Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae

Abstract

Multidrug resistant and hypervirulent clones of Klebsiella pneumoniae are emerging pathogens. To understand the association between genotypic and phenotypic diversity in this process, we combined genomic, phylogenomic and phenotypic analysis of a diverse set of K. pneumoniae and closely related species. These species were able to use an unusually large panel of metabolic substrates for growth, many of which were shared between all strains. We analysed the substrates used by only a fraction of the strains, identified some of their genetic basis, and found that many could not be explained by the phylogeny of the strains. Puzzlingly, few traits were associated with the ecological origin of the strains. One noticeable exception was the ability to use D-arabinose, which was much more frequent in hypervirulent strains. The broad carbon and nitrogen core metabolism of K. pneumoniae might contribute to its ability to thrive in diverse environments. Accordingly, even the hypervirulent and multidrug resistant clones have the metabolic signature of ubiquitous bacteria. The apparent few metabolic differences between hypervirulent, multi-resistant and environmental strains may favour the emergence of dual-risk strains that combine resistance and hypervirulence.

The ZKIR Assay, a novel Real-Time PCR Method for the Detection of Klebsiella pneumoniae and Closely Related Species in Environmental Samples

“…These results contrast with clinical and animal isolates, where plasmids and metal tolerance clusters are common (42, Rodrigues, unpublished results). As expected (1, 36), all Kp3 isolates harbored the nif cluster responsible for nitrogen fixation. Interestingly, the nif cluster was also present in one Kp1 isolate from soil (SB6181).…”

“…Interestingly, the nif cluster was also present in one Kp1 isolate from soil (SB6181). The phylogenetic analysis ( Figure S2 ) of the nif cluster from our environmental isolates compared to a panel of reference strains (36) revealed that strain SB6181 (Kp1) branched within K. variicola strains (Kp3), showing that the nif cluster in this Kp1 strain was acquired via horizontal gene transfer from a K. variicola donor. Kp3 was also the inferred donor of the nif gene cluster for Kp5 and Kp6 nif -positive strains (Figure S2).…”

“…PlasmidFinder was used to look for plasmid replicons (https://cge.cbs.dtu.dk/services/PlasmidFinder/). To construct the tree based on nif cluster genes ( Figure S2 ), the DNA region between nifQ and nifJ genes was extracted from the nif carrying strains and from a set of reference strains carrying this cluster (36). Sequences were aligned with MUSCLE, and IQ-TREE (http://iqtree.cibiv.univie.ac.at) was used to reconstruct the maximum likelihood phylogeny using the HKY+I+F+G4 model.…”

Population genomics of hypervirulentKlebsiella pneumoniaeclonal group 23 reveals early emergence and rapid global dissemination

“…A recent metabolic study of Kp growth under aerobic conditions included two ST23 strains NTUH-K2044 (intact eat) and SB4385 (CG23-I, disrupted eat). Both grew on ethanolamine with no apparent differences in efficiency 58 , indicating no detrimental effect of the loss of Eat in CG23-I strains during aerobic growth, hence the available evidence indicates this change is unlikely to be of particular functional significance to the lineage.…”

Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria

“…A substantial proportion of the total pan--genome (core + accessory genes, [66]) is predicted to encode proteins with metabolic functions; 19% associated with carbohydrate metabolism, 18% with other metabolic pathways and 13% with membrane transport [9]. This extensive diversity results in variable metabolic capacity [67], potentially supplementing individual strains with additional ecological range and providing even more opportunities for genetic exchange. Direct comparison of population structures are difficult due to different sampling and analysis strategies [66]; nonetheless it is clear that the other Gram negative opportunists also have many deep branching lineages and large pan--genomes [9,[68][69][70][71].…”