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Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001. K. J. Christiansen, 2004.Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin . Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 µg/ml . Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin . For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S . aureus (ORSA) . Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 µg/ml for only 9% of them . For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries . No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 µg/ml . There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs . For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 µg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated . No mutations conferring high-level resistance were detected . Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region . In particular, it has good activity against S . aureus and S . pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance . Experimental Determination and System Level Analysis of Essential Genes in Escherichia coli MG1655. S. Y. Gerdes, 2003.Defining the gene products that play an essential role in an organism's functional repertoire is vital to understanding the system level organization of living cells . We used a genetic footprinting technique for a genome-wide assessment of genes required for robust aerobic growth of Escherichia coli in rich media . We identified 620 genes as essential and 3,126 genes as dispensable for growth under these conditions . Functional context analysis of these data allows individual functional assignments to be refined . Evolutionary context analysis demonstrates a significant tendency of essential E . coli genes to be preserved throughout the bacterial kingdom . Projection of these data over metabolic subsystems reveals topologic modules with essential and evolutionarily preserved enzymes with reduced capacity for error tolerance . High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction. Sunny Park, 2003.Escherichia coli is generally resistant to H2O2, with >75% of cells surviving a 3-min challenge with 2.5 mM H2O2 . However, when cells were cultured with poor sulfur sources and then exposed to cystine, they transiently exhibited a greatly increased susceptibility to H2O2, with <1% surviving the challenge . Cell death was due to an unusually rapid rate of DNA damage, as indicated by their filamentation, a high rate of mutation among the survivors, and DNA lesions by a direct assay . Cell-permeable iron chelators eliminated sensitivity, indicating that intracellular free iron mediated the conversion of H2O2 into a hydroxyl radical, the direct effector of DNA damage . The cystine treatment caused a temporary loss of cysteine homeostasis, with intracellular pools increasing about eightfold . In vitro analysis demonstrated that cysteine reduces ferric iron with exceptional speed . This action permits free iron to redox cycle rapidly in the presence of H2O2, thereby augmenting the rate at which hydroxyl radicals are formed . During routine growth, cells maintain small cysteine pools, and cysteine is not a major contributor to DNA damage . Thus, the homeostatic control of cysteine levels is important in conferring resistance to oxidants . More generally, this study provides a new example of a situation in which the vulnerability of cells to oxidative DNA damage is strongly affected by their physiological state .
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