507 Eugenia
Madison 5, Wis

May 3, 1956

Dear Joe:

Just a passing thought gleaned on reading an article by Sixkiny Cooper
on mechanism of penicillin action in current Bact Rev. He quotea a finding
that penicillinanide is considerably more resistant to penicillinase than
penicillin itself, Why not sereen for other resistant modifications of peni-
llin: E.G.: add a good slug of penicillin to your fermentation broths (I know
many actinos are susceptible to it); after the fermentation, add penioillinase
and assay product on penicillinsensitive and resistant indicators, The point
is that penicillinase is the main basis of resistance in natural populations,
and the other advantages of penicillin might well be retained in a penicillinase-
resistant conjugate of penicillin; the actinos would simply be screened for
their ability to modify penicillin, Most lab--resistant mutants have another
mechanism of resistance besides penicillinase, and I would expect cross- resistance
here with the hypothetical conjugates.

Yra

Joshua Lederberg