Isolation of antibiotics from a species of Cephalosporium. Cephalosporins P1, P2, P3, P4 and P5

Abstract

A species of Cephalosporium produces a group of antibiotics that have been called collectively cephalosporin P, and an antibiotic with entirely different properties which has been named cephalosporin N. Cephalosporin P consists of acidic substances that are soluble in organic solvents, and are active mainly against Gram-pos. organisms. Cephalosporin N cannot be extracted from aqueous soln. by common organic solvents and is active against both Gram-pos. and Gram-neg. organisms. Crude cephalosporin P can contain at least 5 antibiotics, which have been named cephalosporin P1, P2, P3, P4 and P5. Cephalo-sporin P1 was the major active substance in extracts of the culture fluids that were used in the present work. By counter-current distribution between solvents and chromatography on Florisil, cephalosporins P1, P2 and P4 were isolated in crystalline form. Cephalosporin P1 is almost twice as active as helvolic acid against Staphylococcus aureus. but the 2 anti-biotics are similar in certain chemical and biological properties. Staphylococci that acquire resistance to cephalosporin P1 by growing in its presence become, at the same time, resistant to helvolic acid and vice versa. Cephalosporin P1 is inactivated by a prepn. of penicillinase containing a substance provisionally named P-cephalosporinase. The same prepn. of penicillinase also causes the inactivation of cephalosporins P2, P3, P4. P5, and helovlic acid.