Novel peptide based antimicrobials are of great interest to my group. Whether ribosomally or non-ribosomally synthesized, these compound often contain complex structures and systems leading to their production. The discovery of unique structures and ascertaining their role in antimicrobial function are a fascinating area of research. Additionally, gaining an understanding of the function of the enzymes leading to their production is equally as interesting, because these enzymes may have utility in enzymatically synthesizing and engineering unique compounds. My strength in this area of research lies in my cross disciplinary background, which encompasses bacterial cultivation, bacterial genetics, fermentation and process biochemistry, structural determination using biophysical applications such as NMR and Mass Spectrometry, and experience in chemical modification and synthesis of natural products.

          The study of antimicrobials may lead to life saving therapies and help ensure a sustainable food supply. This in itself is enough to motivate my research efforts. However, there is more to antimicrobial research. This work also leads to a better understanding of microbial physiology and I am mesmerized by the complexity of the processes that microorganisms undergo to maintain a sustainable niche.

Lantibiotics

          Lantibiotics are an interesting class of antibiotics. Lantibiotics are a structurally novel class of antibiotics (Class I bacteriocins) which can be divided into 5 subclasses based on differences in their chemistry and biosynthesis: Type A(I), Type A(II), Type B, Two-Component and those of unknown structures. Lantibiotics possess sulfur-containing lanthionine rings and a large variety of unusual amino acids. This class of antibiotics is potent against a broad spectrum of Gram positive bacteria and has been known for decades but has not been extensively tested for their potential usefulness in treating infectious diseases. The main reason is that very little is known about the pharmaceutical potential of many of these antibiotics. This is primarily contributed to the difficulty of producing them in sufficient quantity and purity for preclinical and clinical tests. I have spent over a decade studying lantibiotics, particularly mutacin 1140 which belongs to the Type A "nisin" group of lantibiotics. My lab is currently working on approaches to make mutacin 1140 in sufficient amounts and purity to be cost effective. Furthermore, we are studying structural regions of the antibiotic to determine their importance during synthesis and in their bioactivity.

Antifungal peptides

This area of research is relatively new to me and begins with a fruitful collaboration with colleagues at Mississippi State University. One colleague isolated a bacterium, Burkholderia contaminans MS14, from soil that suppressed brown patch disease of lawn grass and initial characterization of the genomic loci responsible for its production suggests that the compound is non-ribosomally synthesized. Since initiating the collaborations, we have produced and purified the bioactive compound, characterized its covalent structure, tested the compounds activity against medically and agriculturally relevant pathogens, and initiated studies to determine the compound's mechanism of action. The compound has been named Occidiofungin, meaning fungal killer. There are still several interesting components left to be discovered in this project to keep me and many others entertained for awhile. In addition to Burkholderia contaminans MS14 strain, my colleague has other isolates demonstrating potent antifungal properties that we are currently studying.
 

CURRENT AND PAST FUNDING