4.5 Article

Genomic and phenotypic analyses of multidrug-resistant Acinetobacter baumannii NCCP 16007 isolated from a patient with a urinary tract infection

Journal

VIRULENCE
Volume 12, Issue 1, Pages 150-164

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2020.1867421

Keywords

Acinetobacter baumannii; polymyxin B-resistance; whole-genome analysis; horizontal gene transfer; carbapenem-resistance; antibiotic resistance

Funding

  1. National Research Foundation of Korea [NRF-2019R1A2C1088452]
  2. National Research Foundation of Korea [4120200313708] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The multidrug-resistant Acinetobacter baumannii strain NCCP 16007 shows high resistance to Polymyxin B (PMB) and has acquired resistance through horizontal gene transfer of several antibiotic resistance genes. Despite losing some virulence factors, this strain exhibits high pathogenicity in infection models and has a high adhesion capacity during urinary tract infections.
Polymyxin B (PMB) is increasingly used as a last-line antibiotic; however, the emergence of PMB resistance is a serious threat to global health. Here, a total of 40 Acinetobacter baumannii clinical isolates were collected to screen for PMB-resistant strains. Several clinical isolates including NCCP 16007 were far more resistant to PMB (MIC: 128-256 mu g/ml) than the ATCC 17978 strain (MIC: 2 mu g/ml) and appeared to possess resistance to broad-spectrum antibiotics including meropenem and 12 others. Four highly PMB-resistant strains possessed point mutations in the histidine kinase PmrB, leading to an increased expression of pmrC encoding a phosphoethanolamine transferase. Whole-genome analyses revealed that the NCCP 16007 stain had acquired two additional copies of the pmrC gene with phage integrase and 13 antibiotic resistance genes (ARGs) from other pathogens, including Klebsiella pneumoniae and Pseudomonas aeruginosa. The GC ratios of the ARGs (50-60%) were higher than that of the chromosomal backbone (39.06%), further supporting the horizontal gene transfer of ARGs. Comparative genomics with other multidrug-resistant A. baumannii strains revealed that the NCCP 16007 strain has many additional ARGs and has lost several virulence factors including Csu pili and heme oxygenase but exhibited high pathogenicity in Galleria mellonella-infection models. The observation of condensed biofilm through confocal and scanning electron microscopy suggested that the NCCP 16007 strain may possess high adhesion capacity during urinary tract infection. Therefore, our genomic and phenotypic analyses suggested that the multidrug-resistant A. baumannii NCCP 16007 strain possesses high genome plasticity, natural transformation ability, and pathogenicity.

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