Biological cost of fusidic acid resistance in Staphylococcus aureus

Abstract number: 902_p1721

Besier S.


Antibiotic resistance due to chromosomal mutations causing structural modifications in the cellular target of the drug is often associated with a fitness burden for the resistant bacteria. This loss of biological fitness, however, can be overcome in some cases by the acquisition of compensatory mutations. As shown recently, certain amino acid exchanges in elongation factor G (EF-G) of Staphylococcus aureus, such as H457Y, cause resistance to fusidic acid. Interestingly, fusidic acid-resistant clinical S. aureus isolates carrying the exchange H457Y frequently harbour additional amino acid substitutions within EF-G (e.g. S416F) which do not contribute to resistance. The aim of the present study was (i) to analyse the biological costs of the mutation H457Y and (ii) to investigate whether the mutation S416F is able to compensate for this fitness burden.


The influence of amino acid exchanges within EF-G on the biological fitness of S. aureus was analysed by measuring growth kinetics and by means of fitness assays and plasmacoagulase activity assays, using isogenic recombinant S. aureus strains carrying either the wild-type EF-G gene (fusA) or a mutant fusA derivative (H457Y, H457Y/S416F or S416F) on a multicopy plasmid. All assays started with a defined cell number of bacteria and were repeated three times to ensure reproducibility.


The assays showed that the fusidic acid resistance-mediating mutation H457Y causes a marked impairment of biological fitness. The amino acid exchange S416F, however, did not influence the fusidic acid susceptibility and impaired the biological fitness of the bacteria only slightly when present individually. The strain expressing the EF-G derivative with the double mutation H457Y/S416F, however, grew significantly faster, showed enhanced fitness in competition with the wild-type and exhibited a higher plasmacoagulase activity than the strain harbouring the single exchange H457Y.


The presented data provide evidence that the amino acid exchange S416F in EF-G functions as a fitness-compensating mutation in fusidic acid-resistant S. aureus harbouring the EF-G mutation H457Y, thereby demonstrating that the biological cost of fusidic acid resistance in S. aureus can be considerably reduced by secondary mutations within the bacterial genome.


Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Location: Oxford, UK
Presentation type:
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