title: The VanRS Homologous Two-Component System VnlRSAb of the Glycopeptide Producer Amycolatopsis balhimycina Activates Transcription of the vanHAXSc Genes in Streptomyces coelicolor, but not in A. balhimycina.
abstract: In enterococci and in Streptomyces coelicolor, a glycopeptide nonproducer, the glycopeptide resistance genes vanHAX are colocalized with vanRS. The two-component system (TCS) VanRS activates vanHAX transcription upon sensing the presence of glycopeptides. Amycolatopsis balhimycina, the producer of the vancomycin-like glycopeptide balhimycin, also possesses vanHAXAb genes. The genes for the VanRS-like TCS VnlRSAb, together with the carboxypeptidase gene vanYAb, are part of the balhimycin biosynthetic gene cluster, which is located 2 Mb separate from the vanHAXAb. The deletion of vnlRSAb did not affect glycopeptide resistance or balhimycin production. In the A. balhimycina vnlRAb deletion mutant, the vanHAXAb genes were expressed at the same level as in the wild type, and peptidoglycan (PG) analyses proved the synthesis of resistant PG precursors. Whereas vanHAXAb expression in A. balhimycina does not depend on VnlRAb, a VnlRAb-depending regulation of vanYAb was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) and RNA-seq analyses. Although VnlRAb does not regulate the vanHAXAb genes in A. balhimycina, its heterologous expression in the glycopeptide-sensitive S. coelicolor ΔvanRSSc deletion mutant restored glycopeptide resistance. VnlRAb activates the vanHAXSc genes even in the absence of VanS. In addition, expression of vnlRAb increases actinorhodin production and influences morphological differentiation in S. coelicolor.
authors.affiliation: 1 Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology/Biotechnology, University of Tuebingen , Tuebingen, Germany .
authors.forename: Regina
authors.initials: R
authors.lastname: Kilian
authors.affiliation: 1 Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology/Biotechnology, University of Tuebingen , Tuebingen, Germany .
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Frasch
authors.affiliation: 1 Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology/Biotechnology, University of Tuebingen , Tuebingen, Germany .
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.affiliation: 1 Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology/Biotechnology, University of Tuebingen , Tuebingen, Germany .|2 German Centre for Infection Research (DZIF) , Partner Site Tuebingen, Tuebingen, Germany .
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: 1 Interfaculty Institute of Microbiology and Infection Medicine Tuebingen, Microbiology/Biotechnology, University of Tuebingen , Tuebingen, Germany .|2 German Centre for Infection Research (DZIF) , Partner Site Tuebingen, Tuebingen, Germany .
authors.forename: Evi
authors.initials: E
authors.lastname: Stegmann
mesh_terms: D000192:Actinomycetales / Q000235:genetics* / Q000378:metabolism; D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D002874:Chromosome Mapping; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005810:Multigene Family; D010457:Peptidoglycan / Q000096:biosynthesis / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014640:Vancomycin / Q000031:analogs & derivatives / Q000096:biosynthesis; D020713:Vancomycin Resistance / Q000235:genetics; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010457:Peptidoglycan; D014640:Vancomycin; C087127:balhimycin; C013390:actinorhodin; D000095622:Benzoisochromanequinones