Impact of mutations in hVISA isolates on decreased susceptibility to vancomycin, through population analyses profile – area under curve (PAP-AUC)

• Published in: Diagnostic microbiology and infectious disease 2019-11, Vol.95 (3), p.114854-114854, Article 114854
• Main Authors: Silveira, A.C.O., Caierão, J., Silva, C.I., Anzai, E.K., McCulloch, J.A., d'Azevedo, P.A., Sincero, T. C.M.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Humans; hVISA; Microbial Sensitivity Tests; Mutation; rpoB; Staphylococcal Infections - microbiology; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Staphylococcus aureus - isolation & purification; Two-component regulatory systems; Vancomycin - pharmacology; Vancomycin Resistance - genetics; VISA
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2019.06.006

We analyzed sequences of graSR, vraSR, walKR and rpoB genes in hVISA from Brazil. Five isolates showed mutations in at least one gene. rpoB H481N and graS T224I were the most frequent mutations, followed by graR D148Q and walK A468T. Our study reinforces the heterogeneity of genetic patterns among hVISA. •Comparative evaluation of the role of mutations in four target genes (graSR, vraSR, walKR and rpoB) and their impact on decreased susceptibility to vancomycin.•The impact on the phenotype expression was evaluated through the population profile analysis tests – area under the curve (before and after induction), induction of resistance, minimal bactericidal concentration, vancomycin tolerance and slow VISA phenotype.•Mutations in walKR and vraSR, alone, did not demonstrate relevance. Although mutations in graSR have shown the greatest impact on decreased susceptibility, the sum of the performance of other genes may also lead to the development of the hVISA phenotype.•Because of the multiplicity of genes involved, it is difficult to establish a single molecular marker as a predictor of resistance. Phenotypic screening tests (MIC, PAP-AUC) are still the best indicators of therapeutic failure and should be taken into account in the clinical decision to maintain or change vancomycin therapy.