Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome.

Inka Sastalla,Kelli Williams,Sandip Datta,Jensen Reckhow,Alexandra Freeman,Erik Anderson,Ian Myles,Marlene Espinoza-Moraga

doi:10.3390/pathogens6020023

Abstract

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 Candida and Staphylococcus aureus. 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 S. aureus 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 S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 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.

Highlights

Staphylococcus aureus colonizes human mucosa and skin and is a major human pathogen that causes a strikingly broad range of infections, ranging from relatively minor skin abscesses to potentially life-threatening pneumonia, osteomyelitis, endocarditis, necrotizing fasciitis, septicemia, and toxic shock syndrome [1]
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)
All patients had Signal Transducer and Activator of Transcription 3 (STAT3) mutations confirmed by Sanger sequencing

Summary

Introduction

Staphylococcus aureus colonizes human mucosa and skin and is a major human pathogen that causes a strikingly broad range of infections, ranging from relatively minor skin abscesses to potentially life-threatening pneumonia, osteomyelitis, endocarditis, necrotizing fasciitis, septicemia, and toxic shock syndrome [1]. The multitude of virulence factors and immune response modulators expressed by S. aureus contribute to these diverse disease manifestations [2]. The association of certain clonal groups of MRSA, such as USA300 [5], with outbreaks of infection suggests a critical impact of strain-dependent virulence factor expression. S. aureus can infect otherwise healthy individuals, the increased susceptibility of patients with certain primary immunodeficiencies provides insight into the components of a protective immune response. Autosomal dominant hyper IgE syndrome (AD-HIES; known as Job’s Syndrome), caused by dominant-negative, loss-of-function mutations in the Signal Transducer and Activator of Transcription 3 (STAT3) [9,10,11], is characterized by S. aureus susceptibility, which exacerbates eczematoid dermatitis and causes pneumonia and recurrent skin abscesses in these patients. The effects of STAT3 dysfunction on epithelial antimicrobial function, including impaired differentiation of IL-17-secreting CD4+ T (Th17)

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