Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

doi:10.1128/AAC.01336-17

. 2017 Sep 22;61(10):e01336-17.

doi: 10.1128/AAC.01336-17. Print 2017 Oct.

Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

Kageto Yamada^{1

2}, Ryoichi Saito³, Saori Muto², Machiko Kashiwa², Yoshiko Tamamori², Shingo Fujisaki⁴

Affiliations

¹ Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan kageto_yamada@tokyo-hmt.jp.
² Department of Clinical Laboratory, Tokyo Metropolitan Health and Medical Treatment Corporation Toshima Hospital, Tokyo, Japan.
³ Department of Microbiology and Immunology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.

PMID: 28760904
PMCID: PMC5610493
DOI: 10.1128/AAC.01336-17

Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

Kageto Yamada et al. Antimicrob Agents Chemother. 2017.

. 2017 Sep 22;61(10):e01336-17.

doi: 10.1128/AAC.01336-17. Print 2017 Oct.

Authors

Kageto Yamada^{1

2}, Ryoichi Saito³, Saori Muto², Machiko Kashiwa², Yoshiko Tamamori², Shingo Fujisaki⁴

Affiliations

¹ Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan kageto_yamada@tokyo-hmt.jp.
² Department of Clinical Laboratory, Tokyo Metropolitan Health and Medical Treatment Corporation Toshima Hospital, Tokyo, Japan.
³ Department of Microbiology and Immunology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.

PMID: 28760904
PMCID: PMC5610493
DOI: 10.1128/AAC.01336-17

Abstract

Moraxella catarrhalis causes respiratory infections. In this study, fluoroquinolone-resistant strains were selected in vitro to evaluate the mechanism of fluoroquinolone resistance. Strains with reduced fluoroquinolone susceptibility were obtained by stepwise selection in levofloxacin, and fluoroquinolone targets gyr and par were sequenced. Six novel mutations in GyrA (D84Y, T594dup, and A722dup), GyrB (E479K and D439N), and ParE (Q395R) involved in M. catarrhalis resistance to fluoroquinolones were revealed.

Keywords: Moraxella catarrhalis; fluoroquinolone; gyr; par; quinolone resistance-determining region.

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Figures

**FIG 1**
Position of the primers and mutations within the *gyr* and *par* genes of Moraxella catarrhalis. Dotted arrows denote sequencing primers. Solid arrows indicate primers that were used for both PCR (for direct sequencing and transformation) and sequencing.

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References

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1. Saito R, Nonaka S, Fujinami Y, Matsuoka S, Nakajima S, Nishiyama H, Okamura N. 2014. The frequency of BRO β-lactamase and its relationship to antimicrobial susceptibility and serum resistance in Moraxella catarrhalis. J Infect Chemother 20:6–8. doi:10.1016/j.jiac.2013.06.003. - DOI - PubMed
1. Schmitz FJ, Beeck A, Perdikouli M, Boos M, Mayer S, Scheuring S, Köhrer K, Verhoef J, Fluit AC. 2002. Production of BRO β-lactamases and resistance to complement in European Moraxella catarrhalis isolates. J Clin Microbiol 40:1546–1548. doi:10.1128/JCM.40.4.1546-1548.2002. - DOI - PMC - PubMed
1. Khan MA, Northwood JB, Levy F, Verhaegh SJ, Farrell DJ, Van Belkum A, Hays JP. 2010. bro β-lactamase and antibiotic resistance in a global cross-sectional study of Moraxella catarrhalis from children and adults. J Antimicrob Chemother 65:91–97. doi:10.1093/jac/dkp401. - DOI - PubMed
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[1] Murphy TF, Parameswaran GI. 2009. Moraxella catarrhalis, a human respiratory tract pathogen. Clin Infect Dis 49:124–131. doi:10.1086/599375. - DOI - PubMed

[2] Murphy TF, Parameswaran GI. 2009. Moraxella catarrhalis, a human respiratory tract pathogen. Clin Infect Dis 49:124–131. doi:10.1086/599375. - DOI - PubMed

[3] Saito R, Nonaka S, Fujinami Y, Matsuoka S, Nakajima S, Nishiyama H, Okamura N. 2014. The frequency of BRO β-lactamase and its relationship to antimicrobial susceptibility and serum resistance in Moraxella catarrhalis. J Infect Chemother 20:6–8. doi:10.1016/j.jiac.2013.06.003. - DOI - PubMed

[4] Saito R, Nonaka S, Fujinami Y, Matsuoka S, Nakajima S, Nishiyama H, Okamura N. 2014. The frequency of BRO β-lactamase and its relationship to antimicrobial susceptibility and serum resistance in Moraxella catarrhalis. J Infect Chemother 20:6–8. doi:10.1016/j.jiac.2013.06.003. - DOI - PubMed

[5] Schmitz FJ, Beeck A, Perdikouli M, Boos M, Mayer S, Scheuring S, Köhrer K, Verhoef J, Fluit AC. 2002. Production of BRO β-lactamases and resistance to complement in European Moraxella catarrhalis isolates. J Clin Microbiol 40:1546–1548. doi:10.1128/JCM.40.4.1546-1548.2002. - DOI - PMC - PubMed

[6] Schmitz FJ, Beeck A, Perdikouli M, Boos M, Mayer S, Scheuring S, Köhrer K, Verhoef J, Fluit AC. 2002. Production of BRO β-lactamases and resistance to complement in European Moraxella catarrhalis isolates. J Clin Microbiol 40:1546–1548. doi:10.1128/JCM.40.4.1546-1548.2002. - DOI - PMC - PubMed

[7] Khan MA, Northwood JB, Levy F, Verhaegh SJ, Farrell DJ, Van Belkum A, Hays JP. 2010. bro β-lactamase and antibiotic resistance in a global cross-sectional study of Moraxella catarrhalis from children and adults. J Antimicrob Chemother 65:91–97. doi:10.1093/jac/dkp401. - DOI - PubMed

[8] Khan MA, Northwood JB, Levy F, Verhaegh SJ, Farrell DJ, Van Belkum A, Hays JP. 2010. bro β-lactamase and antibiotic resistance in a global cross-sectional study of Moraxella catarrhalis from children and adults. J Antimicrob Chemother 65:91–97. doi:10.1093/jac/dkp401. - DOI - PubMed

[9] Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. 2005. Quinolones in 2005: an update. Clin Microbiol Infect 11:256–280. doi:10.1111/j.1469-0691.2005.01131.x. - DOI - PubMed

[10] Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. 2005. Quinolones in 2005: an update. Clin Microbiol Infect 11:256–280. doi:10.1111/j.1469-0691.2005.01131.x. - DOI - PubMed

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Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

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Molecular Characterization of Fluoroquinolone-Resistant Moraxella catarrhalis Variants Generated In Vitro by Stepwise Selection

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