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Neo-Darwinian natural selection theory indicates that sudden, drastic changes in the environment place selective pressure on genetic variants in a population. As time progresses, this pressure sculpts individuals to better fit this new environment. Waddington’s classic experiment was repeated using white-eyed (the w1118strains) flies which produced the crossveinless (cve; disturbed wing crossveins) trait from the parent generation. The F1 generation was split into two selection lines: an Upward Selection Line, that produced more cve in successive generations, and a Downward Selection Line that responded with a consistent but non-linear decline in the percentage of crossveinless. This article will introduce and enlarge observations made on flies with cve; especially the manner in which the Waddington experiment impacts the population. It seems that Waddington evaluated crossveinless just by what it is good for, but not by the price of using it. That is to say, there is an inevitable cost that needs to be paid in order to acquire crossveinless-ness (cve and the associated phenotypes).
Iclaprim is a novel bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia caused by Gram-positve bacteria. Daptomycin, linezolid and vancomycin are commonly used antibiotic for these indications. With increase selective pressure to these generic antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid or vancomycin. Iclaprim had an MIC ≤1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 71.4%), linezolid (26 of 26 100%), or vancomycin (19 of 28 66.7%). In time-kill curves analyses, iclaprim demonstrated ≥3 log10 reduction in CFU/mL at 4-8 hours for tested strains and isolates nonsusceptible to linezolid or vancomycin. Together these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid or vancomycin.