title: Distamycin A selectively inhibits Acanthamoeba RNA synthesis and differentiation.
abstract: The effects of distamycin A on Acanthamoeba transcription, growth and differentiation were determined. Distamycin A inhibits transcription both in vitro and in vivo and can displace from DNA the transcription activator TATA binding protein promoter binding factor (TPBF). Inhibition in vivo is surprisingly selective for large rRNA precursors, 5S rRNA, profilin, S-adenosylmethionine synthetase, and extendin. Transcription from the TATA binding protein (TBP), TPBF, protein disulfide isomerase, tubulin and RNA polymerase II large subunit genes is only slightly inhibited. Moreover the rate of 5S rRNA transcription eventually recovers and exceeds that of untreated cells, while profilin transcription remains inhibited. Distamycin A inhibition is accompanied by a complex pattern of alterations to steady state levels of mRNAs. Actin, profilin and S-adenosylmethionine synthetase mRNAs are degraded, whereas mRNA encoding TBP is increased slightly in abundance. Transcription inhibition is accompanied by cessation of growth and severe morphological changes to Acanthamoeba, which are consistent with loss of production of mRNA encoding cytoskeletal proteins. Distamycin A also prevents starvation-induced differentiation of Acanthamoeba, in part due to complete prevention of cellulose production and cell wall formation.
authors.affiliation: Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington 05405, USA.
authors.forename: T
authors.initials: T
authors.lastname: Orfeo
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Ward
authors.forename: E
authors.initials: E
authors.lastname: Bateman
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002482:Cellulose / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004214:Distamycins / Q000494:pharmacology*; D017125:Genes, Protozoan / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D016053:RNA, Protozoan / Q000096:biosynthesis*; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D004214:Distamycins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D035181:TATA-Box Binding Protein; C097052:TPBF protein, Acanthamoeba castellanii; D015534:Trans-Activators; D014157:Transcription Factors; C030000:stallimycin; D002482:Cellulose