Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes.

Herrlich, Peter; Schweiger, Manfred

doi:10.1073/pnas.73.10.3386

Cited by 55 publications

(21 citation statements)

References 32 publications

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“…This is in accordance with the data on the inhibition of the ,B-lactamase production by other antibacterial drugs that inhibit protein synthesis (1,7,13,14,18). On the other hand, we found the same percentage of experiments in which subMIC's of the drugs increased the penicillinase production.…”

Section: Discussionsupporting

confidence: 81%

Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus

Michel¹,

Stessman²,

Stessman³

1980

Antimicrob Agents Chemother

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The influence of subminimal inhibitory concentrations of erythromycin, clindamycin, and pristinamycin on the penicillinase production of Staphylococcus aureus was tested in 12 strains. Of the 36 experiments performed, 16 (44%) showed a lack of influence, 10 (28%) displayed an increase, and 10 revealed a decrease in penicillinase activity. The maximal effect produced was generally induced by concentrations ranging from ¼/ to 1/32 the minimal inhibitory concentration, irrespective of the susceptibility of the strain to the drug. In spite of the fact that the drugs are closely related, they sometimes produced opposite effects on the same strain.The problem of the effects of subminimal inhibitory concentrations (subMIC's) of antibacterial drugs has been investigated in the last few years and was recently discussed by Lorian (9) and Rolinson (15). Most of the available data concern the influence of various agents on bacterial growth (2,6,17) and the morphological changes induced by. the subMIC's of f,-lactam antibiotics (4,8,10,12). Only a few papers have dealt with the effects of the subMIC on bacterial enzymatic systems. Inducible enzymes were shown to be affected by the subMIC's of nitrofurans (7) and chloramphenicol (18). Gemmell has reported the influence of the subMIC's of antibiotics, especially .clindamycin, on the biosynthesis of some staphylococcal toxins and enzymes during experimental pyogenic infection (5). We have shown that the subMIC of chloramphenicol can inhibit ,8-lactamase production in gram-negative bacilli (13) and in Staphylococcus aureus (14) and that this inhibition sometimes leads to a synergistic bactericidal effect in vitro (13,14) and in vivo (16). More recently, Allen and Epp have shown that erythromycin can inhibit penicillinase induction in strains of S. aureus (1). To the best of our knowledge, a comparative study on the effect ofclosely related drugs on penicillinase production has not been reported in the literature. The purpose of the present paper was, therefore, to investigate the influence of subMIC's of erythromycin, clindamycin, and pristinamycin on the penicillinase production of strains of S. aureus. MATERIALS AND METHODSTwelve strains of penicillin G-resistant S. aureus were used. These were isolated in the diagnostic laboratory of the Department of Clinical Microbiology, Hadassah University Hospital, Mount Scopus, Jerusalem, from sputum, wound exudates, urine, and blood. Each was tested for ,B-lactamase production by the iodometric method, as described by Workman and Farrar (21). The minimal inhibitory concentrations (MICs) of erythromycin, clindamycin, and pristinamycin for these strains were determined by using a microdilution technique. Serial twofold dilutions of the antibiotic were made in tryptic soy broth (TSB; Difco Laboratories) in sterile Microtiter U-plates (Cook Engineering Co.). A suitable dilution of a 4-h culture of the bacteria in TSB at 37°C was prepared in TSB and added to the wells of the microtiter plates to give a final inoculum of 10' colony-forming ...

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Section: Discussionsupporting

confidence: 81%

Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus

Michel¹,

Stessman²,

Stessman³

1980

Antimicrob Agents Chemother

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“…Nonspecific aggregation among Escherichia coli F-cells results in 5-25% of the cells being aggregated. However, F' or Hfr cultures show additional conjugation-specific aggregation such that 15-45% of these cells are self-aggregated. § In efficient F' X F-(or Hfr X F-) mating mixtures, 70% of all cells are to be found in mating aggregates resistant to sodium dodecyl sulfate (NaDodSO4).…”

mentioning

confidence: 99%

“…Plasmid DNA was isolated by ethidium bromide/CsCl density gradient centrifugation and used, after ethanol precipitation, as the template in an in vitro protein-synthesizing system (12,15). Proteins synthesized in this system were labeled with 14C-labeled amino acids and separated on gradient NaDodSO4/ polyacrylamide gels as above.…”

mentioning

confidence: 99%

Cell--cell interactions in conjugating Escherichia coli: role of traT protein in surface exclusion.

