Research Interests
Role of low-molecular-weight thiols in bacteria
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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. |