Inhibition of multiple staphylococcal growth states by a small molecule that disrupts membrane fluidity and voltage.

New molecular approaches to disrupting bacterial infections are needed. The bacterial cell membrane is an essential structure with diverse potential lipid and protein targets for antimicrobials. While rapid lysis of the bacterial cell membrane kills bacteria, lytic compounds are generally toxic to whole animals.

A small molecule that disrupts S. Typhimurium membrane voltage without cell lysis reduces bacterial colonization of mice.

As pathogenic bacteria become increasingly resistant to antibiotics, antimicrobials with mechanisms of action distinct from current clinical antibiotics are needed. Gram-negative bacteria pose a particular problem because they defend themselves against chemicals with a minimally permeable outer membrane and with efflux pumps. During infection, innate immune defense molecules increase bacterial vulnerability to chemicals by permeabilizing the outer membrane and occupying efflux pumps.

Staphylococcal Bacterial Persister Cells, Biofilms, and Intracellular Infection Are Disrupted by JD1, a Membrane-Damaging Small Molecule.

Rates of antibiotic and multidrug resistance are rapidly rising, leaving fewer options for successful treatment of bacterial infections. In addition to acquiring genetic resistance, many pathogens form persister cells, form biofilms, and/or cause intracellular infections that enable bacteria to withstand antibiotic treatment and serve as a source of recurring infections. JD1 is a small molecule previously shown to kill Gram-negative bacteria under conditions where the outer membrane and/or efflux pumps are disrupted.

Teaching Undergraduates to Communicate Science, Cultivate Mentoring Relationships, and Navigate Science Culture.

The historic underrepresentation of women, certain racial and ethnic minorities, and members of other marginalized groups in careers in science, technology, engineering, and mathematics (STEM) reflects a disproportionate exit of individuals from these academic and career paths due to both environmental and personal factors. To transition successfully from classroom-based learning to the research environment, students must acquire various forms of capital nested within a largely hidden curriculum that most scientists learn informally. We have developed a semester-long course for undergraduate researchers that makes explicit concepts and strategies that contribute to STEM persistence.

A small molecule that mitigates bacterial infection disrupts Gram-negative cell membranes and is inhibited by cholesterol and neutral lipids.

Infections caused by Gram-negative bacteria are difficult to fight because these pathogens exclude or expel many clinical antibiotics and host defense molecules. However, mammals have evolved a substantial immune arsenal that weakens pathogen defenses, suggesting the feasibility of developing therapies that work in concert with innate immunity to kill Gram-negative bacteria. Using chemical genetics, we recently identified a small molecule, JD1, that kills Salmonella enterica serovar Typhimurium (S.