Daptomycin resistant Staphylococcus aureus clinical isolates are poorly sensed by dendritic cells
- Author(s)
- Patton, T; Jiang, JH; Lundie, RJ; Bafit, M; Gao, W; Peleg, AY; O'Keeffe, M;
- Journal Title
- Immunology and Cell Biology
- Publication Type
- Journal Article in press
- Abstract
- Methicillin resistant Staphylococcus aureus (MRSA) presents an increasing threat to public health, with antimicrobial resistance on the rise and infections endemic in the hospital setting. Despite a global research effort to understand and combat antimicrobial resistance, less work has focused on understanding the nuances in the immunopathogenesis of clinical strains. In particular, there is a surprising gap of knowledge in the literature pertaining to how clinical strains are recognised by dendritic cells (DC). Here, we show that the activation of DC is compromised in response to MRSA strains resistant to the last line antibiotic daptomycin. We found a significant reduction in the secretion of proinflammatory cytokines including TNF-alpha, IL-6, RANTES and MIP-1beta, as well as decreased expression of CD80 by dendritic cells responding to daptomycin-resistant MRSA. We further demonstrate that this phenotype is coincident with the acquisition of specific point mutations in the cardiolipin synthase gene cls2, and, partly, in the bifunctional lysylphosphatidylglycerol flippase/synthetase mprF, which are genes that are often mutated in clinical daptomycin-resistant strains. Therefore, throughout infection and antibiotic therapy, MRSA has the capacity to not only develop further antibiotic resistance, but also develop resistance to immunological recognition by DC, due to single amino acid point mutations occurring under the selective pressures of both host immunity and antibiotic therapy. Understanding the diversity of clinical MRSA isolates and the nuances in their immune recognition will have important implications for future therapeutics and the treatment of these infections.
- Publisher
- WIley
- Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- 31559654
- Publisher's Version
- https://doi.org/10.1111/imcb.12295
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-10-23 02:22:53
Last Modified: 2019-10-23 02:44:27