Achtman¹,

Kennedy²,

Skurray³

1977

Proc. Natl. Acad. Sci. U.S.A.

180

145

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Escherichia coli cells carrying the F sex factor are poor recipients in conjugation. This phenomenon is called surface exclusion. Two F cistrons, traS and traT, are independently responsible for part of the whole mechanism. The traS gene product reduces DNA transfer within stable mating aggregates. The tra T gene product, pTraT, results in a greatly reduced ability to form stable mating aggregates, and thus also leads to reduced DNA transfer within the cell population. pTraT is a 25,000-dalton protein incorporated into the cell envelope outer membrane. It is found in 29,000-84,000 copies per cell, depending on the plasmid expressing it. There is a parallel variation in recipient ability. Models for surface exclusion are discussed.Many bacterial sex factors not only code for the ability to act as donors and to transfer DNA, but they also reduce the ability of their hosts to act as recipients in conjugation with other donors. We refer to this phenomenon as surface exclusion. It is specific in that only conjugation with donors carrying closely related sex factors is inhibited (1). Surface exclusion is a result of active expression of the sex factor DNA because it can be alleviated, at least partially, either by growing cells into stationary phase (2) or by isolating mutants of the sex factor (3, 4). It has been argued (5) that surface exclusion is a result only of the inhibition of DNA transfer, without any effect on the formation of cell contacts. Our data here and elsewhere (6) do not support this view.We have analyzed bacterial conjugation and surface exclusion with the physical techniques of electronic particle analysis (Coulter counter) and electron microscopy (6-8). The results demonstrated that conjugation occurs in mating aggregates containing between 2 and 50 cells each, and that the aggregates are of variable composition in regard to their donor/recipient ratio (7). Furthermore, the formation of these mating aggregates involves several stages (8). F pili are necessary for the initial interactions, and then unstable wall-to-wall contacts occur. The wall-to-wall contacts are stabilized, and DNA transfer can then take place.

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“…It is, however, still not known with certainty which target in bacterial metabolism is mainly responsible for its antimicrobial effect. Nitrofurans have been reported to interfere with carbohydrate metabolism (Hamilton-Miller & Brumfitt, 1976), with the synthesis of RNA and polysome assembly (Tu & McCalla, 1976)1, and with the translation of the mRNA of enzymes subjected to catabolite repression (Herrlich & Schweiger, 1976). The mutagenic and carcinogenic properties of nitrofurans are well established (Anon., 1976;McCalla, 1979).…”

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confidence: 99%

Nitrofurantoin Prompts the Stringent Response in Bacillus subtilis

López

Fortnagel

1981

Microbiology

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Nitrofurantoin causes the stringent response in Bacillus subtilis. After exposure of a stringent strain to this drug, the intracellular concentrations of guanosine 3'-diphosphate 5'-diphosphate (ppGpp), guanosine 3'-diphosphate 5'-triphosphate (pppGpp) and ATP increased, while that of GTP decreased. In a relaxed strain no accumulation of ppGpp or pppGpp was observed, but both GTP and ATP declined after the addition of nitrofurantoin. Protein synthesis was equally sensitive to nitrofurantoin in both the stringent and relaxed strains, but the drug inhibited RNA accumulation only in the stringent strain, not in the relaxed strain. Nitrofurantoin also caused the accumulation of ppGpp in Escherichia coli and Serratia marcescens.

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Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes.

Cited by 55 publications

References 32 publications

Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus

Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus

Cell--cell interactions in conjugating Escherichia coli: role of traT protein in surface exclusion.

Nitrofurantoin Prompts the Stringent Response in Bacillus subtilis

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