Genetic determinants of antibiotic resistance in Staphylococcus aureus isolated from patients with chronic lung infection in cystic fibrosis

Objective. To investigate antibiotic resistance of S. aureus isolates from cystic fibrosis (CF) patients with chronic lung infection and to identify its genetic determinants. Materials and Methods. The antibiotic susceptibility of 629 S. aureus isolates from pediatric and adult CF patients was analyzed using the disk diffusion method and E-test in accordance with EUCAST guidelines. All strains were screened by PCR for the presence of the mecA and mecC genes. Six S. aureus strains were investigated using whole-genome sequencing (WGS). Results. Methicillin-resistant S. aureus (MRSA) accounted for 8% and 13% of isolates from children and adults, respectively. High resistance rates were detected for benzylpenicillin (70% in children, 33% in adults), erythromycin (31.2% and 35%), and chloramphenicol (21.1% and 23%). All strains remained susceptible to vancomycin, linezolid, teicoplanin, and quinupristin/dalfopristin. WGS of the six strains classified two as sequence type ST1 (MSSA) and four as ST8 (MRSA). The following resistance determinants were identified: 1. genes for antibiotic-inactivating enzymes and target-modifying proteins: mecA (cefoxitin), blaZ (β-lactams), aac(6’)aph(2”) (aminoglycosides), cat(pC194) (chloramphenicol), erm© (macrolidelincosamide-streptogramin B); 2. mutations in antibiotic target genes: grlA, gyrA, and rpoB, conferring resistance to fluoroquinolones and rifampicin; 3. efflux pump genes: lmrS, norA, mgrA, mepA/R, arlR/ S,tet(K) associated with resistance to fluoroquinolones, tetracycline, macrolides, and other antibiotics, were found in all sequenced strains, which is consistent with literature data. Conclusions. This study identified key genetic determinants of antibiotic resistance characteristic of S. aureus isolated from CF patients. These mechanisms encompass various strategies, including enzymatic degradation of the antibiotic, modification of the bacterial antibiotic target, and reduction of intracellular antibiotic concentration—either through decreased cell wall permeability or active efflux from the cell via bacterial efflux pumps.