[UhpT mutation along with the presence of genes in the genome probably contributes to inherent fosfomycin resistance of ].

Objective: To investigate the molecular mechanism underlying inherent fosfomycin resistance of ().

Methods: The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes and and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of strains obtained from GenBank.

Results: All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpT mutation); the presence of gene was detected in 12 (85.71%) of the isolates and gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 strains from GenBank showed that 508 (97.50%) strains carried UhpT mutation, 439 (84.26%) strains harbored , and 80 (15.36%) strains harbored ; 507 (97.31%) strains were found to have both UhpT mutation and genes in the genome. Only 12 (2.30%) strains carried genes without UhpT mutation; 1 (0.19%) strain had only UhpT mutation without genes, and another strain contained neither UhpT mutation nor genes.

Conclusion: UhpT mutation with the presence of genes are ubiquitous in genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by , especially the multi-resistant HvKP/HmKP strains.