Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus

Bravo-Santano, N., Capilla-Lasheras, P. , Mateos, L. M., Calle, Y., Behrends, V. and Letek, M. (2019) Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus. Scientific Reports, 9, 15435. (doi: 10.1038/s41598-019-51894-3) (PMID:31659191) (PMCID:PMC6817851)

[img] Text
233470.pdf - Published Version
Available under License Creative Commons Attribution.



During patient colonization, Staphylococcus aureus is able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes during S. aureus infection and we identified several host genes important for this intracellular pathogen. In addition, we interrogated our screening results to find novel host-targeted therapeutics against intracellular S. aureus. We found that silencing the human gene TRAM2 resulted in a significant reduction of intracellular bacterial load while host cell viability was restored, showing its importance during intracellular infection. Furthermore, TRAM2 is an interactive partner of the endoplasmic reticulum SERCA pumps and treatment with the SERCA-inhibitor Thapsigargin halted intracellular MRSA survival. Our results suggest that Thapsigargin could be repurposed to tackle S. aureus host cell infection in combination with conventional antibiotics.

Item Type:Articles
Additional Information:This work was supported by a Roehampton Vice Chancellor’s Scholarship to NBS, a Royal Society Research Grant to M.L. (Ref. RG130658), a New Lecturer Research Grant of the Society for Applied Microbiology to V.B., and intramural funding from the University of Roehampton to M.L. and V.B. P.C.L. was funded by a BBSRC-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1).
Glasgow Author(s) Enlighten ID:Capilla Lasheras, Dr Pablo
Authors: Bravo-Santano, N., Capilla-Lasheras, P., Mateos, L. M., Calle, Y., Behrends, V., and Letek, M.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9: 15435
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record