Production of <it>icaADBC-</it>encoded polysaccharide intercellular adhesin and therapeutic failure in pediatric patients with staphylococcal device-related infections

Abstract Background Biofilm production has been established as a virulence factor which allows Staphylococcus to adhere and persist in medical devices. The objective was to determine whether therapeutic failure in patients infected with Staphylococcus spp. is linked to biofilm production, the presence of the ica operon, and the bacterial insertion sequence element IS256. Methods Staphylococcus spp. isolates from patients with device-related infections were collected. Therapeutic failure with proper antimicrobial treatment was registered. Biofilm phenotype was determined by Congo red test agar and Christensen assay. Presence of the ica operon genes A-D and IS256 was detected by PCR. Differences were compared through x2. Results 100 isolates from staphylococcal infections episodes were included: 40 sepsis/bacteremia, 32 ependymitis, and 28 peritonitis. 73.77% of CoNS and 79.5% of S. aureus isolates harbored the icaD gene, 29% of all isolates IS256-A+ IS256-D genes, icaA and icaB genes were only found in CoNS (27.8% and 21.3% respectively). Therapeutic failure occurred in 95.4.% of patients with a positive IS256-A+ IS256-D S. epidermidis isolate, RR 5.49 (CI 95% 2.24-13.44 p ≤ 0.0001), and 85.76% in CoNS isolates, RR 2.57 (CI 95% 0.97-6.80, p = 0.05). Although none S. aureus was positive for IS256-A + IS256-D, therapeutic failure was observed in 35.8%. Conclusions The presence of icaA/D genes along with the sequence element IS256 was associated with therapeutic failure in most CoNS infections, even though its absence in S. aureus isolates does not ensure therapeutic success.</p

Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling