Prof. Shimon Schuldiner
After 45 years
I was lucky enough to lead a research group with talented and dedicated people, and today I close my lab with satisfaction and gratitude after almost half a century.
I close the lab, but I move to my office and continue reading, evaluating manuscripts and grants. I am busy advising those interested and, here and there, collaborating with others. I am still due to finish one or two papers from work done by my students. I hope to continue contributing, albeit in a different form, to understand how transporters function and how they are involved in cell physiology and disease.
Thursday at 12PM during the academic year
OUR LATEST RESEARCH
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The decreasing effectiveness of antibiotics in treating common infections has quickened in recent years, and resistance has spread worldwide. There is an urgent need to understand the mechanisms underlying acquisition and maintenance of resistance, and here we identify a novel element in the chain of events leading to a full-fledged clinically relevant state. The Escherichia coli multiple antibiotic resistance (mar) regulon is induced by a variety of signals and modulates the activity of dozens of target genes involved in resistance to antibiotics. We report here a thus far unidentified result of this activation: acidification of the cytoplasmic pH. Manipulation of the cytoplasmic pH with weak acids and basis, independently of the mar response, shows that the acidification significantly increases resistance.
Antibiotic resistance is a growing global public health concern and was recently defined by the Center for Disease Control as among the most urgent problem facing physicians today. We show here that multidrug transporters are essential for acquisition of high-level, clinically significant antibiotic resistance. To achieve high-level resistance, multiple mutations accumulate sequentially, each providing a small but distinct increase in fitness. Transporters decrease the cytoplasm concentration to values that allow fixation of single mutations. We identified transporters that are essential for the acquisition of resistance to quinolones, we different types of transporters work in a concerted mode and we show that the function of the major transporter AcrAB-TolC can be partially backed up by other TolC-dependent ones.