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Updated: May 22, 2026
Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
cGAS/STING sensing in dendritic cells discriminates between daptomycin sensitive and resistant Staphylococcus aureus
Timothy Patton1,2, Nazneen Jahan1, Jhih-Hang Jiang3,4
1Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Abstract:
Antimicrobial-resistant infections present significant threats to public health, predicted to cause 10 million fatalities annually by 2050. Of these infections, one of the most frequent is methicillin-resistant Staphylococcus aureus (MRSA). During therapeutic exposure to last-line antibiotics, including daptomycin, MRSA often acquires genetic mutations conferring resistance. Resistance is typically mediated through structural alterations to the bacterial cell wall and membrane, which we have previously shown, concomitantly impede the activation of responding dendritic cells (DCs). Here, we demonstrate how MRSA acquisition of daptomycin resistance impedes innate immune sensing by DC. We show that the acquisition of daptomycin resistance reduced phagocytosis by DC, and that it impaired the recognition of resistant isolates via the cytoplasmic cGAS/STING pathway, affecting the production of cyclic dinucleotides produced by both the host and the bacterium. Our research uncovers a mechanism by which antibiotic resistance mutations can simultaneously hinder the innate immune system's ability to recognize bacteria.
Insights
Antibiotic-resistant MRSA infections hinder the immune system. Daptomycin-resistant MRSA impairs dendritic cell sensing, reducing phagocytosis and cGAS/STING pathway activation, thus evading immune detection.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Antimicrobial resistance (AMR) poses a significant global health threat, with MRSA being a common pathogen.
- MRSA frequently develops resistance to last-line antibiotics like daptomycin through genetic mutations.
- These resistance mechanisms can alter bacterial cell structures, impacting host immune responses.
Purpose of the Study:
- To investigate how daptomycin resistance in MRSA affects innate immune sensing by dendritic cells (DCs).
- To elucidate the specific mechanisms by which resistant MRSA evades DC recognition and activation.
Main Methods:
- Comparative analysis of daptomycin-susceptible and daptomycin-resistant MRSA strains.
- Assessment of phagocytosis efficiency by DCs.
- Evaluation of the cytoplasmic cGAS/STING pathway activation in DCs upon encountering resistant MRSA.
Main Results:
- Daptomycin-resistant MRSA exhibited reduced phagocytosis by DCs compared to susceptible strains.
- Resistant MRSA impaired the recognition of bacterial isolates via the cGAS/STING pathway.
- This impairment affected the production of cyclic dinucleotides by both host and bacterium.
Conclusions:
- MRSA's acquisition of daptomycin resistance impedes innate immune sensing by DCs.
- Resistance mutations concurrently hinder the innate immune system's ability to recognize and respond to bacteria.
- This dual effect highlights a critical mechanism of immune evasion by antibiotic-resistant pathogens.
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