The Potential Role of the Bacterial Persister Formation Gene ptsH in Hypervirulence Development in Klebsiella...

Persistence - i.e., the ability to exist in a metabolically inactive form - allows bacteria to accumulate genetic advantages. The evolution of the pathogenic potential of Klebsiella pneumoniae has led to the emergence of strains simultaneously characterized by increased aggressiveness (virulence) and prolonged survival in the host organism. This combination of properties contributes to the emergence of "superbugs," necessitating the search for specific markers that would make it possible to prevent the spread of highly adaptive clones. Hypervirulent K. pneumoniae (hvKp) strains represent a growing global health threat, since they combine high invasiveness and antibiotic resistance. An analysis of 92 K. pneumoniae clinical isolates was conducted to assess the prevalence of the key hypervirulence genes (iroB, peg-344, rmpA, rmpA2, and iucA) and investigate their association with the bacterial persister formation gene ptsH. It was found that 64.1% (59/92) of the isolates carried at least one hvKp gene, iucA being the most frequent one (62.0%). The full set of five hvKp genes was identified in only one case (1%). The strains of sequence types ST23, ST268, ST86, ST534, ST219, ST101, and ST395 accumulated virulence genes, whereas ST512 and ST14 rarely harbored hvKp genes. A key finding was the detection of a significant association between the presence of the ptsH gene (found in 50% of the strains) and the accumulation of hvKp genes: the ptsH-positive strains were statistically more likely to harbor the complete aerobactin operon (iucABCD), in combination with one or more additional hypervirulence genes, compared to the ptsH-negative strains (p < 0.05). Our findings indicate that the ptsH gene is crucial in the formation of polygenically determined hypervirulence, and that its role in controlling bacterial persistence creates evolutionary advantages under stress induced by antibiotics or immune factors, thus promoting evasion of their actions. The phosphotransferase system (PTS), to which the ptsH gene belongs, can potentially become a novel source of molecular targets for the therapy of infections caused by hypervirulent K. pneumoniae strains.