of the family Enterobacteriaceae, both established and emerging antimicrobial resistant lineages have led to an increase in morbidity and mortality due to infection from these bacteria. Resistance to what is often last line of effective treatment, carbapenem antibiotics, mediated by a range of carbapenemases such as KPC, NDM, VIM and OXA-48-like1 has meant that carbapenem-resistant ESBL-producing Enterobacteriaceae including K. pneumoniae are classified as “Priority 1:Critical” on the WHO’s Priority Pathogens List for R&D of new antibiotics2. Over the past three decades a K. pneumoniae variant that causes invasive infectious disease (in contrast to the organism’s usual healthcare-associated epidemiology) has been gaining notoriety.
During the mid 1980s, reports of a distinctive syndrome characterised by community-acquired pyogenic liver abscess began to emerge from Taiwan3. Diabetes has been identified as a significant risk factor in host susceptibility, although infection was reported as occurring in otherwise healthy individuals. This syndrome has since been associated with accompanying bacteraemia, meningitis and brain abscess, and has had cases documented in Europe, North America, Australia and other parts of Asia4. Subsequent work has established that these invasive infections were predominantly caused by K. pneumoniae from a genetically similar background with a common set of conserved virulence factors; K. pneumoniae clonal group 23 (CG23), serotype K1.
The emergence of severe community-acquired disease caused by this hypervirulent Klebsiella pneumoniae (HvKp) pathotype is of significant public health concern. A deeper understanding of this pathogen is required, and the ability of clinicians and microbiologists to distinguish between classical K. pneumoniae disease and HvKp is of importance. Russo et al evaluated the accuracy of a range of tests to do this, with detection of peg-344, iroB, iucA, prmpA, and prmpA2 genes and quantitative siderophore production of ≥30µg highlighted as good predictors of HvKp5.
A comprehensive genomic study of CG23 has very recently been carried out by MMC Lam, KL Wyres et al6. Genomes were taken from 97 isolates originating from 18 countries and spanning a time period of more than 80 years from human and equine sources, including strains from the National Collection of Type Cultures and the Murray Collection. This analysis revealed a sub-lineage of CG23: CG23-I. CG23-I comprised 82% of human liver abscess isolates in the study, with the data suggesting that it emerged in human populations in approximately 1928 and has since expanded and is undergoing global dissemination. Insertion of genes that encode yersiniabactin and colibactin (an iron acquisition protein and genotoxin respectively) have contributed to the success of the CG23-I sub-lineage as a human pathogen. Acquisition of antimicrobial resistance (AMR) genes has so far been rare in human isolates.
MMC Lam, KL Wyres et al. makes apparent that the CG23-I sub-lineage is dominant in human HvKp infection. Of the current reference strains and genomes used to study HvKp, one (strain NTUH-K2044) does not belong to CG23-I and lacks colibactin while the other (strain 1084) lacks a virulence plasmid, and so neither are representative of the HvKp pathotype. Based on their findings the authors advocate the use of a more representative strain, SGH10, to support the work of public health authorities in HvKp surveillance and researchers in the investigation of emergence of stable AMR determinants in the CG23-I sub-lineage.
The SGH10 reference strain is available as NCTC 14052.
The annotated whole genome sequence is available through GenBank: accession numbers CP025080 (chromosome) and CP025081 (virulence plasmid).
Markers for the CG23-I sub-lineage can be detected from whole genome sequence data by using the Holt lab’s Kleborate tool or by conventional PCR7.
Written by Jake D. Turnbull
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