Tigecycline is regarded as one of the few important last-resort
antibiotics to treat complicated skin and
intra-abdominal infections. Members of the genus Staphylococcus are zoonotic pathogens and pose a serious threat to public health.
Tigecycline resistance in this species appears to be a rare phenomenon, and the mechanisms underlying
tigecycline resistance have not been fully elucidated. Here, we report two novel variants of the tet(L) gene in Staphylococcus spp. from swine in China, designed as tet(L)F58L and tet(L)A117V. The tet(L)F58L was located within a 18,720 bp chromosomal multidrug resistance gene cluster flanked by two copies of IS257 in Staphylococcus cohnii 11-B-312, while the tet(L)A117V was located on a 6,292 bp plasmid in S. haemolyticus 11-B-93, which could be transferred to S. aureus by electrotransformation. Cloning of each of the two tet(L) variants into S. aureus RN4220 showed 16- or 8-fold increases in the minimal inhibition concentrations (MICs), which can fully confer the resistance to
tigecycline (MICs from 0.125 to 2 mg/liter) and
eravacycline (MICs from 0.125 to 1 or 2 mg/liter), but no increase in the MICs of
omadacycline, compared with the MICs of the recipient strain S. aureus RN4220. In the in vivo murine
sepsis and in the murine
pneumonia models, an increase in CFU of S. aureus 29213_pT93 carrying the tet(L)A117V was seen despite
tigecycline treatment. This observation suggests that the tet(L)A117V and its associated gene product compromise the efficacy of
tigecycline treatment in vivo and may lead to clinical treatment failure. Our finding, that novel Tet(L) efflux pump variants which confer
tigecycline and
eravacycline resistance have been identified in Staphylococcus spp., requires urgent attention. IMPORTANCE
Tigecycline and
eravacycline are both important last-resort broad spectrum
antimicrobial agents. The presence of novel Tet(L) efflux pump variants conferring the resistance to
tigecycline and
eravacycline in Staphylococcus spp. and its potential transmission to S. aureus will compromise the efficacy of
tigecycline and
eravacycline treatment for S. aureus associated
infection in vivo and may lead to clinical treatment failure.