Overuse of antibiotics has led to an increased number of infections that are antibiotic resistant. Therefore, the development of new antimicrobials is a necessity. Synthetic compounds are explored and used for such activity. In parallel, plant based phytochemicals are also popular in antimicrobial applications. While synthetic compounds can be accurately characterized, plant extracts can not be easily characterized despite their diverse therapeutic applications. However, lack of such characterization has not impeded their popularity. This project aims at approaching the antimicrobial properties from multiple facets: the study of promising synthetic organic compounds and plant extracts individually and then together to understand the synergistic effect. Specifically, a variety of novel indolinone derivatives will be synthesized and characterized for the biological assay. Concurrently, phytochemicals from readily available herbs, spices and other sources will be isolated. Their potential to inhibit bacterial growth will be determined using a standard disk diffusion assay on several different species of bacteria including E. coli and Staphylococcus aureus. The potential of the compounds to target specific bacterial systems will also be investigated. Some pathogenic bacteria including E. coli, Salmonella, Shigella, Chlamydia and Yersinia species utilize a type III secretion system (T3SS), which are needle-like structures on their surface used to inject host cells with toxins in order to evade our immune system and cause infection. The ability of the compounds to inhibit bacterial T3SSs will be determined using a novel assay for screening that will be designed to be less complex and less expensive. Results of these experiments can lead to the development of novel antimicrobial drugs. Student researchers will reinforce their skills (acquired from courses) as well as acquire new ones. The students will also participate in presentations (at scientific conferences) and manuscript preparation (for peer reviewed scientific journals) in order to disseminate their findings.