Download Identification of Biochemical Differences on Fusidc acid resistant

How Do the Fusidic Acid Resistant Strains of Staphylococcus aureus Gain
Fitness to Survive?
Hasanthi Karunasekera
Staphylococus aureus is a naturally occurring bacterium causing a wide range of illnesses from
skin infections to life threatening diseases such as pneumonia and meningitis. Fusidic acid is one
of the most effective antibiotics used till date for the treatment of severe Staphylococus aureus
infections, while most of the other antibiotics have failed due to development of resistant strains.
Fusidic acid controls bacterial growth by inhibiting its protein synthesis. Resistance against
fusidic acid is mainly due to mutations in the fus A gene. Like other antibiotics fusidic acid
resistance is also associated with the fitness of resistant bacteria, resulting in reduced growth, low
virulence and poor survival. In order to overcome this, some bacterial strains have developed
additional mutations (fitness compensatory mutations) that result in better growth and survival
and become similar to the wild type strains (non-resistant).
In this study, I have chosen some naturally occurring fusidic acid resistant strains of the grampositive bacterium Staphylococcus aureus having one or more mutations. The main mutation
responsible for fusidic acid resistance is called primary mutation and the other mutations
responsible for improving fitness are called secondary mutations or fitness compensatory
mutations, which are usually present together with the primary mutation. My aim was to
understand why the primary mutants are physiologically unfit and how the secondary mutants
become more fit.
Experiments were carried out to test how well the antibiotic fusidic acid could act on these
mutants in comparison to the wild-type S. aureus
From the results it was found that all mutants (used in this study) conferring fusidic acid
resistance were very poor binders of fusidic acid. But the fitness compensatory mutations showed
higher activity than those with only primary mutation in tRNA translocation. Therefore I
conclude that the fusidic acid resistance in these strains is caused by the primary mutation, and
the gained ability of tRNA translocation in the secondary mutants must be due to the secondary
or fitness compensatory mutations. I don’t know yet how these mutations have gained the ability
in protein synthesis. I leave this question open for future investigations.
Degree project in Biology
Examenarbete i biologi, 20 p, spring 2007
Biology Education Centre, Department of Molecular Cell Biology, Uppsala University
Supervisor: Suparna Sanyal