Academic Journal

Aminoglycoside-Modifying Enzymes Are Sufficient to Make Pseudomonas aeruginosa Clinically Resistant to Key Antibiotics

التفاصيل البيبلوغرافية
العنوان: Aminoglycoside-Modifying Enzymes Are Sufficient to Make Pseudomonas aeruginosa Clinically Resistant to Key Antibiotics
المؤلفون: Aswin Thacharodi, Iain L. Lamont
المصدر: Antibiotics; Volume 11; Issue 7; Pages: 884
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2022
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: aminoglycoside-modifying enzymes, aminoglycoside resistance, Pseudomonas aeruginosa, efflux pumps, horizontal gene transfer, tobramycin, amikacin, gentamicin
الوصف: Aminoglycosides are widely used to treat infections of Pseudomonas aeruginosa. Genes encoding aminoglycoside-modifying enzymes (AMEs), acquired by horizontal gene transfer, are commonly associated with aminoglycoside resistance, but their effects have not been quantified. The aim of this research was to determine the extent to which AMEs increase the antibiotic tolerance of P. aeruginosa. Bioinformatics analysis identified AME-encoding genes in 48 out of 619 clinical isolates of P. aeruginosa, with ant(2′)-Ia and aac(6′)-Ib3, which are associated with tobramcyin and gentamicin resistance, being the most common. These genes and aph(3′)-VIa (amikacin resistance) were deleted from antibiotic-resistant strains. Antibiotic minimum inhibitory concentrations (MICs) were reduced by up to 64-fold, making the mutated bacteria antibiotic-sensitive in several cases. Introduction of the same genes into four antibiotic-susceptible P. aeruginosa strains increased the MIC by up to 128-fold, making the bacteria antibiotic-resistant in all cases. The cloned genes also increased the MIC in mutants lacking the MexXY-OprM efflux pump, which is an important contributor to aminoglycoside resistance, demonstrating that AMEs and this efflux pump act independently in determining levels of aminoglycoside tolerance. Quantification of the effects of AMEs on antibiotic susceptibility demonstrates the large effect that these enzymes have on antibiotic resistance.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
Relation: Mechanism and Evolution of Antibiotic Resistance; https://dx.doi.org/10.3390/antibiotics11070884
DOI: 10.3390/antibiotics11070884
الاتاحة: https://doi.org/10.3390/antibiotics11070884
Rights: https://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.6CC468E0
قاعدة البيانات: BASE
الوصف
DOI:10.3390/antibiotics11070884