«PemIK (PemK/PemI) type II TA system from Klebsiella pneumoniae clinical strains inhibits lytic phage»
Abstract Since their discovery, toxin-antitoxin systems have captivated many scientists. Recent studies demonstrated that a key role of TA systems is phage inhibition. Therefore, the aim of this study was to investigate the role of the PemIK (PemK/PemI) type II TA system in phage inhibition by its intrinsic expression in clinical strains of Klebsiella pneumoniae carrying OXA-48 carbapenemase and by induced its expression in an IPTG-inducible plasmid in a reference strain of K. pneumoniae ATCC®10031™. qRT-PCR revealed that pemK toxin in clinical strain ST16-OXA48 was induced when phage did not infect the strain, whereas when phage infection was successful pemK toxin was not induced. In addition, induced expression of the whole system did not inhibit phage infection, whereas overexpression of the pemK toxin prevented infection during the first hours. To investigate the molecular mechanism involved in the PemK toxin-mediated inhibition of phage infection, an assay measuring metabolic activity was performed, which revealed that production of toxin PemK led to the dormancy of the bacteria. Thus, we demonstrate that the PemK/PemI TA system plays a role in phage infection, and that the action of the free toxin causes the cells to go into a dormant state resulting in inhibition of phage infections.