Evolved neomycin phosphotransferase from an isolate of Klebsiella pneumoniae

Mol Microbiol. 1991 Aug;5(8):2039-46. doi: 10.1111/j.1365-2958.1991.tb00826.x.


A new aminoglycoside resistance gene (aphA1-IAB) confers high-level resistance to neomycin. The sequence of aphA1-IAB is closely related to aphA1 found in the transposons Tn4352, Tn903 and Tn602. For example, aphA1-IAB differs from aphA1-903 at five nucleotides that result in four amino acid replacements. The enzyme encoded by aphA1-IAB has a significantly higher turnover number with neomycin, kanamycin and G418 as substrates than does the aphA1-903 enzyme. A parsimonious phylogenetic tree suggests that aphA1-IAB evolved from an ancestral form that is closely related or identical to the aphA1 found in Tn903. The excess of replacement substitutions over silent substitutions in aphA1-IAB, as well as its convergence toward aphA3 from Staphylococcus aureus, is indicative of selective evolution. Our hypothesis to explain these results is that aphA1-IAB evolved under the selective pressure of neomycin use in relatively recent times.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Biological Evolution
  • Blotting, Western
  • DNA Transposable Elements / genetics
  • Drug Resistance, Microbial
  • Kanamycin / metabolism
  • Kanamycin / pharmacology
  • Kanamycin Kinase
  • Kinetics
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / genetics
  • Molecular Sequence Data
  • Neomycin / metabolism*
  • Neomycin / pharmacology
  • Phosphotransferases / chemistry
  • Phosphotransferases / genetics*
  • Plasmids / genetics
  • Sequence Homology, Nucleic Acid*
  • Staphylococcus aureus / genetics
  • Temperature


  • DNA Transposable Elements
  • Kanamycin
  • Phosphotransferases
  • Kanamycin Kinase
  • Neomycin

Associated data

  • GENBANK/S75769
  • GENBANK/X52368
  • GENBANK/X52369
  • GENBANK/X52370
  • GENBANK/X52371
  • GENBANK/X52372
  • GENBANK/X60543
  • GENBANK/X65133
  • GENBANK/X65134
  • GENBANK/X65135