Congratulations to Dr Rebecca Corrigan whose lab group have had a new paper published in the Journal of Infectious Diseases. Dr Corrigan collaborated with colleagues at the University of Sheffield and using a zebrafish embryo infection model, coupled with human macrophage studies, show that nucleotide stress signalling systems are important for MRSA virulence by promoting bacterial adaptation to the phagolysosome. The paper is titled, ‘Determining the importance of the stringent response for methicillin-resistant Staphylococcus aureus virulence in vivo’.
Explaining the research and its importance, Dr Corrigan states, ‘‘The ‘superbug’, methicillin resistant Staphylococcus aureus (MRSA) is a major threat to global health. While this human pathogen can reside in the nose of approximately 20% of the population, if it gains entry to the bloodstream it can cause bacteraemia with a mortality rate of up to 43%. Together with colleagues at the University of Sheffield, we have pioneered zebrafish embryos as a powerful model for studying MRSA infection and host-pathogen interaction in vivo. Using this model, we reveal that bacterial stress signalling nucleotides are crucial for MRSA infection. Here these nucleotides enable bacteria to adapt to conditions within human innate immune cells, helping bacteria to survive, grow and cause infection. Our work provides insights into how this superbug causes infection, which can hopefully be used to develop new treatment strategies in the future."
Abstract
The stringent response is a stress signalling pathway with links to bacterial virulence. This pathway is controlled by the nucleotide alarmone (p)ppGpp, produced in Staphylococcus aureus by three synthetase enzymes. Here, we used a panel of synthetase mutants to examine the importance of this signalling network for S. aureus survival and virulence in vivo. Using a zebrafish larval infection model, we observed that infection with a (p)ppGpp null strain attenuated virulence. Zebrafish myeloid cell depletion restored the virulence during systemic infection, indicating that (p)ppGpp is important for phagocyte-mediated immune evasion. Primary macrophages infection studies, followed by in vitro tolerance assays and RNA-seq, revealed that (p)ppGpp is required to survive stressors found within the intracellular macrophage environment, with roles for each class of synthetase, and the linked transcription factor CodY, implicated. Taken together, these results define the importance of the stringent response and each class of synthetase for S. aureus infection.
The research is published here.
Dr Corrigan is also part of teams that have recently published papers in Langmuir (https://pubmed.ncbi.nlm.nih.gov/40747846/) with a study that focuses on the development of antibacterial nanoparticles, and in PNAS (https://pubmed.ncbi.nlm.nih.gov/40587784/) with work understanding how the cell surface of bacteria is constructed.