Abstract:
OBJECTIVE To explore the multidrug resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae (CRKP), and analyze the association between the fosA6 gene and its mutations with fosfomycin resistance and phenotypic heterogeneity, with fosfomycin as an alternative therapeutic agent.
METHODS A total of 37 strains of CRKP were collected. The minimum inhibitory concentration (MIC) of fosfomycin against the strains was determined through the E-test method. The carriage and mutations of the fosA6 gene were analyzed through next-generation sequencing technology, and its correlation with MIC values was statistically analyzed.
RESULTS Among the 37 CRKP strains in the whole study, all carried the fosA6 gene. Among them, mutations in the fosA6 gene subtype were identified in 6 strains (including V57I, P60S, V91I, etc.). Phenotypic analysis showed that the fosfomycin MIC values (≤32 μg/ml) of strains carrying these mutations were significantly lower than those of non-mutated strains. There was a significant correlation between mutations in the fosA6 gene subtype and a decrease in fosfomycin MIC values (P < 0.05).
CONCLUSIONS The fosA6 gene is a core gene responsible for fosfomycin resistance in CRKP. Specific subtype mutations (V57I, P60S, V91I) can significantly weaken enzyme activity, leading to a decrease in drug resistance levels. This reveals the crucial role of "loss-of-function mutations" in resistance heterogeneity and provides a new perspective for clinical medication and resistance monitoring.
下载: