Open AccessA horizontally gene transferred copper resistance locus enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in host cells
Author(s) -
Daniella Lucy Spencer,
Inderpreet Kaur,
Joanne Purves,
Peter W. Andrew,
Paul J. Planet,
Joan A. Geoghegan,
Kevin J. Waldron,
Julie A. Morrissey
Publication year - 2020
Publication title -
access microbiology
Language(s) - English
Resource type - Journals
ISSN - 2516-8290
DOI - 10.1099/acmi.ac2020.po0765
Subject(s) - efflux , staphylococcus aureus , microbiology and biotechnology , biology , gene , phagosome , virulence , locus (genetics) , methicillin resistant staphylococcus aureus , innate immune system , immune system , bacteria , genetics , phagocytosis
The spread of community acquired, methicillin resistant Staphylococcus aureus (CA-MRSA) is an increasing problem seen outside the healthcare setting. One such strain, CA-MRSA USA300, is epidemic in the United States. USA300 shows a heightened resistance to the innate immune system, in particular to macrophage engulfment. Two horizontally acquired genes, encoding an efflux pump (CopX) and lipoprotein (CopL), were discovered in 2 different lineages of USA300, representing CA-MRSA epidemics in North and South America. Removal of either of these genes resulted in elevated copper concentrations in the cytoplasm of S. aureus , implying a function in copper hyper-resistance. While copper is an essential part of metabolic machinery, it is toxic at high concentrations and is utilised by macrophages to kill bacteria in the phagosome. Supporting this, USA300 with functional copXL genes showed increased survival in macrophages compared to their copXL negative counterparts. Although the role of CopX as an efflux pump explains the rise in intracellular copper concentration upon its mutation, the role of the CopL lipoprotein is still unknown. Therefore, to better understand the function of CopL and how it might influence S. aureus host interaction, transcriptomic analysis is underway to identify downstream targets. This has the potential to uncover an exciting mechanism linking metal resistance to host virulence.