Trimodal Response of Escherichia coli and Proteus mirabilis to Penicillins

Abstract

IT has been generally believed that penicillins act on Gram-negative bacilli by interfering with cell wall synthesis leading to the release of spheroplasts which then succumb to osmotic damage. Such damage is usually fatal although in conditions of suitably high osmolarity the spheroplast phenomenon is known to be reversible¹. Using turbidimetric methods supported by morphological studies in the scanning electron microscope, we have recently demonstrated that Escherichia coli and Proteus mirabilis show a variety of responses to penicillins which cannot be satisfactorily explained on the basis simply of the emergence and subsequent osmotic destruction of spheroplasts^2,3. With the high bacterial population densities used, large numbers of “persisters” (organisms which survive exposure to bactericidal concentrations of penicillin although their progeny remain fully sensitive⁴) could be recovered after prolonged exposure to penicillins, and it seemed that this survival resulted from yet another response to the agents. In this investigation we have extended our studies and have attempted to elucidate the persister phenomenon.