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Mechanisms of Resistance

Ribosomal Mutations as the Main Cause of Macrolide Resistance in Campylobacter jejuni and Campylobacter coli

Mirva Lehtopolku, Pirkko Kotilainen, Marjo Haanperä-Heikkinen, Ulla-Maija Nakari, Marja-Liisa Hänninen, Pentti Huovinen, Anja Siitonen, Erkki Eerola, Jari Jalava, Antti J. Hakanen
Mirva Lehtopolku
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
2Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
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  • For correspondence: mipleht@utu.fi
Pirkko Kotilainen
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
2Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
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Marjo Haanperä-Heikkinen
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
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Ulla-Maija Nakari
3Bacteriology Unit, National Institute for Health and Welfare (THL), Turku and Helsinki, Finland
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Marja-Liisa Hänninen
4Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
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Pentti Huovinen
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
5Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
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Anja Siitonen
3Bacteriology Unit, National Institute for Health and Welfare (THL), Turku and Helsinki, Finland
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Erkki Eerola
5Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
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Jari Jalava
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
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Antti J. Hakanen
1Antimicrobial Resistance Unit, Turku and Helsinki, Finland
2Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
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DOI: 10.1128/AAC.00314-11
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Tables

  • Table 1.

    Ribosomal mutations and erythromycin susceptibility in Campylobacter jejuni strains compared to C. jejuni DSM 4688 type straine

    Strain(s)Erythromycin MIC (μg/ml)d23S rRNA gene mutationaL4 mutation(s)L22 mutation(s)L22 insertion
    DSM 4688b0.5
    1>128wtA121V, I192MA74G, A109T, E111A, T114A, A130T, A132V, A141V, K144E73-GAVLT-74
    2–6>128A2059GA121V, I192MA74G, A109T, E111A, T114A, A130T, A132V, A141V, K144E
    7>128A2059GwtA74G, A103V, A141V, K144E
    8c>128A2059GwtA74G, A103V, A141V
    9, 10>128A2059GA121V, I192M, A196VV65I, A109S, A143V
    11>128A2059GA121V, I192MQ24R, V65I, A143V
    12>128A2059GA121V, I192MV65I, A103V
    13>128A2059GA121V, I192MG86E
    14128A2059GA121V, I192MA74G, A109T, E111A, T114A, A130T, A132V, A141V, K144E
    15128A2059GwtV65I, A103V
    1664wtT177SI65V, D72N
    17, 188wtA121V, I192MQ24R, V65I, A143V
    198wtA121V, I192MV65I, A109S, A143V
    20, 224–8wtA121V, I192MV65I, A103V
    214wtN95S, A121V, I192MQ24R, V65I, A143V
    232wrA129T, T201Iwt
    24, 251wtA121V, I192MV65I, A109S, A143V
    26, 30, 310.5–1wtA121V, I192M, A196VV65I, A109S, A143V
    271wtwtV65I, A103V
    28, 291wtT177SV65I
    320.5wtV80I, A121V, I192MV65I, A103V
    330.5wtS132N, T177SV65I
    340.5wtA140Twt
    • ↵a Position according to Escherichia coli numbering.

    • ↵b Reference strain for the ribosomal proteins L4 and L22.

    • ↵c Only two mutated copies of A2059G.

    • ↵d From each MIC, a number of strains were selected for the efflux pump inhibitor (NMP and PAβN) testing, and no decrease in MIC was observed.

    • ↵e Abbreviations: A, Ala; D, Asp; E, Glu; G, Gly; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; wt, wild type, based on corresponding sequences of C. jejuni DSM 4688 type strain.

  • Table 2.

    Ribosomal mutations and erythromycin susceptibility in Campylobacter coli strains compared to C. coli DSM 4689 type straine

    Strain(s)Erythromycin MIC (μg/ml)23S rRNA gene mutationaL4 mutation(s)L22 mutation(s)L22 insertions
    DSM 4689b0.5wt
    36>128A2059GS28P, T176Swt
    41,c 37–40, 42–44>128A2059GS28Pwt
    45>128A2059GS28P, V121A, M192Iwt
    46, 47>128A2059GS28P, V121A, V176I, T177S, V184I, M192IA103V
    48>128A2059GS28PG58S
    49>128A2059GS28P, M192IT95I, A103V, T109A, A111E, A114T, V121A119-TTTKA-120, 124-T-125
    50>128A2059GS28P, M192IA103V, T109A, A111E, A114T, V121A119-TTTKA-120, 124-T-125
    51d128A2059GS28P, V121A, M192IA103V, T109A, A111E, A114T, V121A119-TTTKA-120, 124-T-125
    5216wtS28Pwt
    538wtS28P, V121A, V176I, T177S, V184I, M192IA103V
    548wtS28P, M192IA103V, T109A, A111E, A114T, V121A119-TTTKA-120, 124-T-125
    • ↵a Position according to Escherichia coli numbering.

    • ↵b Reference strain for the ribosomal proteins L4 and L22.

    • ↵c Only two mutated copies of A2059G.

    • ↵d NMP caused 2-fold decrease in MIC.

    • ↵e Abbreviations: A, Ala; E, Glu; G, Gly; I, Ile; K, Lys; M, Met; P, Pro; S, Ser; T, Thr; V, Val; wt, wild type, based on corresponding sequences of C. coli DSM 4689 type strain. One strain from each row was selected for the efflux pump inhibitor (NMP and PAβN) testing, and only one strain exhibited a 2-fold decrease in MIC.

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Ribosomal Mutations as the Main Cause of Macrolide Resistance in Campylobacter jejuni and Campylobacter coli
Mirva Lehtopolku, Pirkko Kotilainen, Marjo Haanperä-Heikkinen, Ulla-Maija Nakari, Marja-Liisa Hänninen, Pentti Huovinen, Anja Siitonen, Erkki Eerola, Jari Jalava, Antti J. Hakanen
Antimicrobial Agents and Chemotherapy Nov 2011, 55 (12) 5939-5941; DOI: 10.1128/AAC.00314-11

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Ribosomal Mutations as the Main Cause of Macrolide Resistance in Campylobacter jejuni and Campylobacter coli
Mirva Lehtopolku, Pirkko Kotilainen, Marjo Haanperä-Heikkinen, Ulla-Maija Nakari, Marja-Liisa Hänninen, Pentti Huovinen, Anja Siitonen, Erkki Eerola, Jari Jalava, Antti J. Hakanen
Antimicrobial Agents and Chemotherapy Nov 2011, 55 (12) 5939-5941; DOI: 10.1128/AAC.00314-11
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