The widespread emergence of antibiotic-resistant bacteria and a lack of new pharmaceutical development have catalyzed a need for new and innovative approaches for antibiotic drug discovery. One bottleneck in antibiotic discovery is the lack of a rapid and comprehensive method to identify compound mode of action (MOA). Since a hallmark of antibiotic action is as an inhibitor of essential cellular targets and processes, we identify a set of 308 essential genes in the clinically important pathogen Staphylococcus aureus. A total of 446 strains differentially expressing these genes were constructed in a comprehensive platform of sensitized and resistant strains. A subset of strains allows either target underexpression or target overexpression by heterologous promoter replacements with a suite of tetracycline-regulatable promoters. A further subset of 236 antisense RNA-expressing clones allows knockdown expression of cognate targets. Knockdown expression confers selective antibiotic hypersensitivity, while target overexpression confers resistance. The antisense strains were configured into a TargetArray in which pools of sensitized strains were challenged in fitness tests. A rapid detection method measures strain responses toward antibiotics. The TargetArray antibiotic fitness test results show mechanistically informative biological fingerprints that allow MOA elucidation.

ender disparity in academic promotion has been investigated among physicians in the United States. 1,2 After age, experience, specialty and research productivity are accounted for, women are less likely than men to be full professors. 2 Markers suggestive of inequity, defined as a lack of fairness, in academia also exist among Canadian professors, with women representing only 27.6% of full professors 3 and receiving on average $10 263 less than men in annual salary. 4 In addition, women account for just 12% of faculty of medicine deans. 5 With respect to specialty-specific disparity, the barriers faced by women are more pronounced in surgical careers. 6 Despite recent increases, women still represent only 27% of Canadian surgeons 7 and an even lower proportion of academic surgeons. 6 Studies show consistent challenges faced by women, such as the perception of fewer career advancement opportunities, 8 suboptimal maternity leave and child care, 7,9 gender-based discrimination, 10 an "old boys' club" culture of practice 11 and a lack of female mentors. 12,13 Despite similarities in gender disparity within Canadian and US academia, perhaps the long-standing female majority among medical graduates and increased proportion of female surgical trainees in Canada have allowed for the correction of the inequities of the previous era (i.e., the pipeline effect).