Prof. Shimon Schuldiner

UPCOMING EVENTS

Esmeralda submits a new paper

Esmeralda Z. Reyes-Fernández, a new postdoc in the lab joined us from Mexico after a Ph.D. at Max Planck Research School for Environmental, Cellular and Molecular Microbiology (IMPRS-Mic), Marburg, Germany

The findings are novel and exciting. While the paper is under consideration for publication you can have a look below and at Bioxriv. 

Biochemistry
Seminar
 Thursday at 12PM during the academic year
Will be back after Corona pandemics ends

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. 

The Hebrew University of Jerusalem

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