Quinolones are widely used, broad-spectrum antimicrobial agents. In screens for genes that, when overexpressed, allow Escherichia coli to grow on otherwise lethal concentrations of the fluoroquinolone norfloxacin, the ydhE gene was identified. We have shown that ydhE encodes a multidrug efflux pump with a narrower substrate range than that of its closest homologue, encoded by norM, and named the gene norE. The relative contributions to drug resistance of NorE compared with the two other known E. coli quinolone pumps, AcrAB and MdfA, have been defined. Overexpression of each of the three pumps separately resulted in roughly similar levels of quinolone resistance, whereas simultaneous overexpression of norE or mdfA in combination with acrAB gave synergic increases in quinolone resistance. The level of quinolone resistance mediated by efflux pumps seems to be constrained to an approximately 10-fold maximum, even with increased production of the pumps. We measured the drug resistance of an isogenic set of strains containing the various permutations of single, double and triple drug efflux pump mutants. The DeltanorE and DeltamdfA mutants were somewhat more susceptible to fluoroquinolones than the parent strain, and acrAB mutants were four- to six-fold more susceptible. Mutants lacking two or all three efflux pumps were not significantly more susceptible to fluoroquinolones than those lacking only one of the three pumps.
unveiled a new 7.5 million dollar program, NSF Graduate Teaching Fellows in K-12 Education (GK-12), to partner graduate students in the sciences with high school science teachers "... injecting new energy into ... K-12 positively influencing higher education-all while satiating a desperate hunger for mutual responsibility between all levels of science and mathematics education" (NSF PR 99-12; www.nsf.gov). In 2001, the program was expanded due to the positive responses from both higher education institutions and K-12 schools (NSF PR 01-27; vwww.nsf. ov). The program's design was to allow graduate fellows to serve as content advisors for teachers in science and mathematics; while providing improved communication, teaching, and community outreach skills for the graduate fellows. The GK-12 program ultimately will foster a strong, long lasting partnership between K-12 schools and higher-education institutions (http://www. ns. gov/home/crssprgm/gk 12/).
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