Volatile profiling distinguishes Streptococcus pyogenes from other respiratory streptococcal species

Sore throat is one of the most common complaints encountered in the ambulatory clinical setting. Rapid, culture-independent diagnostic techniques that do not rely on pharyngeal swabs would be highly valuable as a point-of-care strategy to guide outpatient antibiotic treatment. Despite the promise of this approach, efforts to detect volatiles during oropharyngeal infection have yet been limited. In our research study, we sought to evaluate for specific bacterial volatile organic compounds (VOC) biomarkers in isolated cultures in vitro, in order to establish proof-of-concept prior to initial clinical studies of breath biomarkers. A particular challenge for diagnosis of pharyngitis due to Streptococcus pyogenes is the likelihood that many metabolites may be shared by S. pyogenes and other related oropharyngeal colonizing bacterial species. Therefore, we evaluated whether sufficient metabolic differences are present that distinguish the volatile metabolome of Group A streptococci from other streptococcal species that also colonize the respiratory mucosa, such as S. pneumoniae and S. intermedius. In this work, we identify candidate biomarkers that distinguish S. pyogenes from other species, and establish highly produced VOCs that indicate presence of S. pyogenes in vitro, supporting future breath-based diagnostic testing for streptococcal pharyngitis. IMPORTANCEAcute pharyngitis accounts for approximately 15 million ambulatory care visits in the USA. The most common and important bacterial cause of pharyngitis is Streptococcus pyogenesis, accounting for 15% to 30% of pediatric pharyngitis. Distinguishing between bacterial and viral pharyngitis is key to management in US practice. Culture of a specimen obtained by throat swab is the standard laboratory procedure for the microbiologic confirmation of pharyngitis, however this method is time consuming which delays appropriate treatment. If left untreated, S. pyogenes pharyngitis may lead to local and distant complications. In this study, we characterized the volatile metabolomes of S. pyogenes and other related oropharyngeal colonizing bacterial species. We identify candidate biomarkers that distinguish S. pyogenes from other species and provides evidence to support future breath-based diagnostic testing for streptococcal pharyngitis.