Studies on Penicillinase: III. The Effect of Antipenicillinase on Penicillin-resistant Organisms.

Numerous reports (Carpenter et al., 1944; Spink et al., 1945; Tainter, 1945) have been recorded in the literature describing increased resistance of bacteria to various chemotherapeutic substances, including antibiotics. Increased resistance of organisms to penicillin has been observed (Spink et al., 1945; Tainter, 1945; Demerec, 1945). In the latter case, attempts have been made to control infections caused by resistant organisms either by increasing the dosage of penicillin or by substituting another antibiotic or drug (Spink et at., 1945; Wolnisky and Steenken, 1946). Methods for preventing the development of resistance or for increasing the susceptibility of resistant organisms may be developed if the cause for this phenomenon can be determined. One of several possible factors involved in such resistance is the production, by certain organisms, of penicillinase, an enzyme capable of destroying penicillin. A correlation between the production of penicillinase and resistance to penicillin has been recorded in some cases (Kirby, 1944). In other resistant species, however, no penicillinase could be detected (Bondi and Dietz, 1944). Spink and Ferris (1945) found penicillinase in cultures made resistant to penicillin in vivo but none in those made resistant in vitro. These studies indicate that the production of penicillinase is not the sole factor in resistance, but it may well play an important role in certain instances. The possibility of enzyme inhibition by specific antibody (Sevag, 1945) was made use of by Perlstein and Liebmann (1945a), who produced antipenicillinase-immune serum and demonstrated that it protected penicillin from destruction by penicillinase (Perlstein and Liebmann, 1945b). No such results were obtained using normal serum. They postulated the formation of a penicillin, plasma protein complex which protects penicillin in vitro from destruction by penicillinase. Actually, such a theory is not necessary since the simple combination of antigen (penicillinase) and antibody (antipenicillinase) should prevent destruction of penicillin. The question also arises why antipenicillinase serum proteins should have an affinity for penicillin different from that of normal serum. All antibodies studied to date are globulins, and penicillin combines with normal albumin but not normal globulin (Chow and McKee, 1945). Even the albuminpenicillin complex proved to be active.