No abstract

Plasmid-mediated chloramphenicol resistance in Staphylococcus aureus has been shown to involve acetylation of chloramphenicol by an enzyme induced by growth in the presence of the antibiotic and certain analogues. Analysis of the kinetics of induction has been complicated by (i) the intrinsic inhibitory effects of chloramphenicol on induced enzyme synthesis and (ii) the rapid disappearance of inducer after synthesis of the acetylating enzyme. The compound related to D-threo chloramphenicol which lacks a C3 hydroxyl substituent (3-deoxychloramphenicol) is a potent inducer of chloramphenicol acetyltransferase but is ineffective as an antibiotic and is not a substrate for the enzyme. The availability of such a "gratuitous" inducer has simplified an analysis of the kinetics of induction of chloramphenicol acetyltransferase. The enzyme from induced bacteria has been purified to homogeneity and has been compared with the analogous enzyme present in E. coli which harbors a resistance transfer factor with the chloramphenicol resistance determinant.

Nalidixic acid (NAL) is bactericidal for E. coli B. Synthesis of deoxyribonucleic acid (DNA), ribonucleic acid and protein was necessary to initiate the lethal effect, but only protein synthesis was necessary to sustain it. NAL inhibited DNA synthesis specifically, but this inhibition occurred even under conditions that were not lethal to the bacteria. In contrast to other inhibitors of DNA synthesis, NAL did not cause the solubilization of cellular DNA even when bacteria were exposed to it for 2 hr. A bacterial mutant deficient in DNA polymerase was much more sensitive to the lethal action of NAL than its parent strain. Moreover, inhibition of protein synthesis did not protect this mutant from NAL-induced killing. NAL inhibited neither DNA polymerase, nor thymidine or thymidylate kinases. The data are interpretated as suggesting that NAL altered the structure of DNA or a protein attached to nascent DNA and that this lesion can be partially repaired by DNA polymerase.

The Enterobacter species E. aerogenes, E. cloacae, and E. hafnia were examined for resistance to penicillin and cephalosporin derivatives. All were resistant to benzyl penicillin, ampicillin, 6 [D(-)a-amino-p-hydroxyphenylacetamido] penicillanic acid, cephaloridine, cephalothin, and cephalexin. A significant number were sensitive to carbenicillin and 6 [D(-)a-carboxy-3-thienylacetamido] penicillanic acid. No differences among the three species were noted. The ,B-lactamase activity was cell-bound, and was not released by osmotic shock, toluene treatment, or diphenylamine treatment. It was rarely released into the growth medium. The f-lactamase activity was primarily directed against cephalosporin derivatives. Synthesis of ,3-lactamase was chromosomally mediated. Resistance to ampicillin seemed to be partly related to entry of the molecule into the bacteria since exposure to ethylenediaminetetraacetate lowered the minimal inhibitory concentration.

Serratia marcescens strains were divided into three groups on the basis of antimicrobial sensitivity and pigment production. Group I, nonpigmented, was resistant to most antibiotics. Group II, nonpigmented, was susceptible to many antimicrobial agents, as was group III which was pigmented. Representative organisms of each group were examined for all lipid content. There were no significant differences in total lipid, phospholipid, or fatty acid esters among the three groups. Differences in susceptibility to antibiotics in Serratia do not seem to be explained on the basis of wall lipid content.