Background:
Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 700 million human infections annually worldwide. β-lactam antibiotics are the primary agents used to treat GAS infections. In recent years, GAS clinical isolates with decreased susceptibility to β-lactam antibiotics have been documented. This prompted us to investigate GAS genes affecting penicillin susceptibility on a genome-wide scale.
Methods:
Here, using saturated transposon mutagenesis, we screened for GAS gene mutations (transposon insertion inactivation) conferring decreased in vitro susceptibility to penicillin G, a β-lactam antibiotic commonly used to treat GAS infections.
Results:
We found insertion inactivation of 15 GAS genes is associated with decreased susceptibility to penicillin G in vitro. Many of these identified genes are previously unknown to alter β-lactam susceptibility or affect cell wall biosynthesis. Using isolated individual transposon insertion mutant strains, we confirmed that inactivation of three genes resulted in decreased in vitro susceptibility to penicillin G.
Conclusions:
Our genetic screen identified novel gene mutations affecting GAS susceptibility to penicillin. These results provide new information about the molecular mechanisms of GAS-penicillin interaction and bacterial cell-wall homeostasis.