Cyclic-di-GMP phosphodiesterase STM3615 regulates Salmonella physiology
Abstract
Foodborne-related diseases pose a global health threat, with Salmonella being a leading cause worldwide. To develop better prevention strategies against Salmonella-related food poisoning, we need a deeper understanding of how Salmonella senses its environment to adjust its behavior and enhance its chances of survival. One way bacteria achieve this is through second messengers, molecular signals that help relay this type of information. A key second messenger of interest is cyclic-di-GMP that bacteria use to regulate genes that enhance survival and infectious potential by influencing processes such as biofilm formation, flagellar motility, and virulence. Previous studies identified the cyclic-di-GMP phosphodiesterase STM3615 as important for Salmonella survival inside macrophages and virulence in a mouse model. Here, we investigated STM3615’s role in Salmonella physiology. Using a dye-based agar assay, we found that deleting STM3615 reduced survival in the stationary phase. Microscopy revealed that the mutant also exhibited a shorter bacterial morphology. Given that both phenotypes relate to bacterial division, we tested its susceptibility to A22, an antimicrobial that disrupts bacterial replication machinery, and observed significantly reduced survival. STM3615 contains multiple domains, including transmembrane, periplasmic, HAMP, and phosphodiesterase (PDE) domains. Surprisingly, the periplasmic domain, rather than the PDE domain responsible for breaking down cyclic-di-GMP, emerged as the key regulator of bacterial morphology and division. A protein fold prediction algorithm suggested STM3615 interacts with a periplasmic protein partner to mediate this response. Using random transposon mutagenesis, we identified mutations in the Rcs pathway—linked to envelope stress and morphology regulation—that restored wild-type phenotypes. Future research will investigate STM3615’s interactions with a periplasmic binding partner to further define its role in cell division. Understanding this mechanism could provide new insights into bacterial growth regulation, with implications for therapeutic strategies and infection control.
Start Time
16-4-2025 10:00 AM
End Time
16-4-2025 11:00 AM
Room Number
303
Presentation Type
Oral Presentation
Presentation Subtype
Grad/Comp Orals
Presentation Category
Science, Technology and Engineering
Faculty Mentor
Erik Peterson
Cyclic-di-GMP phosphodiesterase STM3615 regulates Salmonella physiology
303
Foodborne-related diseases pose a global health threat, with Salmonella being a leading cause worldwide. To develop better prevention strategies against Salmonella-related food poisoning, we need a deeper understanding of how Salmonella senses its environment to adjust its behavior and enhance its chances of survival. One way bacteria achieve this is through second messengers, molecular signals that help relay this type of information. A key second messenger of interest is cyclic-di-GMP that bacteria use to regulate genes that enhance survival and infectious potential by influencing processes such as biofilm formation, flagellar motility, and virulence. Previous studies identified the cyclic-di-GMP phosphodiesterase STM3615 as important for Salmonella survival inside macrophages and virulence in a mouse model. Here, we investigated STM3615’s role in Salmonella physiology. Using a dye-based agar assay, we found that deleting STM3615 reduced survival in the stationary phase. Microscopy revealed that the mutant also exhibited a shorter bacterial morphology. Given that both phenotypes relate to bacterial division, we tested its susceptibility to A22, an antimicrobial that disrupts bacterial replication machinery, and observed significantly reduced survival. STM3615 contains multiple domains, including transmembrane, periplasmic, HAMP, and phosphodiesterase (PDE) domains. Surprisingly, the periplasmic domain, rather than the PDE domain responsible for breaking down cyclic-di-GMP, emerged as the key regulator of bacterial morphology and division. A protein fold prediction algorithm suggested STM3615 interacts with a periplasmic protein partner to mediate this response. Using random transposon mutagenesis, we identified mutations in the Rcs pathway—linked to envelope stress and morphology regulation—that restored wild-type phenotypes. Future research will investigate STM3615’s interactions with a periplasmic binding partner to further define its role in cell division. Understanding this mechanism could provide new insights into bacterial growth regulation, with implications for therapeutic strategies and infection control.