LAUSR

Tigecycline resistance remains rare in S. aureus worldwide. Twelve TGC resistant S. aureus mutants (TRSAm) were obtained displaying an increase in their efflux activity. The isolates belonged to 7 different genetic lineages, with predominance of CC5. Diverse genetic changes in mepA and mepR genes were found producing alterations in the amino acid sequences of the corresponding proteins, MepA and MepR, respectively. The most frequent amino acid change in MepA was Glu287Gly. All the TRSAm exhibited different SNPs/INDELs in mepR causing premature stop codons or amino acid changes in MepR. The expression of mepA was significantly increased in TRSAm with different mutations in mepA and mepR. Six of twelve TRSAm also harbored mutations in rpsJ, which rendered amino acid changes in S10 ribosomal protein being Lys57 the most frequent mutated site. Our findings demonstrate that this acquired mechanism of TGC resistance is not restricted to a single type of genotypic background and that different lineages might have the same plasticity to develop TGC resistance. The impact of TGC selective pressure assessed by whole genome sequencing in 4 selected strain pairs revealed mutations in other singular genes and the IS256 mobilization.