Oxidative stress response plays a role in antibiotic tolerance of Streptococcus mutans biofilms

• Main Authors: Nilsson, Martin, Jakobsen, Tim Holm, Givskov, Michael, Twetman, Svante, Tolker-Nielsen, Tim
• Other Authors: Singapore Centre for Environmental Life Sciences and Engineering
• Format: Article
• Language: English
• Published: 2021
• Subjects: Engineering::Bioengineering; Streptococcus Mutans; Biofilm
• Online Access: https://hdl.handle.net/10356/150228
• Institution: Nanyang Technological University

Knowledge about biofilm-associated antibiotic tolerance mechanisms is warranted in order to develop effective treatments against biofilm infections. We performed a screen of a Streptococcus mutans transposon mutant library for mutants with reduced biofilm-associated antimicrobial tolerance, and found that the spxA1 gene plays a role in tolerance towards gentamicin and other antibiotics such as vancomycin and linezolid. SpxA1 is a regulator of genes involved in the oxidative stress response in S. mutans. The oxidative stress response genes gor and ahpC were found to be up-regulated upon antibiotic treatment of S. mutans wild-type biofilms, but not spxA1 mutant biofilms. The gor gene product catalyses the formation of glutathione which functions as an important antioxidant during oxidative stress, and accordingly biofilm-associated antibiotic tolerance of the spxA1 mutant could be restored by exogenous addition of glutathione. Our results indicate that the oxidative stress response plays a role in biofilm-associated antibiotic tolerance of S. mutans, and add to the on-going debate on the role of reactive oxygen species in antibiotic mediated killing of bacteria.