NEWS OF THE WEEK BIOCHEMISTRY
NEW ROUTE FOUND TO TB DRUG RESISTANCE TB-causing bacteria are shielded from antibiotics by DNA-mimicking protein HE THREE-DIMENSIONAL terium to another, notes John S. structure ofa protein maxm- Blanchard of Albert Einstein ColfactwedbyMycobocteriumtu-lege of Medicine. One such proberculosis suggests a new strategy tective protein, dubbed Qnr, "has SPITTING IMAGE MfpA [top) mimics DNA's (bottom) by which the tuberculosis-causing been appearing in lots of clinical size, shape, and charge distribution. organism may be able to outma- strains of fluoroquinolone-resistneuver fluoroquinolone antibi- ant bacteria," Blanchard tells tweaked to design DNA mimics otics {Science 2005,308,1430). C&EN. that specifically target other Fluoroquinolones, particularM. tuberculosis bacteria make a DNA-binding proteins. Such dely moxifloxacin and gatifloxacin, similar protective protein, named signer DNA mimics could find are becoming increasingly im- MfpA, according to Blanchard. use as therapeutics for tubercuportant in the fight against TB, He, Subray S. Hedge, Matthew losis and other diseases that can especially against strains that are W. Vetting, and coworkers now be treated by blocking the repliresistant to multiple antibiotics. report that MfpA bears a strik- cation machinery, he proposes. — These drugs kill bacteria by in- ing resemblance to DNA. The AMANDA YARNELL terfering with DNA gyrase, a finding "was completely unexDNA-binding enzyme that pre- pected," Blanchard says. vents the bacterium's genomic The team's 2.0-A-resolution C O N G R E S S DNA from becoming tangled picture of MfpA shows that the during replication. Fluoroquin- dimeric protein folds into a rightolones bind to the DNA-bound handed helix, with extensive gyrase and prevent the enzyme hydrogen-bonding interactions from doing its work. between the peptide backbone he Senate Judiciary Committee approved an asbestos trust fund bill (S. 852) on May 26. The bill would take asBut resistance to these impor- atoms of adjacent square-shaped bestos injury claims out of litigation and pay them from a tant antibiotics is on the rise, coils. The protein's overall size, notes David C. Hooper, an in- shape, and charge distribution $ U 0 billion trust fund. fectious diseases expert at Mass- closely mimic that of normal BAll Republicans on the committee and three Democrats supachusetts General Hospital. So formDNA. ported the legislation, approving it on a 13-to-5 vote. far, nearly all fluoroquinolone-re- The similarity to DNAhas led Although 50 amendments were added to the bill to satisfy sistant M. tuberculosis strains out- Blanchard's team to suggest that concerns of Judiciary Committee members, passage by the full smartfluoroquinolonesby just MfpAand its relatives interact di- Senate will not be easy. Three Republicans on the panel who one mechanism: They can make rectly with DNA gyrase. They approved the bill say that more changes will have to be made a modified DNAgyrase that isn't demonstrate that MfpAfitsnice- before they vote for it on the Senate floor. susceptible to the antibiotics. ly into the enzyme's DNA-bindSenators who are uncertain about the bill are worried about Recently,fluoroquinolonere- ing site. Blanchard suggests that, costs. They say it is not known how many claimants would sistance also has been observed in the presence of MfpA, DNA qualify for compensation, which defendant companies and inin other disease-causing bacteria, gyrase does not form the DNA- surers would contribute to the fund, and how much each would including Shigella and Escherichiabound gyrase complex that is the contribute. coli. Instead of making a modified fluoroquinolone target, renderBackers of the bill include the National Association of DNAgyrase, however, these bac- ing the drug useless. Manufacturers, the Asbestos Workers Union, and the auto teria produce a small protein that This novel mechanism may be workers union. protects DNAgyrase from inhi- responsible for the rapid spread But the Association of Trial Lawyers of America (ATLA), the bition byfluoroquinolone.Such of fluoroquinolone resistance Environmental Working Group, and several victims' groups opstrains are worrisome because the that's making multi-drug-resist- pose the legislation. Victims' groups say the medical criteria in genetic instructions for making ant bacterial infections so diffi- the bill would unnecessarily exclude many asbestos victims. the protective protein are con- cult to treat, Blanchard says. The "This bill is about as far from perfect as you can get. It's undertained in a DNAplasmid that can new structure also suggests that funded, unfair, unworkable, and likely unconstitutional," says be passed rapidly from one bac- the sequence of MfpA could be ATLA President Todd A. Smith.-BETTE HILEMAN
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Asbestos Bill Moves Out From Committee
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C & E N / J U N E 6. 2005
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