Sastalla Inka, Williams Kelli W, Anderson Erik D, Myles Ian A, Reckhow Jensen D, Espinoza-Moraga Marlene, Freeman Alexandra F, Datta Sandip K
Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Pathogens. 2017 Jun 6;6(2):23. doi: 10.3390/pathogens6020023.
Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with and . It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing . Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the isolates ( = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors.
常染色体显性高免疫球蛋白E综合征(AD-HIES)是一种由信号转导子和转录激活子3(STAT3)功能丧失性突变引起的原发性免疫缺陷病。这种免疫紊乱的临床特征是皮肤和鼻窦肺部感染易感性增加,尤其是感染 和 。最近人们认识到,AD-HIES患者的皮肤微生物群发生了改变,某些革兰氏阴性菌和革兰氏阳性葡萄球菌的比例过高。然而,这些改变尚未在物种和菌株水平上进行特征描述。由于感染受毒力因子菌株特异性表达的影响,关于定植菌株特征的信息可能有助于深入了解宿主-病原体相互作用,并有助于指导治疗和预防的管理策略。本研究的目的是确定AD-HIES的免疫缺陷是否会选择独特的定植 菌株。我们使用多位点序列分型(MLST)、蛋白A(spa)分型以及基于PCR的毒素基因检测,对21例AD-HIES患者皮肤上发现的 分离株( = 13)进行了详细分析。我们发现序列类型的多样性较低,并且存在大量表达耐甲氧西林、杀白细胞素(PVL)以及葡萄球菌肠毒素K和Q(SEK、SEQ)的菌株。我们的结果表明,AD-HIES患者可能经常携带具有关键毒力因子的耐药菌株。