杏吧原创

FROM the lush forests of Costa Rica and the farming heartlands of Wisconsin
come two possible weapons in the fight against the antibiotic-resistant
superbugs prowling the wards of hospitals the world over.

One hopeful bulletin comes from the Guanacaste Conservation Area in northern
Costa Rica, where researchers have isolated fungal extracts which kill the two
most feared superbugs, methacillin-resistant Staphyloccocus aureus
(MRSA) and vancomycin-resistant enterococci. The other source of hope
comes from the University of Wisconsin in Madison, where a promising antibiotic
in frog skin has been engineered to make it more potent and less prone to
breaking down in patients鈥� bodies.

Jon Clardy and his colleagues in the department of chemistry at Cornell
University in Ithaca, New York, named the new fungal substances guanacastapenes
after the place they were found in Costa Rica. 鈥淭hey鈥檝e been collected under a
programme set up by the US government,鈥� explains Clardy. If the substances do
turn out to be lucrative pharmaceuticals, Costa Rica will receive a cut of the
profits.

Clardy and his team isolated the new substances from fungi thriving in
branches of the Costa Rican tree, Daphnopsis americana. The filamentous
fungi live in cells of the plant鈥檚 fluid circulation system, and produce the
substances to ward off rival microorganisms. 鈥淚t鈥檚 a tough world out there,鈥�
says Clardy. In lab tests, guanacastapene was lethal to MRSA and VRE, he says.
However, it also ruptured red blood cells in animals in later tests by
collaborators at Wyeth-Ayerst, the pharmaceuticals giant in Pearl River, New
York. This might mean that the extract is too dangerous to use as an
antibiotic.

But Clardy鈥檚 team has since isolated a further dozen variants from the same
fungus which, they hope, will be just as lethal to superbugs without the side
effects. 鈥淲e鈥檙e purifying them until we have enough to test,鈥� he says.

Meanwhile, at the University of Wisconsin in Madison, Sam Gellman and
colleagues have made artificial versions of magainins, an emerging class of
natural antibiotics. Derived from the skin of Xenopus lupus, the African
clawed frog, magainins could become the first of a new class of antibiotics
derived from animals rather than microorganisms
(New 杏吧原创, 22 June 1996, p 20).

Gellman created hardier, artificial variants of natural magainins by
replacing the usual amino acid building blocks of the peptide molecules with
artificial 鈥渂eta鈥� amino acids which don鈥檛 exist in nature. He and his colleagues
in the chemistry department hope that the revised versions will make more robust
antibiotics because they cannot be broken down in the body by digestive enzymes,
unlike their natural counterparts. Also, the structure is more stable.
鈥淐onventional peptides are floppy pieces of spaghetti,鈥� says Gellman. 鈥淥urs has
a much more regular structure,鈥� he says.

Michael Zasloff of Magainin Pharmaceuticals in Pennsylvania, says that the
beta amino acids could provide new tools for recrafting magainins. And John
Coia, a microbiologist at the Western General Hospital in Edinburgh, welcomes
the developments, but warns: 鈥淭here鈥檚 a long way between finding a substance
with antibiotic action and making it into a drug.鈥