Fatty Acid Modulation of Autoinducer (AI-2) Influenced Growth and Macrophage Invasion by Salmonella Typhimurium

Autoinducer-2 (AI-2) is a small molecule that is involved in bacterial cell-to-cell signaling whose precursor formation is mediated by luxS. A luxS mutant of Salmonella Typhimurium PJ002 (Delta luxS) was grown in glucose-containing M-9 minimal medium supplemented with varying concentrations (1x, 10x, and 100x) of long-chain fatty acids (linoleic acid, oleic acid, palmitic acid, and stearic acid) to study the influence of fatty acids on growth rate and macrophage invasion. Additionally, in vitro synthesized AI-2 was added to this medium to identify the influence of AI-2 on S. Typhimurium PJ002 (Delta luxS) growth rate and macrophage invasion. The growth rate constant (k) for each experimental treatment was determined based on OD600 values recorded during 12 h of incubation. There was a significant (p = 0.01) increase in the growth rate of S. Typhimurium PJ002 (Delta luxS) in the presence of AI-2 when compared to the phosphate-buffered saline (PBS) control. However, fatty acids either singly or in a mixture were unable to influence AI-2's effect on growth rate. The presence of AI-2 significantly (p = 0.02) decreased the invasiveness of S. Typhimurium PJ002 (Delta luxS) towards the murine macrophage cell line, RAW 264.7. However, the fatty acid mixture was able to reverse this reduction and restore invasiveness to background levels. These results suggest that, while AI-2 may enhance the growth rate and reduce macrophage invasion by the luxS mutant S. Typhimurium PJ002 (Delta luxS), fatty acids may influence the virulence in S. Typhimurium (PJ002) by modulating AI-2 activity.