Identification of a novel gene associated with group B Streptococcus persister cell formation and biofilm production

Antibiotic persistence arises when a subset of cells in an otherwise susceptible bacterial population temporarily exhibits elevated tolerance to bactericidal antibiotics. While significant progress has been made in elucidating persister mechanisms, much of this research has focused on Gram-negative bacteria, and these findings are not always applicable to Gram-positive species. This study explores genetic factors influencing persister cell formation in the Gram-positive Streptococcus agalactiae (Group B Streptococcus, GBS). The central finding in this study is the identification of the previously uncharacterized UvrD-like helicase homolog, gbs1341, as a factor affecting multidrug persistence and biofilm formation. Alongside gbs1341, mutants in relA and trmB were also found to be implicated. Mutations in these genes resulted in a phenotype characterized by elevated basal levels of the stringent response alarmone (p)ppGpp, linked with increased persister frequencies and enhanced biofilm production. In contrast, the gbs1341 deletion mutant displayed a significantly higher persister fraction following exposure to antibiotics, along with altered and enhanced biofilm formation, despite unaltered (p)ppGpp levels compared to the wild-type. These findings characterize gbs1341 as a novel genetic factor in both persister cell formation and biofilm production, highlighting a genetic link between these phenotypes, advancing our understanding of persistence in Gram-positive bacteria.