Detection of a Novel aph(2") Allele ( aph[2"]-Ie ) Conferring High-Level Gentamicin Resistance and a Spectinomycin Resistance Gene ant(9)-Ia ( aad9 ) in Clinical Isolates of Enterococci

Department of Hygiene, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
Microbial Drug Resistance (Impact Factor: 2.49). 02/2005; 11(3):239-47. DOI: 10.1089/mdr.2005.11.239
Source: PubMed


Aminoglycoside-modifying enzymes (AMEs) are major factors that confer aminoglycoside resistance to enterococci. In an epidemiologic study on distribution of 12 AME genes in 534 recent clinical strains isolated from a Japanese hospital, two uncommon AME genes, ant(9)-Ia and a novel aph(2") allele, aph(2")-Ie, were detected. ant(9)-Ia had been reported only in Staphylococcus aureus and encodes spectinomycin adenylyltransferase ANT(9)-I, which confers resistance to spectinomycin. The ant(9)-Ia gene was detected in three strains, a single strain each of Enterococcus faecalis, E. faecium, and E. avium. Nucleotide sequences of ant(9)-Ia from these three enterococcal species were identical to that reported for S. aureus and considered to be located on Tn 554. The new aph(2") allele, designated aph(2")-Ie, was identified in three E. faecium strains. The aph(2")-Ie allele was genetically close to aph(2")-Id reported in E. casseliflavus (93.7% amino acid sequence identity; 96.3% similarity), while distant from aph(2")-Ia, aph(2")-Ib, or aph(2")-Ic (26.3-29.5% amino acid sequence identity). Sequence divergence between APH(2")-Id and APH(2")-Ie was mostly located in amino-terminal half. In contrast, sequences corresponding to the three motifs required for aminoglycoside phosphotransferase were conserved except for a single amino acid. Three E. faecium strains having aph(2")-Ie showed high-level resistance to gentamicin and streptomycin, but not to kanamycin, dibekacin, and tobramycin, unlike enzyme specificity described for aph(2")-Id in E. casseliflavus. Such a difference in resistance phenotype was suggested to be related to amino acid sequence divergence between APH(2")-Id and APH(2")-Ie.

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    • "It is the most prevalent form of acquired gentamicin resistance in both species and associated with homologues of transposon Tn4001/Tn5281 flanked by two copies of IS256 and most probably originating from staphylococci (Casetta et al., 1998; Hallgren et al., 2003; Saeedi et al., 2004). Gentamicin resistance may also be encoded by other determinants such as aac(6')-Ii, aph(2 " )-Ie, and ant(6)- Ia (Jackson et al., 2004; Jackson et al., 2005; Zarrilli et al., 2005; Mahbub et al., 2005). High-level streptomycin resistance is encoded by the aadE gene which is an integral part of a multiresistance gene cluster aadE-sat4-aphA encoding streptomycin-streptothricin-kanamycin resistance. "

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