Comparison of the genetic profiles of Burkholderia cenocepacia in patients with cystic fibrosis before and during targeted therapy

Abstract

Introduction. Cystic fibrosis is an autosomal recessive genetic disorder caused by mutations in the CFTR gene and characterized by involvement of the exocrine glands. Of particular clinical importance for patients with cystic fibrosis are bacteria Burkholderia cenocepacia, due to their propensity for persistence and the development of chronic lower respiratory tract infection, which remains the leading cause of death in this patient population. The aim of the study was to analyze the presence of genetic determinants associated with the production of pathogenicity factors in B. cenocepacia isolates from respiratory samples of patients with cystic fibrosis before the start of targeted therapy and for 36 months after its start, regardless of the specific type of targeted therapy. Materials and methods. 151 B. cenocepacia isolates from respiratory samples of 12 patients with cystic fibrosis in the Samara Region were studied, while 32 isolates (21.2%) were isolated from patients before the start of targeted therapy, and 119 (78.8%) after its start for 36 months. The genetic profiles of the strains were analyzed for the presence of 13 genes associated with the production of a number of B. cenocepacia pathogenicity factors of different groups: fliC, fliJ, rpoN, shvR, luxR, atsR, rpfF, katA, katB, hppD, mgtC, zmpA, zmpB. At the second stage of the study, the occurrence of combinations of genes grouped by their functions was assessed: genes associated with bacterial motility and adhesion (fliC, fliJ, rpoN, shvR); genes associated with quorum sensing systems and biofilm formation (shvR, luxR, atsR, rpfF); genes encoding virulence factors associated with evasion of the immune response, tissue damage and existence in conditions of micronutrient deficiency (katA, katB, hppD, mgtC, zmpA, zmpB). Results. During targeted therapy, a statistically significant increase in the prevalence of katA genes (associated with protection against peroxide under iron-deficient conditions) and the ability to grow in the presence of carbon sources was observed (p 0.05). The mgtC-fliC gene combination, associated with survival inside macrophages and loss of motility, was found in 25.0% of isolates before targeted therapy and increased to 45.4% of isolates during targeted therapy, with statistically significant differences. Conclusion. Against the background of targeted therapy, there is a tendency to increase the frequency of strains with genes associated with the possibility of survival inside phagocytes and resistance to oxidative stress (katA, katB, mgtC, rpfF, zmpA, zmpB). In isolates obtained against the background of targeted therapy, there was no significant change in the occurrence of regulatory genes for quorum sensing systems and biofilm formation.