In vitro selection of Staphylococcus aureus mutants resistant to tigecycline with intermediate susceptibility to vancomycin

Abstract

BackgroundTigecycline (TIG) is an antibiotic belonging to the glycylcyclines class and appears to be a good choice to fight infections caused by Staphylococcus aureus. To date, TIG exhibits good activity against this microorganism. The aim of this work was to obtain in vitro mutants of S. aureus resistant to TIG and evaluate possible changes in their susceptibility patterns to other antibiotics.ResultsTwo mutants of S. aureus resistant to TIG (MIC = 16 µg/mL) were selected in vitro from clinical isolates of methicillin-resistant S. aureus. In both mutants, corresponding to different lineage (ST5 and ST239), an increase of efflux activity against TIG was detected. One mutant also showed a reduced susceptibility to vancomycin, corresponding to the VISA phenotype (MIC = 4 µg/mL), with a loss of functionality of the agr locus. The emergence of the VISA phenotype was accompanied by an increase in oxacillin and cefoxitin MICs.ConclusionsThis study demonstrates that, under selective pressure, the increase of efflux activity in S. aureus is one of the mechanisms that may be involved in the emergence of tigecycline resistance. The emergence of this phenotype may eventually be associated to changes in susceptibility to other antibiotics such oxacillin and vancomycin.

Efflux Pump Overexpression Contributes to Tigecycline Heteroresistance in Salmonella enterica serovar Typhimurium

“…This occurrence is of great concern because of the greater probability to induce cross-resistance to new antibiotics with the application of empirical therapies. Overexpression of efflux pump can also lead to tigecycline resistance in S. aureus and, furthermore, that the acquisition of this resistance may be associated with reduced susceptibility to vancomycin (Herrera et al, 2016 ). After addition of PAβN, reduction of MIC values was observed for all resistant isolates that indirectly proves that efflux pump over-expression contributed to reduced tigecycline susceptibility.…”

Knowledge of Zika and perception of risk among sexually-active adults in the United States of America: results from a nationally representative sample

“…ZIKV presents multiple forms of transmission: through the bite of an infected Aedes aegypti mosquito; through sexual intercourse; and from mother-to-child in-utero (2 – 6). ZIKV infection has been linked to increased cases of microcephaly and other types of cognitive impairment in infants (7 – 9).…”

First description of rpsJ and mepA mutations associated with tigecycline resistance in Staphylococcus aureus isolated from a cystic fibrosis patient during antibiotic therapy

“…Minimum inhibitory concentration (MIC) results were interpreted based on 2017 European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (resistance, >0.5 μg/mL) (http://www.eucast.org). Quality controls were performed using S. aureus ATCC 29213 (susceptible strain, MIC = 0.064 μg/mL) and S. aureus 94159m, an in vitroselected TGC-non-susceptible mutant (MIC = 16 μg/mL) [3].…”