Triclosan's Unintended Role: Priming Staphylococcus aureus for Virulence
- Ray Sullivan
- 6 minutes ago
- 3 min read
The persistent battle against Staphylococcus aureus (S. aureus), a leading cause of infectious disease-related illness and death worldwide, is continually complicated by its remarkable adaptability and escalating antimicrobial resistance. Research led by Jeff Boyd's Lab in the Rutgers Department of Biochemistry & Microbiology, together with colleagues from Nutritional Sciences at Rutgers and New York University Grossman School of Medicine, has uncovered an unintended consequence of the common antimicrobial triclosan: it appears to activate key virulence pathways in S. aureus, potentially exacerbating its pathogenic potential.
At the heart of S. aureus's ability to coordinate its virulence arsenal is the SaeRS two-component regulatory system. This system acts as a master switch, controlling the expression of numerous virulence factors essential for pathogenesis. It comprises a membrane-spanning histidine kinase (SaeS) and a DNA-binding response regulator (SaeR). When host or physiological signals stimulate SaeS, it phosphorylates SaeR, increasing the transcriptional activity of genes encoding secreted virulence factors, including exotoxins, immune evasion factors, and proteases.
The activity of SaeRS is inversely linked to fatty acid levels; previous research demonstrated that the accumulation of fatty acids negatively impacts SaeS activity, thereby decreasing SaeR phosphorylation and subsequent virulence factor expression. Conversely, S. aureus responds to a depletion of fatty acids by stimulating SaeRS activity.
Triclosan, a synthetic antimicrobial found in countless personal hygiene products (e.g., soaps, toothpaste) and household materials, is widely recognized for its potent antibacterial properties. Its primary cellular target is enoyl-acetyl carrier protein reductase (FabI), a crucial enzyme in the bacterial type II fatty acid synthesis system. By inhibiting FabI, triclosan disrupts the elongation and synthesis of fatty acids within the bacterial cell.
Boyd et al. hypothesized that this inhibition of fatty acid synthesis by triclosan would alter the intracellular titers of fatty acids, consequently modulating SaeRS activity. Their findings strongly support this hypothesis:
Treatment of S. aureus with environmentally relevant concentrations of triclosan (e.g., 200 ng mL−1, comparable to levels found in human urine) significantly increased SaeRS transcriptional activity. This effect was robust even at lower triclosan concentrations (5 ng mL−1) used to avoid growth inhibition.
This SaeRS activation led to increased transcription and expression of genes coding for known virulence factors, such as hemolysins, proteins interacting with fibrinogen, and immune response modulators. Supernatants from triclosan-treated S. aureus also showed increased cytotoxicity towards human neutrophils and increased accumulation of leukocidin LukF, a SaeRS-controlled virulence factor.
The observed increase in virulence factor expression depended entirely on a functional SaeRS system; a ΔsaePQRS mutant strain showed no significant changes in saeP1 promoter activity upon triclosan treatment.
Fatty Acid Mechanism Confirmed:
Exogenous addition of oleic acid, which is known to inactivate SaeRS, chemically reversed the triclosan-dependent activation.
Genetic crippling of the FakAB fatty acid kinase system (which generates phosphorylated fatty acids for phospholipid incorporation) also reversed the triclosan-induced activation.
A S. aureus strain harboring a triclosan-resistant fabIF204Y allele did not exhibit SaeRS stimulation upon triclosan exposure, directly linking triclosan's effect to its inhibition of FabI.
Triclosan treatment decreased the overall concentration of cell-associated free fatty acids in S. aureus. However, unbiased lipidomics revealed a significant increase in specific fatty acids like arachidic acid (C20:0). Exogenous arachidic acid alone was sufficient to stimulate SaeRS activity in the wild-type strain. This suggests a model where triclosan's inhibition of FabI leads to a complex alteration in the fatty acid pool, with a specific accumulation of certain fatty acids that act as SaeRS activators.
These findings carry significant implications for public health. Triclosan is a persistent environmental pollutant, recalcitrant to natural degradation, leading to its widespread accumulation in aquatic ecosystems, sediment, and even the human body. Studies have detected triclosan in the urine of a large percentage of human participants, with concentrations ranging widely, often overlapping with the growth-permissive concentrations shown to activate S. aureus virulence in this study.
While it remains to be definitively determined if environmental or host-derived triclosan levels directly alter S. aureus pathogenesis in vivo, this research strongly suggests that our extensive use of triclosan could be inadvertently contributing to the virulence of S. aureus. For microbiologists, this study provides a critical new perspective on the complex interactions between antimicrobial agents, bacterial physiology, and virulence regulation. It highlights the urgent need for further research into widespread antimicrobial use's broader ecological and health impacts. It calls for reevaluating triclosan's role as a pervasive environmental contaminant.
Boyd JM, Price EE, Roman Rodriguez F, Burchat N, Norambuena J, DuMont AL, Torres VJ, Sampath H. Treatment of Staphylococcus aureus with environmentally relevant concentrations of triclosan activates SaeRS-dependent virulence factor expression. Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0172824. doi: 10.1128/aac.01728-24. Epub 2025 Jun 18. PMID: 40531055; PMCID: PMC12327003.