The Role of Quorum Sensing and Stringent Response in Vibrio cholerae Antibiotic Resistance
Dr. David Raskin Ph.D
Medicine and Health Sciences
Vibrio cholerae is a Gram-negative bacterium that is the cause of the diarrheal disease cholera. Many strains have developed antibiotic resistance which allows these mutated strains to elude traditional treatment. Among the mechanisms that are proposed to contribute to antibiotic resistance are the quorum sensing genes and the stringent response. The stringent response is a bacterial defense mechanism in response to environmental stress in which gene expression is modified to divert resources from growth and division instead to long-term survival. Quorum sensing is a means of determining how many bacteria are present nearby and regulating genes according to that information, using the transcription factor HapR to activate or repress gene transcription. In our experiments, we explored how two closely related patient-derived cholera strains (C6706 and N16461), with combinations of deletions of the stringent response genes, responded to a large spectrum of antibiotics. On initial exploration, we discovered that stringent response played a role in resistance to antibiotics, but the C6706 strains seemed to demonstrate less antibiotic resistance than the N16461 strains. One of the major differences between these two strains is the presence of the quorum sensing transcription factor hapR in the C6706 strains, while N16961 contains a natural non-sense mutation in hapR and lacks quorum sensing regulation. To explore if the differences in antibiotic resistance profiles of C6706 and N16961 strains was due to quorum sensing, we created a deletion of hapR in C6706. We exposed C6706ΔhapR to the same initial antibiotics and found that there was little difference in antibiotic resistance between C6706ΔhapR and C6706. This indicated that the difference in resistance to antibiotics seen in C6706 and N16961 was not due to quorum sensing. Future experiments will test whether the stringent response regulatory system acts differently in N16961 and C6706, and if that plays a role in the different antibiotic resistance profiles of the strains.
Copyright 2019 all authors
Skelton, Alexis OMS-2 and Raskin, David Ph.D, "The Role of Quorum Sensing and Stringent Response in Vibrio cholerae Antibiotic Resistance" (2019). MU-COM Research Day. 146.