The predictive potential of different molecular markers linked to amikacin susceptibility phenotypes in Pseudomonas aeruginosa

• Published in: PloS one Vol. 17; no. 4; p. e0267396
• Main Authors: Nageeb, Wedad M., Hetta, Helal F.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.04.2022; Public Library of Science (PLoS)
• Subjects: Accuracy; Amikacin; Amikacin - pharmacology; Amikacin - therapeutic use; Aminoglycoside antibiotics; Aminoglycosides; Analysis; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Antimicrobial agents; Biological markers; Biology and Life Sciences; Biomarkers; Complications and side effects; Cystic fibrosis; Diagnostic systems; Drug resistance; Enzymes; Functional analysis; Genes; Genomes; Health aspects; Immunology; Infections; Markers; Medicine and Health Sciences; Microbial Sensitivity Tests; Panels; Patient outcomes; Performance prediction; Phenotype; Phenotypes; Physical Sciences; Prediction models; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Research and Analysis Methods; Susceptibility; Egypt
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0267396

Informed antibiotic prescription offers a practical solution to antibiotic resistance problem. With the increasing affordability of different sequencing technologies, molecular-based resistance prediction would direct proper antibiotic selection and preserve available agents. Amikacin is a broad-spectrum aminoglycoside exhibiting higher clinical efficacy and less resistance rates in Ps . aeruginosa due to its structural nature and its ability to achieve higher serum concentrations at lower therapeutic doses. This study examines the predictive potential of molecular markers underlying amikacin susceptibility phenotypes in order to provide improved diagnostic panels. Using a predictive model, genes and variants underlying amikacin resistance have been statistically and functionally explored in a large comprehensive and diverse set of Ps . aeruginosa completely sequenced genomes. Different genes and variants have been examined for their predictive potential and functional correlation to amikacin susceptibility phenotypes. Three predictive sets of molecular markers have been identified and can be used in a complementary manner, offering promising molecular diagnostics. arm R, nal C, nal D, mex R, mex Z, amp R, rmt D, nal DSer32Asn, fus A1Y552C, fus A1D588G, arn AA170T, and arn DG206C have been identified as the best amikacin resistance predictors in Ps . aeruginosa while fao AT385A, nuo GA890T, nuo GA574T, lpt AT55A, lpt AR62S, pst BR87C, gid BE126G, gid BQ28K, amg SE108Q, and rpl YQ41L have been identified as the best amikacin susceptibility predictors. Combining different measures of predictive performance together with further functional analysis can help design new and more informative molecular diagnostic panels. This would greatly inform and direct point of care diagnosis and prescription, which would consequently preserve amikacin functionality and usefulness.