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Bacteremia caused by Corynebacterium amycolatum with a novel mutation in gyrA gene that confers high-level quinolone resistance.

ABSTRACT: Although Corynebacterium amycolatum can cause opportunistic infections, it is commonly considered as contaminant. In this report, we present a case of bacteremia caused by C. amycolatum with a novel mutation in the gyrA gene that confers high-level quinolone resistance to the organism.

SUBMITTER: Yoon S

PROVIDER: S-EPMC3111041 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Bacteremia caused by Corynebacterium amycolatum with a novel mutation in gyrA gene that confers high-level quinolone resistance.

Yoon Seoyoung S Kim Heejung H Lee Yangsoon Y Kim Sinyoung S

The Korean journal of laboratory medicine 20110101 1

Although Corynebacterium amycolatum can cause opportunistic infections, it is commonly considered as contaminant. In this report, we present a case of bacteremia caused by C. amycolatum with a novel mutation in the gyrA gene that confers high-level quinolone resistance to the organism. ...[more]

PMID: 21239871

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Project description:Daptomycin, a last-line-of-defense antibiotic for treating Gram-positive infections, is experiencing clinical failure against important infectious agents, including Corynebacterium striatum The recent transition of daptomycin to generic status is projected to dramatically increase availability, use, and clinical failure. Here we confirm the genetic mechanism of high-level daptomycin resistance (HLDR; MIC = >256 µg/ml) in C. striatum, which evolved within a patient during daptomycin therapy, a phenotype recapitulated in vitro In all 8 independent cases tested, loss-of-function mutations in phosphatidylglycerol synthase (pgsA2) were necessary and sufficient for high-level daptomycin resistance. Through lipidomic and biochemical analysis, we demonstrate that daptomycin's activity is dependent on the membrane phosphatidylglycerol (PG) concentration. Until now, the verification of PG as the in vivo target of daptomycin has proven difficult since tested cell model systems were not viable without membrane PG. C. striatum becomes daptomycin resistant at a high level by removing PG from the membrane and changing the membrane composition to maintain viability. This work demonstrates that loss-of-function mutation in pgsA2 and the loss of membrane PG are necessary and sufficient to produce high-level resistance to daptomycin in C. striatumIMPORTANCE Antimicrobial resistance threatens the efficacy of antimicrobial treatment options, including last-line-of-defense drugs. Understanding how this resistance develops can help direct antimicrobial stewardship efforts and is critical to designing the next generation of antimicrobial therapies. Here we determine how Corynebacterium striatum, a skin commensal and opportunistic pathogen, evolved high-level resistance to a drug of last resort, daptomycin. Through a single mutation, this pathogen was able to remove the daptomycin's target, phosphatidylglycerol (PG), from the membrane and evade daptomycin's bactericidal activity. We found that additional compensatory changes were not necessary to support the removal of PG and replacement with phosphatidylinositol (PI). The ease with which C. striatum evolved high-level resistance is cause for alarm and highlights the importance of screening new antimicrobials against a wide range of clinical pathogens which may harbor unique capacities for resistance evolution.

Dataset Information

Bacteremia caused by Corynebacterium amycolatum with a novel mutation in gyrA gene that confers high-level quinolone resistance.

Publications

Bacteremia caused by Corynebacterium amycolatum with a novel mutation in gyrA gene that confers high-level quinolone resistance.

Similar Datasets

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