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SRI’s Microbiology Program performs research and development on infectious diseases with serious unmet medical needs. Rising drug resistance to existing therapeutics and the emergence of pathogens with high intrinsic drug resistance has created an important need for new therapeutic strategies and diagnostics.
Mycobacterium tuberculosis (Mtb), the causative agent of TB, is responsible for approximately two million deaths each year and remains a major public health hazard throughout the world. Existing treatments for both drug-sensitive TB and multi-drug resistant TB (MDR-TB) require prolonged treatment durations (six months for drug-sensitive TB, 18 to 24 months for MDR-TB) and are difficult to administer. The goal of our program is to identify new treatments for MDR-TB that can be used in combination with existing drugs in order to shorten the duration of treatment and have fewer side effects.
Drug-Resistant Gram-Negative Bacteria
The development of antibacterial drugs against gram-negative bacteria pathogens is particularly challenging due to the presence of an outer membrane that prevents many classes of drugs from entering the cell. Our specific focus is on the pathogen Acinetobacter baumannii, an organism responsible for increasing numbers of hospital infections, is inherently resistant to many classes of antibiotics through several different mechanisms. Our research is on new ways to sensitize A. baumannii to existing antibiotics and the development of new drug combinations for treating this highly drug-resistant bacteria.
The goal of this project is to develop new lead compounds targeting the B subunit of the bacterial DNA gyrase enzyme. The fluoroquinoline class of antibiotics target the A subunit of DNA gyrase and are one of the most successful classes of broad-spectrum antibiotics on the market. Increased resistance to fluoroquinolines has lead to the investigation of gyrase B inhibitors as an alternative antibacterial strategy for targeting the same DNA gyrase complex. We have developed a novel binding assay for identifying compounds that can bind to the ATP-binding site of gyrase B and are using this to screen to identify novel classes of compounds that inhibit this essential bacterial target.
Technologies are developed with potential for industrial scale-up to protect the environment and human health. For example, SRI has used anaerobic sulfate reducing bacteria to reductively remove sulfur from petroleum products; used fungi to produce ethanol from cellulosic material; and is developing an adsorption enhanced photo-catalytic water purification bioreactor.
SRI uses state-of-the-art Biosafety Level 2 (BSL2) and BSL3 laboratories to conduct in vitro antimicrobial screening assays with potential novel anti-infectives against aerobic, facultative anaerobic, and strict anaerobic bacterial pathogens, yeasts, fungi, and protozoans. Screening is also performed with select agents in the biodefense field.