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Published on: September 3, 2016
Sub-growth-inhibitory concentrations of omadacycline inhibit Staphylococcus aureus haemolytic activity in vitro
Alisa W Serio1, S Ken Tanaka1, Kelly Wright1
1Paratek Pharmaceuticals, Inc., 1000 First Ave, Suite 200, King of Prussia, PA 19406, USA.
Objectives:
To evaluate the effect of sub-growth-inhibitory concentrations of omadacycline on Staphylococcus aureus ATCC 10832 haemolytic activity in vitro.
Methods:
Following determination of the MICs of omadacycline and comparator antibiotics, the strain was grown in the presence of individual antibiotics and the percentage of haemolysis assayed; 'washout' experiments were performed with omadacycline only.
Results:
Omadacycline inhibited S. aureus haemolytic activity in vitro at sub-growth-inhibitory concentrations. Inhibition was maintained at least 4 h after removal of extracellular drug.
Conclusions:
Omadacycline's in vitro potency and suppression of virulence factors might contribute to its efficacy in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia caused by virulent strains of S. aureus. This finding could be relevant for other organisms and virulence factors that depend on new protein synthesis.
Insights
Omadacycline effectively reduced Staphylococcus aureus haemolytic activity in vitro at concentrations below those that inhibit growth. This virulence suppression persisted even after the antibiotic was removed.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Staphylococcus aureus is a significant human pathogen.
- Virulence factors, such as haemolysin, contribute to S. aureus pathogenicity.
- Novel therapeutic strategies are needed to combat S. aureus infections.
Purpose of the Study:
- To investigate the impact of sub-growth-inhibitory concentrations of omadacycline on Staphylococcus aureus haemolytic activity.
- To assess the duration of omadacycline's effect on haemolysis after drug removal.
Main Methods:
- Minimum inhibitory concentrations (MICs) of omadacycline and comparator antibiotics were determined.
- S. aureus was cultured with sub-inhibitory antibiotic concentrations, and haemolysis was quantified.
- 'Washout' experiments were conducted to evaluate the persistence of omadacycline's effect.
Main Results:
- Omadacycline demonstrated significant inhibition of S. aureus haemolytic activity at sub-growth-inhibitory concentrations in vitro.
- The inhibitory effect on haemolysis was sustained for at least 4 hours post-antibiotic removal.
- This suggests a non-lethal mechanism of virulence factor suppression.
Conclusions:
- Omadacycline exhibits in vitro potency in suppressing S. aureus virulence factors.
- This suppression of haemolytic activity may contribute to omadacycline's clinical efficacy against S. aureus infections.
- The findings suggest potential applications for omadacycline against other pathogens and virulence factors dependent on de novo protein synthesis.
