Evolved neomycin phosphotransferase from an isolate of Klebsiella pneumoniae

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Abstract
Summary: A new aminoglycoside resistance gene (aphA 1‐IA6) confers high‐level resistance to neomycin. The sequence of apA 1‐IAB is closely related to aphA 1 found in the transposons Tn4352, 7n903 and Tn602. For example, aphA 1‐IAB differs from aphA 1–903 at five nucleotides that result in four amino acid replacements. The enzyme encoded by aphA 1‐IAB has a significantly higher turnover number with neomycin, kanamycin and G418 as substrates than does the aphA 1–903 enzyme. A parsimonious phylogenetic tree suggests that aphA 1‐IAB evolved from an ancestral form that is closely related or identical to the aphA 1 found in Tn903. The excess of replacement substitutions over silent substitutions in aphA I‐IAB, as well as its convergence toward aphA 3 from Staphylococcus aureus, is indicative of selective evolution. Our hypothesis to explain these results is that aphA 1‐IAB evolved under the selective pressure of neomycin use in relatively recent times.