Projects per year
Abstract
It is increasingly apparent that bacteriophages, viruses that infect bacteria and more commonly referred to as simply phages, have tropisms outside their bacterial hosts. Using live tissue culture cell imaging, we demonstrate that cell type, phage size, and morphology play a major role in phage internalization. Uptake was validated under physiological conditions using a microfluidic device. Phages adhered to mammalian tissues, with adherent phages being subsequently internalized by macropinocytosis, with functional phages accumulating intracellularly. We incorporated these results into a pharmacokinetic model demonstrating the potential impact of phage accumulation by cell layers, which represents a potential sink for circulating phages in the body. During phage therapy, high doses of phages are directly administered to a patient in order to treat a bacterial infection, thereby facilitating broad interactions between phages and mammalian cells. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.
Original language | English |
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Article number | 102287 |
Number of pages | 32 |
Journal | iScience |
Volume | 24 |
Issue number | 4 |
DOIs | |
Publication status | Published - 23 Apr 2021 |
Keywords
- Immunology
- Microbiology
- Virology
Projects
- 4 Finished
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Development of a novel bacteriophage treatment regime to combat and re-sensitise multiply antibiotic resistant Acinetobacter baumannii infections
Barr, J. (Primary Chief Investigator (PCI))
1/02/19 → 31/01/21
Project: Research
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Bacteriophage therapy increases antibiotic sensitivities in multiply antibiotic resistant Acinetobacter baumannii
Barr, J. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/19 → 31/12/21
Project: Research
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ARC Training Centre for Personalised Therapeutics Technologies
Stewart, A. G. (Primary Chief Investigator (PCI)), Pfleger, K. (Chief Investigator (CI)), Voelcker, N. (Chief Investigator (CI)), Pébay, A. (Chief Investigator (CI)), Dottori, M. (Chief Investigator (CI)), Lee, P. (Chief Investigator (CI)), Elnathan, R. (Chief Investigator (CI)), O'Connor, A. J. (Chief Investigator (CI)), Rodger, J. (Chief Investigator (CI)), Palaniswami, M. S. (Chief Investigator (CI)), Doyle, B. (Chief Investigator (CI)), Kennedy, B. (Chief Investigator (CI)), Kameneva, T. (Chief Investigator (CI)), Heng, J. (Chief Investigator (CI)), Sercombe, T. (Chief Investigator (CI)), Pouton, C. (Chief Investigator (CI)), Zheng, M. (Chief Investigator (CI)), Mangum, J. E. (Chief Investigator (CI)), Volery, T. (Chief Investigator (CI)), Lim, C. T. (Partner Investigator (PI)), Herz, J. (Partner Investigator (PI)), Baker, M. L. (Partner Investigator (PI)), Lipscombe, R. (Partner Investigator (PI)), Anderson, P. (Partner Investigator (PI)), Keenan, M. (Partner Investigator (PI)), Barker, A. (Partner Investigator (PI)), Shand, T. (Partner Investigator (PI)), Smith, B. (Partner Investigator (PI)), Wadsworth, S. (Partner Investigator (PI)), Tan, A. (Partner Investigator (PI)), Rush, R. (Partner Investigator (PI)), Gooley, A. A. (Partner Investigator (PI)), Rose, S. E. (Partner Investigator (PI)), Nicholson, J. (Partner Investigator (PI)) & Munsie, M. (Chief Investigator (CI))
University of Melbourne, SMR Automotive Australia Pty Ltd, CSIRO - Future Manufacturing Flagship (Victoria), Trajan Scientific and Medical Pty Ltd, Monash University – Internal Faculty Contribution
11/05/18 → 11/05/24
Project: Research
Equipment
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Melbourne Centre for Nanofabrication (MCN)
Langelier, S. (Manager)
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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Monash Micro Imaging (MMI)
Firth, S. (Manager), Fulcher, A. (Operator), Chernyavskiy, O. (Operator), Rzeszutek, M. (Other), Potter, D. (Manager), Hilsenstein, V. (Operator), Nunez-Iglesias, J. (Other), Cody, S. (Manager), Carmichael, I. (Operator), Kouskousis, B. (Other), Creed, S. (Manager) & Ballerin, G. (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility