Bacterial biofilms are responsible for a variety of serious human
infections and are notoriously difficult to treat due to their recalcitrance to
antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this
antibiotic tolerance. The
arginine deiminase (ADI) pathway is responsible for bacterial pH maintenance and is highly expressed during biofilm growth in multiple bacterial species. Using the group A Streptococcus (GAS) as a model human pathogen, the ADI pathway was demonstrated to contribute to biofilm growth. The inability of
antibiotics to reduce GAS populations when in a biofilm was demonstrated by in vitro studies and a novel animal model of nasopharyngeal
infection. However, disruption of the ADI pathway returned GAS biofilms to planktonic levels of
antibiotic sensitivity, suggesting the ADI pathway is influential in biofilm-related
antibiotic treatment failure and provides a new strategic target for the treatment of biofilm
infections in GAS and potentially numerous other bacterial species.IMPORTANCE Biofilm-mediated
bacterial infections are a major threat to human health because of their recalcitrance to
antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form
antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to
acid stress plays in biofilm growth and
antibiotic tolerance. This not only provides some insight into
antibiotic treatment failure in S. pyogenes
infections but also, given the widespread nature of this pathway, provides a potentially broad target for antibiofilm
therapies. This discovery has the potential to impact the treatment of many different types of recalcitrant biofilm
infections.