176 BACTERIOLOGICAL CHEMISTRY 



/"// vilro, pr()l)al)ly duo to slow hydrolysis. Li doses of 

 about 2 nig. they will protect mice against many 

 thousand lethal doses of hsemolytic streptococci. 



As with other drugs, bacteria develop resistance to 

 penicillin when subjected to concentrations which are 

 inadequate for bacteriostasis. Organisms which have 

 acquired resistance to penicillin are still susceptible to 

 sulphonamides and vice versa. The mode of action of 

 penicillin is miknown but it does not interfere with 

 respiration ; susceptible organisms subjected to less 

 than the bacteriostatic dose continue to grow but lose 

 their power of subdivision so that giant forms are 

 produced. 



Penicillin is destroyed by enzymes (penicillinase) 

 secreted by several species of bacteria including E. coli, 

 Micrococcus lysodeikticus, Proteus and some Gram-positive 

 bacilli such as B. subtilis. 



Penicillin B. — This substance is identical with notatin. 



Proactinomycin. — A species of Proactinomyces, when 

 grown on a glucose agar medium, forms an alkaloid 

 like base, soluble in organic solvents and in water at 

 pH 4, which has bacteriostatic properties similar to, 

 but weaker than, those of penicillin. It is more stable, 

 undergoing only small loss of activity on boiling at 

 pK 2 or 7 for ten minutes ; it is inactivated by boiling 

 at pH 10. Proactinomycin is toxic to mice in doses of 

 2 to 5 milligrams. 



Puberulic Acid. — Several species of Penicillimn, P. 

 puberulum, P. aurantio-virens, P. joJiannioli and 

 Cyclopium viridicatum yield puberulic acid, CgHeOg, 



