A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii

Mol Microbiol. 1998 Jun;28(6):1345-53. doi: 10.1046/j.1365-2958.1998.00900.x.

Abstract

A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Alleles
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Blotting, Northern
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Microbial / genetics
  • Drug Resistance, Multiple / genetics*
  • Escherichia coli Proteins*
  • Gene Expression Regulation, Bacterial*
  • Genes, Bacterial*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation
  • Plasmids / genetics
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Providencia / drug effects
  • Providencia / genetics*
  • Providencia / metabolism
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Trans-Activators / metabolism
  • Transcription, Genetic

Substances

  • AarP protein, Providencia stuartii
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • MarA protein, E coli
  • PhoQ protein, Bacteria
  • RNA, Messenger
  • Trans-Activators
  • Acetyltransferases
  • aminoglycoside 2'-N-acetyltransferase
  • Protein Kinases
  • AarG protein, Providencia stuartii

Associated data

  • GENBANK/AF041833