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. 2016 Mar 8:15:15.
doi: 10.1186/s12941-016-0131-7.

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

Melina Herrera  1 , Sabrina Di Gregorio  2 , Silvina Fernandez  3 , Graciela Posse  4 , Marta Mollerach  5 , José Di Conza  6   7   8
Affiliations

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

Melina Herrera et al. Ann Clin Microbiol Antimicrob. .

Abstract

Background: Tigecycline (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.

Results: Two 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.

Conclusions: This 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.

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Figures

Fig. 1
Fig. 1
SmaI-PFGE of the parental and mutant strains. Lane 1: parental strain 2028p, lane 2: mutant strain 2028 m, lane 3: parental strain 94159p, lane 4: mutant strain 94159 m
Fig. 2
Fig. 2
δ-Hemolysin assays. The strain streaked vertically is β-hemolysin-producing RN4220. Strain N315 was used as a negative control. a A zone of enhanced hemolysis by strain 94159p is seen as an arrowhead (δ-hemolysin); the δ-hemolytic capacity has been lost by strain 94159 m. b Strains 2028p and 2028 m both produce β- and δ-hemolysins
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