title: Early initiation of deoxyribonucleic acid replication and shortening of generation time associated with inhibition of lateral wall formation by mecillinam.
abstract: The effects of mecillinam on the growth of rods of the pH-conditional morphology mutant MirM7 was studied. It has been found that mecillinam causes, coincident with transition to coccal shape, a balanced rise in the rate of viable count increase and the rate of macromolecular synthesis which lasts either until the cells enter a stationary growth phase or indefinitely, in the case of continuously diluted cultures. When the antibiotic is removed from cells which have already become coccoid, cells continue to grow at a faster rate until they resume the rod shape. No change in the per-cell rate of protein synthesis has been seen in untreated or mecillinam-treated cells before or after the change in growth rate. Studies with synchronously growing cells have shown that the antibiotic causes a shortening in the I period (initiation of deoxyribonucleic acid replication). Evaluation of the residual divisions in nalidixic acid-treated, exponential-phase cells has shown that mecillinam also shortens the D period (cell division). It is proposed that, in strain MirM7, inhibition of lateral wall elongation by the antibiotic allows the initiation of a new septum, though inhibition is still in progress. The initiation of a new septum is, in turn, responsible for both the early inibition of deoxyribonucleic acid replication and accelerated division. In the parental strain, MirA12, as well as in other sensitive gram-negative rods which divide, become cocci, and stop dividing after addition of the antibiotic, inhibition of lateral wall formation activates a feedback mechanism which prevents insertion of new septa (Satta et al., J. Bacteriol. 142:43-51, 1980). Consequently, no early initiation of deoxyribonucleic acid replication is observed, and the last division allowed by the antibiotic occurs in due time. This negative control is missing in MirM7.
mesh_terms: D000560:Amdinocillin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis*; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D009268:Nalidixic Acid / Q000494:pharmacology; D010397:Penicillanic Acid / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009268:Nalidixic Acid; D010397:Penicillanic Acid; D000560:Amdinocillin