Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance

Abstract

Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.

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

“…This is consistent with numerous reports of K. pneumoniae strains carrying multiple AMR plasmids; e.g. the ST11 reference genome, HS11286, harbours six plasmids (1.3--123 kbp in size), three of which carry AMR genes [79]; and there are many examples in other lineages [10,80,81]. Its elevated plasmid load (Fig 2B) suggests K. pneumoniae is particularly permissive for plasmids, meaning it may be more likely to capture plasmid--borne material from diverse donors in varied niches, and to hold on to this material long enough to transmit it to new recipients in human and animal--associated niches (Fig 4).…”

“…The vast majority of AMR genes in K. pneumoniae are plasmid--borne [10,12], hence the ability to amplify and spread AMR genes across ecological niches is likely linked to plasmid--permissive traits. Highly diverse environmental microbial communities, especially soils, are considered hotspots for gene transfer [76], and Enterobacteriaceae have been identified as a component of the "super--permissive community" that supports the spread of plasmids across diverse soil communities [77].…”

“…Highly diverse environmental microbial communities, especially soils, are considered hotspots for gene transfer [76], and Enterobacteriaceae have been identified as a component of the "super--permissive community" that supports the spread of plasmids across diverse soil communities [77]. The specific role of K. pneumoniae in such activities remains to be explored, however the species has been associated with hundreds of distinct plasmids spanning many plasmid replicon types [9,10,13,78], which suggests it acts as a recipient for plasmids originating from a wide array of HGT donors. The median number of plasmids per complete K. pneumoniae genome currently in NCBI GenBank is three (interquartile range, 2--5; range 0--10), significantly higher than that for the other species of interest (p<1x10 --5 , see Fig 2B).…”

“…It is has recently been shown that some chromosomal adaptations (such as helicase and RNA polymerase mutations) can increase general plasmid permissiveness of a host bacterium [85]. Intriguingly, it is clear that AMR genes and plasmids are not randomly distributed amongst K. pneumoniae lineages [9,10], suggesting that there may be significant variation in plasmid permissiveness between lineages. Related species and strains can vary substantially in their ability to act as plasmid donors [77,86], however variation in plasmid--donor potential between K. pneumoniae and other bacteria, or between strains of K. pneumoniae, remains to be investigated.…”

Occurrence of the mcr-1 Colistin Resistance Gene and other Clinically Relevant Antibiotic Resistance Genes in Microbial Populations at Different Municipal Wastewater Treatment Plants in Germany

“…The combination of high cell densities in activated sludge tanks, increased nutrient availability, co-selections by heavy metals and selective pressures like complex mixtures of low-concentrated xenobiotics (e.g., antibiotics, biocids, disinfectants, pharmaceuticals) is hypothesized to promote horizontal gene transfer and therefore the persistence of certain antibiotic resistant bacteria in wastewater environments (Rizzo et al, 2013; Berendonk et al, 2015). This is of major concern because it has been shown, that some human pathogens are involved in high rates of horizontal gene transfer like K. pneumoniae (Hu et al, 2016; Navon-Venezia et al, 2017) and could enhance the dissemination of the mcr-1 plasmid. Potential mcr-1 carrying opportunistic pathogens, i.e., A. baumannii, E. coli , and K. pneumoniae were quantified in higher abundances even at effluent sampling sites.…”