Molecular and Clinical Characteristics of Clonal Complex 59 Methicillin-Resistant Staphylococcus aureus Infections in Mainland China

et al. (2013) Molecular and Clinical Characteristics of Clonal Complex 59 Methicillin-Resistant Staphylococcus aureus Infections in Mainland China. PLoS ONE 8(8): e70602. doi:10.1371/journal.pone.0070602 Molecular and Clinical Characteristics of Clonal Complex 59 Methicillin-Resistant Staphylococcus aureus Infections in Mainland China Juan Li 0 Lijuan Wang 0 Margaret Ip 0 Mingjiao Sun 0 Jing Sun 0 Guoying Huang 0 Chuanqing Wang 0 Li Deng 0 Yuejie Zheng 0 Zhou Fu 0 Changcong Li 0 Yunxiao Shang 0 Changan Zhao 0 Sangjie Yu 0 Kaihu Yao 0 Yonghong Yang 0 Xuzhuang Shen 0 Herminia de Lencastre, Rockefeller University, United States of America 0 1 Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , Beijing , P. R. China , 2 Department of Microbiology, The Prince of Wales Hospital, The Chinese University of Hong Kong , Shatin, Hong Kong , 3 Pediatric Hospital of Fudan University , Shanghai , P. R. China , 4 Guangzhou Children's Hospital , Guangzhou , P. R. China , 5 Shenzhen Children's Hospital , Shenzhen , P. R. China , 6 Chongqing Children's Hospital , Chongqing , P. R. China , 7 Affiliated Hospital of Wenzhou Medical College , Wenzhou , P. R. China , 8 Shenyang Shengjing Hospital , Shenyang , P. R. China , 9 Guangzhou Maternal and Child Health Hospital , Guangzhou , P. R. China Detailed molecular analyses of Clonal Complex 59 (CC59) methicillin-resistant Staphylococcus aureus (MRSA) isolates from children in seven major cities across Mainland China were examined. A total of 110 CC59 isolates from invasive and noninvasive diseases were analyzed by multilocus sequence typing (MLST), Staphylococcus cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing and pulsed-field gel electrophoresis (PFGE). Antibiotics susceptibilities, carriage of plasmids and 42 virulence genes and the expression of virulence factors were examined. ST59 (101/110, 91.8%) was the predominant sequence type (ST), while single locus variants (SLVs) belonging to ST338 (8/ 110, 7.3%) and ST375 (1/110, 0.9%) were obtained. Three SCCmec types were found, namely type III (2.7%), type IV (74.5%) and type V (22.7%). Seven spa types including t437, which accounted for 87.3%, were determined. Thirteen PFGE types were obtained. PFGE types A and B were the major types totally accounting for 81.8%. The dominant clone was ST59-t437-IVa (65.5%), followed by ST59-t437-V (14.5%). The positive rate of luks-PV and lukF-PV PVL encoding (pvl) gene was 55.5%. Plasmids were detected in 83.6% (92/110) of the strains. The plasmid size ranging from 23.4 kb to 50 kb was most prevalent which accounted for 83.7% (77/92). A significantly lower expression of hla was found in ST59-t437-IVa compared with ST59t437-V. Among the 110 cases, 61.8% of the patients were less than 1 year old. A total of 90 cases (81.8%) were communityassociated (CA) infections whereas 20 cases (18.2%) were hospital-associated (HA) infections. Out of the 110 patients, 36.4% (40/110) were diagnosed with invasive infectious diseases in which ST59-t437-IVa accounted for 67.5% (27/40). In brief, ST59-t437-IVa was proved as the dominant clone in CC59 MRSA strains. The carriage rate of pvl gene was high. CC59 MRSA could result in CA and HA infections. The majortiy of MRSA infection children were in young age. - Funding: The current study was supported by the National Natural Science Foundation of China and the Research Grants Council of Hong Kong Joint Research Scheme (no. 81061160509) and the National Natural Science Foundation of China (no. 81171648). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important public health problem worldwide. MRSA causes skin and soft tissues infections, pneumonia and fatal invasive diseases, such as sepsis [1], necrotizing pneumonia [2], necrotizing fasciitis [3], osteomyelitis [4] and orbital cellulitis [5]. Since the first detection of MRSA, different clonal complexes (CCs) have emerged and become the predominant clones in different geographical regions. A majority of hospital-associated (HA)-MRSA strains belong to five clonal complexes, namely CC5, CC8, CC22, CC30 and CC45. In particular, CC5 (ST5), CC8 (ST239) and CC22 (ST22) are distributed globally [6]. CC30 (ST36) is the major clone in the United States and the United Kingdom. Clone type CC45 (ST45) dominates in the United States and the European countries [7]. In Asia, studies have shown that CC5, CC8 and CC22 are the most prevalent clones whilst CC5, CC8 and CC30 are the major clones in Latin America [8]. Community-associated (CA)-MRSA prevalent clones are more diverse compared with HA-MRSA. For instance, CC8 (ST8) is commonly found in the United States and Canada [911]. CC80 (ST80) is the predominant clone in Europe [12]. ST30 is prevalent in Latin America. In AsiaPacific areas, CC59 has become the dominant clone while ST5 and ST30 are also prevalent [13]. It is reported that ST59 strains and other CC59 isolates have appeared in other countries, such as Hungary, Denmark, United Kingdom [14], Germany [15] and the United States [16]. A multicenter study of European countries confirmed that the most prevalent MRSA clonal type in Finland, Sweden and Poland is related to the Taiwan clone (ST59-IVa, ST59-V) [17]. CC59 strains from Western Australia have been studied in detail and been differentiated into further subtypes [18]. However, limited studies have emphasized the molecular characteristics of CC59 strains and the clinical traits in large sets of samples. Our previous study showed that the predominant clone in Chinese pediatric community acquired infections was ST59-t437-IVa [8,19,20]. The distribution of virulence gene profiles and the presence of exfoliative toxin genes in CA-MRSA have also been determined [21]. In this study, the molecular characteristics of CC59 strains from children in mainland China were described in detail. The expression of virulence factors, the carriage of plasmids and the clinical spectrum of CC59 infections were also elucidated. Materials and Methods Strains Collection A total of 299 MRSA isolates were prospectively collected from June 2005 to December 2011. The collection of MRSA covered eight hospitals namely, Beijing Childrens Hospital, Pediatric Hospital of Fudan University, Guangzhou Childrens Hospital, Shenzhen Childrens Hospital, Chongqing Childrens Hospital, Affiliated Hospital of Wenzhou Medical College, Shenyang Shengjing Hospital and Guangzhou Maternal and Child Health Hospital. The first strain isolated from each patient with informed consent was included in the study. The clini (...truncated)