title: Impairing methylations at ribosome RNA, a point mutation-dependent strategy for aminoglycoside resistance: the rsmG case.
abstract: BACKGROUND
  Aminoglycosides like streptomycin are well-known for binding at specific regions of ribosome RNA and then acting as translation inhibitors. Nowadays, several pathogens have been detected to acquire an undefined strategy involving mutation at non structural ribosome genes like those acting as RNA methylases. rsmG is one of those genes which encodes an AdoMet-dependent methyltransferase responsible for the synthesis of m 7 G527 in the 530 loop of bacterial 16S rRNA. This loop is universally conserved, plays a key role in ribosomal accuracy, and is a target for streptomycin binding. Loss of the m 7 G527 modification confers low-level streptomycin resistance and may affect ribosomal functioning.
  
  
  OBJECTIVE
  After taking into account genetic information indicating that some clinical isolates of human pathogens show streptomycin resistance associated with mutations at rsmG , we decided to explore new hot spots for mutation capable of impairing the RsmG in vivo function and of promoting low-level streptomycin resistance.
  
  
  METHODS
  To gain insights into the molecular and genetic mechanism of acquiring this aminoglycoside resistance phenotype and the emergence of high-level streptomycin resistance in rsmG mutants, we mutated Escherichia coli rsmG and also performed a genotyping study on rpsL from several isolates showing the ability to grow at higher streptomycin concentrations than parental strains.
  
  
  RESULTS
  We found that the mutations at rpsL were preferentially present in these mutants, and we observed a clear synergy between rsmG and rpsL genes to induce streptomycin resistance.
  
  
  CONCLUSIONS
  We contribute to understand a common mechanism that is probably transferable to other ribosome RNA methylase genes responsible for modifications at central sites for ribosome function.
authors: Grupo de Análisis Bioinformático, GABi, Centro de Investigación y Desarrollo en Biotecnología, CIDBIO, Bogotá, D.C, Colombia.
authors: Alfonso
authors: A
authors: Benítez-Páez
authors: Grupo de Análisis Bioinformático, GABi, Centro de Investigación y Desarrollo en Biotecnología, CIDBIO, Bogotá, D.C, Colombia.
authors: Sonia
authors: S
authors: Cárdenas-Brito
authors: Grupo de Genética y Bioquímica de Microorganismos, GEBIOMIC, Universidad de Antioquia, Medellín, Colombia.
authors: Mauricio
authors: M
authors: Corredor
authors: Laboratorio de Modificación de ARN y Enfermedades Mitocondriales, Centro de Investigación Príncipe Felipe.
authors: Magda
authors: M
authors: Villarroya
authors: Laboratorio de Modificación de ARN y Enfermedades Mitocondriales, Centro de Investigación Príncipe Felipe.
authors: María Eugenia
authors: ME
authors: Armengod
mesh_terms: D000595:Amino Acid Sequence; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D017354:Point Mutation; D011487:Protein Conformation; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013307:Streptomycin / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D011993:Recombinant Fusion Proteins; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; C000717190:RpsI protein, E coli; C506766:RpsL protein, E coli; D012436:S-Adenosylmethionine; C457299:GidB protein, E coli; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D013307:Streptomycin