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Mechanisms of Resistance

Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae

Shoji Seyama, Takeaki Wajima, Hidemasa Nakaminami, Norihisa Noguchi
Shoji Seyama
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
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Takeaki Wajima
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
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Hidemasa Nakaminami
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
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Norihisa Noguchi
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
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DOI: 10.1128/AAC.01337-17
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  • TABLE 1

    Characteristics and MICs of bacterial strains used in this study

    StrainSerotypeSTDeletion site in acrRMIC (μg/ml)a
    CLRCLR + CCCPAZMAZM + CCCPEB
    0.75 μg/ml CCCP1.5 μg/ml CCCP0.75 μg/ml CCCP1.5 μg/ml CCCP
    2012-42NTb156Nucleotide 141c32164841≥16
    2011-70NT156Nucleotide 141c32161410.258
    RdNT47Nonec840.2510.5≤0.061
    Rd42acrNT47Nucleotide 141c32162840.58
    Rd70acrNT47Nucleotide 14132161420.134
    • ↵a CLR, clarithromycin; AZM, azithromycin; EB, ethidium bromide; CCCP, carbonyl cyanide m-chlorophenylhydrazone.

    • ↵b NT, nontypeable.

    • ↵c Results of a previous study by Seyama et al. (5).

  • TABLE 2

    Detailed MICs of H. influenzae strain Rd and strains with acr mutations

    StrainRelative acrB mRNA levelaMIC (μg/ml)Ratiob
    CLRAZMCLRAZM
    Rd0.82 ± 0.248111
    Rd42acr1.86 ± 0.35c3083.88
    Rd70acr1.45 ± 0.09c263.53.33.5
    • ↵a The transcription levels were calculated in comparison with the gyrB transcription level. The measurements of acrB transcription levels were performed at least three times on independent occasions.

    • ↵b Ratio of each MIC to that of H. influenzae Rd.

    • ↵c P < 0.05, Rd versus Rd42acr and Rd versus Rd70acr.

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      Supplemental Figures S1 and S2

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Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae
Shoji Seyama, Takeaki Wajima, Hidemasa Nakaminami, Norihisa Noguchi
Antimicrobial Agents and Chemotherapy Oct 2017, 61 (11) e01337-17; DOI: 10.1128/AAC.01337-17

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Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae
Shoji Seyama, Takeaki Wajima, Hidemasa Nakaminami, Norihisa Noguchi
Antimicrobial Agents and Chemotherapy Oct 2017, 61 (11) e01337-17; DOI: 10.1128/AAC.01337-17
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KEYWORDS

azithromycin
Bacterial Proteins
Drug Resistance, Bacterial
Haemophilus influenzae
BLNAR
azithromycin low susceptibility
AcrR
AcrB

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