Abstract
The Klebsiella pneumoniae species complex includes important opportunistic pathogens which have become public health priorities linked to major hospital outbreaks and the recent emergence of multidrug-resistant hypervirulent strains. Bacterial virulence and the spread of multidrug resistance have previously been linked to toxin–antitoxin (TA) systems. TA systems encode a toxin that disrupts essential cellular processes, and a cognate antitoxin which counteracts this activity. Whilst associated with the maintenance of plasmids, they also act in bacterial immunity and antibiotic tolerance. However, the evolutionary dynamics and distribution of TA systems in clinical pathogens are not well understood. Here, we present a comprehensive survey and description of the diversity of TA systems in 259 clinically relevant genomes of K. pneumoniae. We show that TA systems are highly prevalent with a median of 20 loci per strain. Importantly, these toxins differ substantially in their distribution patterns and in their range of cognate antitoxins. Classification along these properties suggests different roles of TA systems and highlights the association and co-evolution of toxins and antitoxins.
Highlights
The Klebsiella pneumoniae species complex, which includes K. pneumoniae sensu stricto, K.quasipneumoniae and K. variicola, is a major threat to public health
Type II and type IV TA systems are highly abundant in the K. pneumoniae species complex
Four additional species from this complex have been described [57,58,59], our study focuses on these three species as there is a well described dataset consisting of these species that reflects the clinically relevant diversity of the K. pneumoniae species complex [31]
Summary
The Klebsiella pneumoniae species complex, which includes K. pneumoniae sensu stricto, K.quasipneumoniae and K. variicola, is a major threat to public health. Of particular concern is the recent emergence of convergent multidrug-resistant and hypervirulent strains; these two phenotypes, both carried on mobile elements, were so far considered mutually exclusive. These new strains cause serious community-acquired infections in otherwise healthy individuals with few treatment options given their extensive drug resistance profiles [5,6,7,8,9]. TA systems were first discovered as loci that enforce the maintenance of plasmids via post-segregational killing [13] They are comprised of bicistronic operons encoding a toxin which inhibits cellular processes such as translation or DNA replication and an antitoxin which counteracts the toxins’
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