Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Streptococcus pyogenes is a human pathogen responsible for various diseases. To cause diseases, S. pyogenes must adapt in adverse environments, such as acidic environment in the wound. The acid stimuli may trigger S. pyogenes invading from a mucosal to subepithelial tissue. However, how acid stimulates S. pyogenes to manipulate secretome for causing invasive infection is unclear. To investigate secretome change under acidic environment, a comparative secretomics by label-free LC-MS/MS was used to analyze the secretome from acidic and neutral conditions. The growth curves of S. pyogenes in acidic and neutral conditions are similar, which reveals that S. pyogenes can grow well during environmental acidification. The protein patterns on SDS-PAGE show prominent dissimilarity between the secretomes in acidic and neutral conditions. It demonstrates protein secretion is influenced by acid stress. The dynamic label-free LC-MS/MS profiling identified 172 proteins which are influenced by environmental acidification. Among these, 45 (28%) the identified proteins are predicted secreted proteins. Interestingly, the predicted secreted proteins occupy about 90% of protein abundance of secretome in acidic condition at stationary phase. In contrast, only 30% shows in neutral condition. It exhibits that acid is crucial for secreted protein expression. There are 21 pathogenesis-related secreted proteins effecting immune evasion, hemolysis, adhesion, tissue damage, and nutrient acquisition. The 24 non-pathogenesis-related secreted proteins could be potential virulence factors involved in invasive infection. Two known acid-induced proteins, SpeB and Pilin, are also observed. Several novel candidates, such as streptococcal histidine triad protein, CAMP, and biofilm regulatory protein A, are of special interests. This investigation provided key information for elucidating the broad influences and underlying mechanisms related to acidified environment for group A streptococcal infection.

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