Research Interests

Role of low-molecular-weight thiols in bacteria

In the cell, low molecular weight thiols are responsible for the reducing environment needed for biochemical reactions to occur, act as cofactors for various metabolic reactions, and protect the cell against oxidants and electrophiles. While glutathione is the major thiol in gram-negative bacteria and higher organisms, most gram-positive bacteria do not contain glutathione. In the high GC Actinomycetes, mycothiol substitutes for glutathione and we have recently demonstrated that bacillithiol is the major thiol in the low GC Firmicutes. A third thiol, ergothioneine, is found in almost all organisms but was previously thought to be synthesized only by fungi and Actinomycetes. Recently, the biosynthetic pathway of this thiol has been elucidated and the genes shown to be present in a wide variety of bacteria including cyanobacteria. These thiols differ in their chemical structure and thus it is possible that they serve complementary functions in the bacterial cell. One aspect of my research program concerns unique thiols of bacteria and the function of these thiols in the bacterial cell. We are especially interested in the role of thiols in coping with environmental stress, detoxification, and the contribution of these thiols to inherent drug resistance in bacteria. In addition, I am interested in the genes and enzymes involved in the biosynthesis and metabolism of these thiols and the potential of these genes and enzymes as novel drug targets.

Detoxification of dyes by Actinomycetes

A second aspect of my research concerns the capacity of bacteria, in particular mycobacteria, as bioremediators of toxic dyes. Dyes and dye products are major pollutants that are often mutagenic and toxic to a wide range of organisms. Recently, stringent legislation has made it imperative that economically feasible methods be developed to detoxify triphenylmethane, azo, and anthraquinone dyes. It is well known that mycobacteria are able to detoxify the triphenylmethane dye malachite green, since this dye is added to the Middlebrook media used for culturing Mycobacterium tuberculosis. We are using genetic tools such as transposon mutagenesis to understand the genetic basis of decolorization and degradation of malachite green in Mycobacterium smegmatis.