Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene

Grith Miriam Maigaard Hermansen, Lars Jelsbak

    Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

    Abstract

    Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have identified a novel gene cluster, which is involved in colistin susceptibility in chronically infecting P. aeruginosa strains. The gene cluster contains two uncharacterized glycosyltransferases and a gene of unknown function. During chronic infection of CF patients one of the glycosyltransferase genes is prone to mutation. Methods: The glycosyltransferase single nucleotide polymorphism (SNP) was reverted to the reference genotype in a clinical isolate and in parallel introduced into the laboratory reference strain PAO1 to provide a clear background for mutational analysis. We evaluated minimal inhibitory concentration by microbroth dilution, virulence in an amoebae model and LPS structure by visualization in a silver-stained gel. Results: Reversion of the SNP to reference genotype resulted in increased colistin susceptibility, reduced virulence in an amoebae model and altered LPS structure. The results indicate that this glycosyltransferase polymorphism is needed for the clinical strain to be fully virulent. However, introducing the SNP into PAO1 did not result in altered phenotypes. These results reveal this uncharacterized glycosyltransferase as a novel in vivo path to colistin resistance by LPS modification. Conclusions: Colistin resistance development in vivo occurs via multiple paths. Here a novel pathway for the development of colistin resistance was described. It involves mutations in a hitherto uncharacterized glycosyltransferase.
    Original languageEnglish
    Title of host publicationThe Danish Microbiological Society Annual Congress 2015 : Programme & Abstracts
    Place of PublicationCopenhagen
    Publication date2015
    Pages32-33
    Publication statusPublished - 2015
    EventThe Danish Microbiological Society Annual Congress 2015 - Eigtved's Pakhus, Copenhagen, Denmark
    Duration: 9 Nov 20159 Nov 2015

    Conference

    ConferenceThe Danish Microbiological Society Annual Congress 2015
    LocationEigtved's Pakhus
    CountryDenmark
    CityCopenhagen
    Period09/11/201509/11/2015

    Cite this

    Hermansen, G. M. M., & Jelsbak, L. (2015). Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene. In The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts (pp. 32-33). Copenhagen.
    Hermansen, Grith Miriam Maigaard ; Jelsbak, Lars. / Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene. The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, 2015. pp. 32-33
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    abstract = "Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have identified a novel gene cluster, which is involved in colistin susceptibility in chronically infecting P. aeruginosa strains. The gene cluster contains two uncharacterized glycosyltransferases and a gene of unknown function. During chronic infection of CF patients one of the glycosyltransferase genes is prone to mutation. Methods: The glycosyltransferase single nucleotide polymorphism (SNP) was reverted to the reference genotype in a clinical isolate and in parallel introduced into the laboratory reference strain PAO1 to provide a clear background for mutational analysis. We evaluated minimal inhibitory concentration by microbroth dilution, virulence in an amoebae model and LPS structure by visualization in a silver-stained gel. Results: Reversion of the SNP to reference genotype resulted in increased colistin susceptibility, reduced virulence in an amoebae model and altered LPS structure. The results indicate that this glycosyltransferase polymorphism is needed for the clinical strain to be fully virulent. However, introducing the SNP into PAO1 did not result in altered phenotypes. These results reveal this uncharacterized glycosyltransferase as a novel in vivo path to colistin resistance by LPS modification. Conclusions: Colistin resistance development in vivo occurs via multiple paths. Here a novel pathway for the development of colistin resistance was described. It involves mutations in a hitherto uncharacterized glycosyltransferase.",
    author = "Hermansen, {Grith Miriam Maigaard} and Lars Jelsbak",
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    language = "English",
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    Hermansen, GMM & Jelsbak, L 2015, Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene. in The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, pp. 32-33, The Danish Microbiological Society Annual Congress 2015, Copenhagen, Denmark, 09/11/2015.

    Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene. / Hermansen, Grith Miriam Maigaard; Jelsbak, Lars.

    The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen, 2015. p. 32-33.

    Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

    TY - ABST

    T1 - Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene

    AU - Hermansen, Grith Miriam Maigaard

    AU - Jelsbak, Lars

    PY - 2015

    Y1 - 2015

    N2 - Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have identified a novel gene cluster, which is involved in colistin susceptibility in chronically infecting P. aeruginosa strains. The gene cluster contains two uncharacterized glycosyltransferases and a gene of unknown function. During chronic infection of CF patients one of the glycosyltransferase genes is prone to mutation. Methods: The glycosyltransferase single nucleotide polymorphism (SNP) was reverted to the reference genotype in a clinical isolate and in parallel introduced into the laboratory reference strain PAO1 to provide a clear background for mutational analysis. We evaluated minimal inhibitory concentration by microbroth dilution, virulence in an amoebae model and LPS structure by visualization in a silver-stained gel. Results: Reversion of the SNP to reference genotype resulted in increased colistin susceptibility, reduced virulence in an amoebae model and altered LPS structure. The results indicate that this glycosyltransferase polymorphism is needed for the clinical strain to be fully virulent. However, introducing the SNP into PAO1 did not result in altered phenotypes. These results reveal this uncharacterized glycosyltransferase as a novel in vivo path to colistin resistance by LPS modification. Conclusions: Colistin resistance development in vivo occurs via multiple paths. Here a novel pathway for the development of colistin resistance was described. It involves mutations in a hitherto uncharacterized glycosyltransferase.

    AB - Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have identified a novel gene cluster, which is involved in colistin susceptibility in chronically infecting P. aeruginosa strains. The gene cluster contains two uncharacterized glycosyltransferases and a gene of unknown function. During chronic infection of CF patients one of the glycosyltransferase genes is prone to mutation. Methods: The glycosyltransferase single nucleotide polymorphism (SNP) was reverted to the reference genotype in a clinical isolate and in parallel introduced into the laboratory reference strain PAO1 to provide a clear background for mutational analysis. We evaluated minimal inhibitory concentration by microbroth dilution, virulence in an amoebae model and LPS structure by visualization in a silver-stained gel. Results: Reversion of the SNP to reference genotype resulted in increased colistin susceptibility, reduced virulence in an amoebae model and altered LPS structure. The results indicate that this glycosyltransferase polymorphism is needed for the clinical strain to be fully virulent. However, introducing the SNP into PAO1 did not result in altered phenotypes. These results reveal this uncharacterized glycosyltransferase as a novel in vivo path to colistin resistance by LPS modification. Conclusions: Colistin resistance development in vivo occurs via multiple paths. Here a novel pathway for the development of colistin resistance was described. It involves mutations in a hitherto uncharacterized glycosyltransferase.

    M3 - Conference abstract in proceedings

    SP - 32

    EP - 33

    BT - The Danish Microbiological Society Annual Congress 2015

    CY - Copenhagen

    ER -

    Hermansen GMM, Jelsbak L. Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene. In The Danish Microbiological Society Annual Congress 2015: Programme & Abstracts. Copenhagen. 2015. p. 32-33