Antibiotic Induced Streptococcal Competence Do Not Always Correlate With Transformability

Objectives: Streptococcus pneumoniae and its oral relatives, Streptococcus mitis and Streptococcus mutans, are natural transforming species. Transformation occurs within a short competence window, during which extracellular DNA is uptaken and incorporated in their genomes. Subinhibitory concentrations of antibiotics may influence bacterial behavior in several ways, and some antibiotic agents are known to induce competence in S. pneumoniae. However, for most antibiotics it is unknown whether competence induction, assessed by expression of competence genes, is actually translated into increased transformation rates. The present study investigated whether subinhibitory concentrations of antibiotics induce competence and concurrently affect transformation in S. pneumoniae, S. mitis and S. mutans.
Methods: Seven antibiotics were examined for effects on streptococcal competence and transformability, by using luciferase reporters in wild-type backgrounds, RT-PCR, and high efficiency transformation protocols.
Results: Ciprofloxacin, novobiocin, erythromycin and tetracycline increased and prolonged the expression of sigX, encoding the master regulator of competence. However, the effect on transformation varied between the antibiotic agents. Ciprofloxacin and novobiocin prolonged, and slightly increased, transformation efficiency. Erythromycin did not have a significant effect on transformation, while tetracycline decreased the rate of transformation despite being the antibiotic agent with the highest sigX expression. Ampicillin, kanamycin and streptomycin inhibited competence. In S. mitis and S. mutans prolonged effects were observed both in sigX-expression and transformation rate in cultures treated with ciprofloxacin.
Conclusions: Antibiotics that stimulate competence may extend the time during which different streptococcal species undergo transformation by delaying exit from the competent state. For certain antibiotics, however, transformation may be inhibited despite competence induction, while for other antibiotics, competence is reduced. Understanding the effect of antibiotics on transformability is relevant, as it may influence the bacterial ability to acquire new traits, including antibiotic resistance.