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Identification of Aminoglycoside-Modifying Enzymes by Susceptibility Testing: Epidemiology of Methicillin-Resistant Staphylococcus aureus in Japan
Abstract
A multiple-primer PCR was used to identify genes encoding aminoglycoside-modifying enzymes in 381 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The technique used three sets of primers delineating specific DNA fragments of the aph(3′)-III, ant(4′)-I , and aac(6′)-aph(2") genes, which influence the MICs of gentamicin, tobramycin, and lividomycin. Isolates with none of the three genes detected were susceptible to all three agents. Isolates with the aph(3′)-III gene showed resistance to lividomycin (MIC > 1,024 μg/ml), and those with the ant(4′)-I gene were resistant to tobramycin (MIC ≥ 8 μg/ml). Isolates with only the aac(6′)-aph(2") gene were resistant to gentamicin (MIC ≥ 8 μg/ml) and tobramycin in decreasing order; those with both the ant(4′)-I and aac(6′)-aph(2") genes also were resistant to gentamicin and tobramycin, but in increasing order. Susceptibility testing, then, could detect specific genes. In 381 Japanese MRSA isolates, the ant(4′)-I, aac(6′)-aph(2") , and aph(3′)-III genes were prevalent in 84.5, 61.7, and 8.9%, respectively. Isolates with only the ant(4′)-I gene had coagulase type II or III, but isolates with both the ant(4′)-I and aac(6′)-aph(2") genes included all coagulase types. Most isolates with coagulase type IV or VII carried the aac(6′)-aph(2") gene. Of the MRSA isolates with ant(4′)-I and/or aac(6′)-aph(2") genes, 97% were resistant to aminoglycosides in clinical use, but a new aminoglycoside, arbekacin, had excellent activity against these isolates.
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“the two-domain acetyltransferase/phosphotransferase AAC(6′)-Ie/APH(2”)-Ia, encoded by the aacA-aphD gene and causing resistance to gentamicin, tobramycin, kanamycin, amikacin and netilmicin”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [141]
In the citing paper
“The most common mechanism of resistance to aminoglycosides in S. aureus is the synthesis of enzymes of the transferase group (Figure 1) [135,140,141,142,143,144].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [141]
In the citing paper
“The MIC of gentamicin for strains that produce this enzyme ranges from 8 mg/L to > 1024 mg/L. The MIC50 of gentamicin determined on a large population of S. aureus strains was 128 mg/L, and the MIC90 was 512 mg/L [141].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [141]
In the citing paper
“Synthesis of AAC(6′)-Ie/APH(2”)-Ia also usually determines resistance to tobramycin. The MIC of tobramycin for strains synthesizing this enzyme, ranges from 8 mg/L to 256 mg/L (MIC50 is 32 mg/L and MIC90 is 64 mg/L) [141].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [141]
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Cited by
Molecular Mechanisms of Drug Resistance in Staphylococcus aureus
Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., & Marusza, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158088 · Cited by 412
Metadata
- Authors
- Ida, T., Okamoto, R., Shimauchi, C., Okubo, T., Kuga, A., & Inoue, M.
- Affiliations
- <!--label omitted: 1-->Department of Microbiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555,1 and
- <!--label omitted: 2-->Laboratory of Drug Resistance in Bacteria, Gunma University School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511,2Japan
- Venue
- Journal of Clinical Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2001-09
- Volume
- 39
- Issue
- 9
- Pages
- 3115-3121
- ISSN
- 0095-1137
- 1098-660X
- Cited by
- 103
- References
- 0
- Language
- en
- Licence
- journals.asm.org/non-commercial-tdm-license (tdm)
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- Ida, T., Okamoto, R., Shimauchi, C., Okubo, T., Kuga, A., & Inoue, M. (2001). Identification of Aminoglycoside-Modifying Enzymes by Susceptibility Testing: Epidemiology of Methicillin-Resistant Staphylococcus aureus in Japan. Journal of Clinical Microbiology. https://doi.org/10.1128/jcm.39.9.3115-3121.2001
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