218 NATURE OF ANTIBIOTIC ACTION 



INHIBITION OF BACTERIOSTATIC AND 

 BACTERICIDAL ACTION 



The formation of specific chemical compounds capable of inhibiting, 

 inactivating, or even destroying bacteriostatic and bactericidal sub- 

 stances of microbial origin has been established for a number of anti- 

 biotic agents. 



Yeasts were found to contain a substance which inhibits the action of 

 sulfanilamide against 5. hemolytkus as well as other streptococci and 

 pneumococci. This substance has been identified (771) with the 

 ^-amino-benzoic acid referred to above. No relationship could be estab- 

 lished, however, between the growth-promoting properties and anti- 

 sulfanilamide activity of the yeast extract (544). 



Br. abortus and certain other bacteria also contain (354, 355) a fac- 

 tor, designated as "p," which specifically inhibits the bacteriostatic ac- 

 tion of sulfanilamide. This factor stimulates markedly the growth of 

 many bacteria, and is not specific. The sensitivity of sulfanilamide de- 

 pends on the rate of release of the factor from the bacterial cell and not 

 on the total amount produced. This factor was believed to stimulate 

 some enzyme reaction concerned with bacterial reproduction, whereas 

 sulfanilamide inhibits this reaction. Similar factors have been isolated 

 from yeast (870) and from hemolytic streptococci (538). It is also 

 known that certain substances, like methionine, inhibit the growth- 

 stimulating effect of biotin (259). 



To what extent antibiotic substances can be inhibited in their action 

 against bacteria still remains to be determined. Certain few facts have 

 so far been established. 



Bacteria not inhibited by penicillin were found (4, lOOO) to be ca- 

 pable of producing a substance which destroys the growth-inhibiting 

 property of the antibiotic agent. The penicillin-destroying substance is 

 believed to be an enzyme, since it is destroyed by heating at 90° C. for 

 5 minutes. It was designated as "penicillinase." The optimum fYi of its 

 action was found to be 8 to 9. The presence or absence of this enzyme 

 in bacteria is independent of the sensitivity of the organism to peni- 

 cillin. Bacterial extracts, pus fluids, peptone, and ^-amino-benzoic acid, 

 which interfere with the action of sulfonamides, do not affect penicillin. 



Cephalin and extracts of gram-negative bacteria, of milk, and of 



