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Jeff Boyd
Assistant Professor
Rutgers University
Dept. of Biochemistry and Microbiology
School of Env & Biol Sciences
Lipman Hall. Room 329
76 Lipman Drive
New Brunswick. N. J. 08901-0231
(848) 932-5604
FAX - 8965
jmboyd@aesop.rutgers.edu |
Bacterial pathogenesis, iron-sulfur clusters, oxidative
stress, environmental sensing
Detection and response of organisms to oxidative
stress, biological iron-sulfur cluster assembly and repair
We are currently working on two interrelated projects in our lab.
The first project examines the physiological response of a
pathogenic bacterium to oxidative stress. The second project uses
a model organism to dissect how organisms metabolize small oxidant
sensitive inorganic cofactors.
1) Staphylococcus aureus is a human commensal bacterium that is
naturally carried by 20-50% of the population. This bacterium can
cause infections that range from relatively harmless furuncles and
carbuncles to life threatening endocarditus and necrotizing
pneumonia. Staphylococcus aureus infections have historically been
associated with open-wounds, hospital visits, and immuno-compromised
persons, but recently, infections are being seen in relatively
healthy individuals that have not been associated with hospital
settings (community acquired infections). Many of these infections
are caused by strains of S. aureus that are resistant to nearly
all commonly used antibiotics, including methicillin, greatly
complicating the treatment of infections caused by this aggressive
pathogen.
One research focus of our laboratory is to determine how
community-acquired methicillin-resistant Staphylococcus aureus
(CA-MRSA) detects and responds to host defense systems.
Neutrophil granulocytes are white blood cells that provide humans
with a “first line” of defense against CA-MRSA infections.
Neutrophils engulf and kill bacteria, in part, by bombarding them
with poisonous oxidants such as bleach, superoxide, and hydrogen
peroxide. Remarkably, strains of CA-MRSA can survive this attach
and successfully invade host tissues. Our lab uses a variety of
biochemical and genetic techniques to understand what is unique
about the physiology of CA-MRSA that allows it withstand high
degrees of oxidative stress. We also study how CA-MRSA detects and
responds to the presence of neutrophils and oxidative stress.
2) The second focus of our work examines the metabolism of simple
inorganic cofactors called iron-sulfur (Fe-S) clusters. Proteins
with [Fe-S] clusters have an ever-expanding repertoire of
biological functions. These metalloproteins are involved in some
of the most fundamental life-sustaining processes on Earth such as
biological nitrogen fixation, photosynthesis, and cellular
respiration. To this end, the evolution of all life can be
considered dependent on the successful and controlled synthesis
and maintenance of [Fe-S] clusters. Free iron and free sulfur are
toxic to cells and Iron-sulfur clusters are easily damaged by
oxidants. Therefore, complex cellular machinery has evolved to
tightly control the synthesis and repair of [Fe-S] clusters.
Despite the recognized and central role of [Fe-S] clusters in
biology, our understanding of how these inorganic cofactors are
metabolized is limited by our lack of basic knowledge in which
gene products control the synthesis, trafficking, and repair of
these clusters and how these gene products are integrated into
cellular metabolic networks.
The work on our second project aims to address remaining
questions in [Fe-S] cluster metabolism and take advantage of
integrative studies to uncover the biochemical function of genes
of unknown function involved in [Fe-S] metabolism.
Because all cells face similar challenges in integrating their
metabolism and many metabolic paradigms are conserved, these
studies are conducted using the model bacterium Salmonella
enterica for simplicity and technical feasibility.
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