Bacterial Stress Responses: How bacteria adapt to their environment.
Bacteria adapt to an ever-changing environment, and this requires specific mechanisms to sense their surroundings and deploy defensive responses. These bacterial stress responses are critical during interaction of both commensal and pathogenic bacteria with the human host. The innate immune system restricts the growth of invading bacteria by limiting access to essential nutrient metal ions (nutritional immunity) and by production of antimicrobial peptides and enzymes that attack the cell envelope. Using Bacillus subtilis as a model system, we characterize the bacterial stress responses elicited by metal ion limitation and excess, and by antibiotics that interfere with integrity of the cell envelope. This NIH-funded basic research program provides insights into those mechanisms that allow bacterial cells (both beneficial and harmful) to adapt to the host environment.
Interested in joining our team?
We are recruiting at all levels, seeking talented and motivated individuals. Please email Dr. Helmann with a CV and a cover letter indicating your career goals and what research areas excite you the most. Our mission is to help you push the boundaries of knowledge, gain new skills and perspectives, and advance your career goals.
Antibiotics that act on the cell envelope (including vancomycin and bacitracin) trigger global stress responses coordinated, in part, by alternative sigma subunits for RNA polymerase. Some of the genes induced by antibiotic stress play a direct role in antibiotic resistance, a growing problem among Gram positive pathogens.
Exposure of cells to reactive oxygen and nitrogen species (such as hydrogen peroxide, superoxide, and nitric oxide) induces the expression of multiple regulons coordinated by several different transcription factors. For example, we have described both PerR and OhrR as regulators that directly sense reactive oxygen species. Resistance to oxidative and nitrosative stress is important for many bacterial pathogens.
Metal ion homeostasis
To grow in the complex and varied environment of the soil, B. subtilis must be able to obtain all essential metal ions while at the same time excluding (or actively effluxing) toxic metal ions. We have described transcription factors that directly sense Fe(II), Mn(II), Zn(II), and Cu(I) and regulate the expression of the corresponding uptake and/or efflux systems.
Students in our laboratory can expect to gain experience in a wide range of techniques as applied to this model genetic system. Most research projects will include some or all of the following:
Whole-genome resequencing, TnSeq, ChIP-seq, computer-based approaches to defining regulons
Mariner mutagenesis, forward genetics, transformation, transduction
CRISPR-gene editing, site-directed and PCR-based mutagenesis
Protein purification, in vitro transcription, enzyme assays