Genomic analysis of community-associated methicillinresistant Staphylococcus aureus (CA-MRSA) causing infections in children: a Spanish multicentre study

Silvia Garcia-Cobos^1*Natalia Seco Alberca¹Blanca Bravo-Queipo-de-Llano²Veronica Casquero-García¹Eva Ramírez de Arellano¹Cristina Calvo²Guillermo Ruiz-Carrascoso²Iker Falces Romero²Nieves Larrosa Escartín³Belén Viñado-Pérez³Miguel Ángel Martínez-López³Susana Melendo Pérez³Enrique Ruiz De Gopegui⁴Santiago Pérez Vázquez⁴Jaime Carrasco-Colom⁴BELÉN ARACIL¹Maria Perez-Vazquez¹Ana Mendez-Echevarria²Jesús Oteo-Iglesias¹

• ¹National Microbiology Center, Carlos III Health Institute (ISCIII), Madrid, Spain
• ²University Hospital La Paz Research Institute (IdiPAZ), Madrid, Madrid, Spain
• ³Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain
• ⁴Hospital Universitario Son Espases, Palma de Mallorca, Spain

Objectives. Staphylococcus aureus is one of the most frequent human pathogens causing skin and soft tissue infections (SSTIs) among children. In this study, we investigated the molecular traits of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates causing infections in children in Spain.Methods. Antibiotic susceptibility testing and whole-genome sequencing was performed in ninety-eight CA-MRSA isolates (4.2 median age, 52% male). The phylogenetic relationship, antibiotic resistance, virulence and plasmid replicon genes content was investigated.Results. Resistance rates were: erythromycin, 42.9%, which could be explained by the presence of erm(C), mph(C) and msr(A) genes; tobramycin, 27.5%, aac(6')-Ie/aph(2'')-Ia, and aadD1 genes; tetracycline, 25.5%, mainly due to tet(K) genes; levofloxacin and moxifloxacin, 19.4%, mainly due to mutations in gyrA and parC genes; and gentamycin, 15.3%, due to the presence of aac(6')-Ie/aph(2'')-Ia gene. The most prevalent lineage was ST8-IVc and t008. Most isolates were genetically diverse except for three groups of isolates from the same hospital and one group from different hospitals, which had ≤ 5 allele differences by cgMLST analysis or 0-6 core SNPs by core genome SNP-based analysis. Phage-encoded PVL genes were found in 75.5% of the isolates. Other common virulence genes were related to adhesion (capA, capP), lipid degradation (geh) haemolysis (hlb, hld, hlgABC, hly/hla) and tissue destruction (sspAB).Conclusions. We observed a high genetic diversity among CA-MRSA isolates causing community acquired infections in children in Spain, with ST8-IVc as the most prevalent lineage. Nevertheless, genetic relatedness of some isolates from the same and from different hospitals suggests dissemination of CA-MRSA among children by contact.