Lipiarmycin-resistant Ribonucleic Acid Polymerase Mutants of Bacillus Subtilis

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 1977 Oct 1

PMID 410787

Citations 18

Authors

A L Sonenshein

H B Alexander

D M Rothstein

S H FISHER

Affiliations

Soon will be listed here.

Abstract

Lipiarmycin inhibited the activity of deoxyribonucleic acid-dependent ribonucleic acid (RNA) polymerase in vitro. We showed that inhibition was due to interference by lipiarmycin with the activity of sigma-containing molecules of RNA polymerase. Transcription by core enzyme was relatively resistant to the drug, but addition of sigma led to highly drug-sensitive RNA synthesis. We isolated lipiarmycin-resistant mutants of Bacillus subtilis and characterized them genetically and biochemically. Drug-resistant mutants contained an altered RNA polymerase that was resistant to the drug in vitro. By separation and mixed reconstitution of core and sigma fractions of mutant and wild-type RNA polymerase, we showed that lipiarmycin resistance in one mutant strain was a property of the core fraction. Genetic mapping experiments indicated that at least two lpm mutants are located between loci determining rifampin resistance and streptolydigin resistance.

Citing Articles

Stabilizing Pseudouridimycin: Synthesis, RNA Polymerase Inhibitory Activity, and Antibacterial Activity of Dipeptide-Modified Analogues.

Anwar A, Cain C, Garza M, Degen D, Ebright R, Del Valle J ChemMedChem. 2023; 19(1):e202300474.

PMID: 37751316 PMC: 10843019. DOI: 10.1002/cmdc.202300474.

RNA polymerases from low G+C gram-positive bacteria.

Miller M, Oakley A, Lewis P Transcription. 2021; 12(4):92-102.

PMID: 34403307 PMC: 8632073. DOI: 10.1080/21541264.2021.1964328.

Semisynthetic Analogs of the Antibiotic Fidaxomicin-Design, Synthesis, and Biological Evaluation.

Dorst A, Berg R, Gertzen C, Schafle D, Zerbe K, Gwerder M ACS Med Chem Lett. 2020; 11(12):2414-2420.

PMID: 33329763 PMC: 7734799. DOI: 10.1021/acsmedchemlett.0c00381.

Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3).

Lin W, Das K, Degen D, Mazumder A, Duchi D, Wang D Mol Cell. 2018; 70(1):60-71.e15.

PMID: 29606590 PMC: 6205224. DOI: 10.1016/j.molcel.2018.02.026.

Antibacterials Developed to Target a Single Organism: Mechanisms and Frequencies of Reduced Susceptibility to the Novel Anti-Clostridium difficile Compounds Fidaxomicin and LFF571.

Leeds J Cold Spring Harb Perspect Med. 2016; 6(2):a025445.

PMID: 26834162 PMC: 4743069. DOI: 10.1101/cshperspect.a025445.

References

Fox T, Pero J . New phage-SPO1-induced polypeptides associated with Bacillus subtilis RNA polymerase. Proc Natl Acad Sci U S A. 1974; 71(7):2761-5. PMC: 388550. DOI: 10.1073/pnas.71.7.2761. View

Sonenshein A, Cami B, Brevet J, Cote R . Isolation and characterization of rifampin-resistant and streptolydigin-resistant mutants of Bacillus subtilis with altered sporulation properties. J Bacteriol. 1974; 120(1):253-65. PMC: 245758. DOI: 10.1128/jb.120.1.253-265.1974. View

Clark S, Losick R, Pero J . New RNA polymerase from Bacillus subtilis infected with phage PBS2. Nature. 1974; 252(5478):21-4. DOI: 10.1038/252021a0. View

Shorenstein R, Losick R . Purification and properties of the sigma subunit of ribonucleic acid polymerase from vegetative Bacillus subtilis. J Biol Chem. 1973; 248(17):6163-9. View

Price A, Frabotta M . Resistance of bacteriophage PBS2 infection to rifampicin, an inhibitor of Bacillus subtilis RNA synthesis. Biochem Biophys Res Commun. 1972; 48(6):1578-85. DOI: 10.1016/0006-291x(72)90894-7. View

CORONELLI C, White R, LANCINI G, Parenti F . Lipiarmycin, a new antibiotic from Actinoplanes. II. Isolation, chemical, biological and biochemical characterization. J Antibiot (Tokyo). 1975; 28(4):253-9. DOI: 10.7164/antibiotics.28.253. View

Hayward R, Scaife J . Systematic nomenclature for the RNA polymerase genes of prokaryotes. Nature. 1976; 260(5552):646-8. DOI: 10.1038/260646a0. View

Tjian R, Stinchcomb D, Losick R . Antibody directed against Bacillus subtilis rho factor purified by sodium dodecyl sulfate slab gel electrophoresis. Effect on transcription by RNA polymerase in crude extracts of vegetative and sporulating cells. J Biol Chem. 1975; 250(22):8824-8. View

Pero J, Nelson J, Fox T . Highly asymmetric transcription by RNA polymerase containing phage-SP01-induced polypeptides and a new host protein. Proc Natl Acad Sci U S A. 1975; 72(4):1589-93. PMC: 432583. DOI: 10.1073/pnas.72.4.1589. View

10.

Talpaert M, Campagnari F, Clerici L . Lipiarmycin: an antibiotic inhibiting nucleic acid polymerases. Biochem Biophys Res Commun. 1975; 63(1):328-34. DOI: 10.1016/s0006-291x(75)80047-7. View

11.

Linn T, Losick R, Sonenshein A . Rifampin resistance mutation of Bacillus subtilis altering the electrophoretic mobility of the beta subunit of ribonucleic acid polymerase. J Bacteriol. 1975; 122(3):1387-90. PMC: 246195. DOI: 10.1128/jb.122.3.1387-1390.1975. View

12.

Sergio S, Pirali G, White R, Parenti F . Lipiarmycin, a new antibiotic from Actinoplanes III. Mechanism of action. J Antibiot (Tokyo). 1975; 28(7):543-9. DOI: 10.7164/antibiotics.28.543. View

13.

Tjian R, Losick R, Pero J, Hinnebush A . Purification and comparative properties of the delta and sigma subunits of RNA polymerase from Bacillus subtilis. Eur J Biochem. 1977; 74(1):149-54. DOI: 10.1111/j.1432-1033.1977.tb11376.x. View

14.

Pero J, Tjian R, Nelson J, Losick R . In vitro transcription of a late class of phage SP01 genes. Nature. 1975; 257(5523):248-51. DOI: 10.1038/257248a0. View

15.

Rima B, Takahashi I . The synthesis of nucleic acids in Bacillus subtilis infected with phage PBS 1. Can J Biochem. 1973; 51(9):1219-24. DOI: 10.1139/o73-161. View

16.

Sonenshein A, Losick R . RNA polymerase mutants blocked in sporulation. Nature. 1970; 227(5261):906-9. DOI: 10.1038/227906a0. View

17.

Kennett R, Sueoka N . Gene expression during outgrowth of Bacillus subtilis spores. The relationship between gene order on the chromosome and temporal sequence of enzyme synthesis. J Mol Biol. 1971; 60(1):31-44. DOI: 10.1016/0022-2836(71)90445-1. View

18.

Losick R, Sonenshein A . Change in the template specificity of RNA polymerase during sporulation of Bacillus subtilis. Nature. 1969; 224(5214):35-7. DOI: 10.1038/224035a0. View

19.

Sonenshein A, Roscoe D . The course of phage phi-e infection in sporulating cells of Bacillus subtilis strain 3610. Virology. 1969; 39(2):265-75. DOI: 10.1016/0042-6822(69)90047-6. View

20.

Parenti F, PAGANI H, Beretta G . Lipiarmycin, a new antibiotic from Actinoplanes. I. Description of the producer strain and fermentation studies. J Antibiot (Tokyo). 1975; 28(4):247-52. DOI: 10.7164/antibiotics.28.247. View