Christopher D. Radka, Ph.D., assistant professor in the Department of Microbiology, Immunology, and Molecular Genetics, is a corresponding author on a new study that sheds light on how Staphylococcus aureus can evade one of the body’s earliest defenses against infection.
The study, recently published in Proceedings of the National Academy of Sciences, describes an unexpected connection between how bacteria process fats and how the immune system responds to infection.
S. aureus is a common cause of skin and soft tissue infections and can be particularly difficult to treat because the bacteria can survive inside cells, where they can evade both immune defenses and antibiotics.
Researchers found that S. aureus uses an enzyme called oleate hydratase (OhyA), to convert fatty acids from its host into a different type of lipid. The bacteria then secrete these lipids, which interfere with a signaling pathway called TLR3–TRIF–IRF7.
That pathway has traditionally been associated with the body’s response to viruses, particularly when cells detect double-stranded RNA. The new findings show that activating the pathway could play an important role in defending cells against intracellular S. aureus.
Researchers also found that the OhyA-produced lipid can protect neighboring bacteria, suggesting that S. aureus does more than shield itself from immune detection. By secreting the lipid, the bacteria can create an environment that helps other bacteria persist as well.
“This discovery reveals a defined lipid-mediated immune-evasion mechanism in S. aureus, showing how the pathogen repurposes host fatty acids into signals that suppress innate immune sensing,” said Radka. “Remarkably, rather than targeting a host receptor, cytokine or bacterial PAMP, OhyA converts a common host lipid into a small, hydroxylated metabolite that ultimately dampens a nucleic acid-sensing pathway.”
Radka shared that because OhyA is bacterial while its substrate pool is host-derived, it represents an attractive therapeutic target.
“Inhibiting OhyA, or selectively blocking the resulting suppressive lipid signal, could restore innate immune function without imposing the selective pressures associated with conventional bactericidal antibiotics.”
The findings challenge the traditional view that the immune system uses separate pathways to recognize viruses and bacteria. Instead, they reveal an unexpected point of overlap between antiviral immune machinery and antibacterial defense.
By understanding how S. aureus suppresses this early immune response, Radka and his colleagues may be able to find new ways to strengthen the body's defenses against intracellular bacterial infections, including infections that are difficult to eliminate with antibiotics alone.
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R00AI166116 and the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM159612. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.