Molecular Assessment of Staphylococcus Aureus Strains in STAT3 Hyper-IgE Syndrome Patients

Abstract

Hyper-IgE syndromes (HIES) are a group of inborn errors of immunity (IEI) caused by monogenic defects such as in the gene STAT3 (STAT3-HIES). Patients suffering from HIES show an increased susceptibility to Staphylococcus aureus (S. aureus) including skin abscesses and pulmonary infections. To assess if the underlying immune defect of STAT3-HIES patients influences the resistance patterns, pathogenicity factors or strain types of S. aureus. We characterized eleven S. aureus strains isolated from STAT3-HIES patients (n = 4) by whole genome sequencing (WGS) to determine presence of resistance and virulence genes. Additionally, we used multi-locus sequence typing (MLST) and protein A (spa) typing to classify these isolates. Bacterial isolates collected from this cohort of STAT3-HIES patients were identified as common spa types in Germany. Only one of the isolates was classified as methicillin-resistant S. aureus (MRSA). For one STAT3 patient WGS illustrated that infection and colonization occurred with different S. aureus isolates rather than one particular clone. The identified S. aureus carriage profile on a molecular level suggests that S. aureus strain type in STAT3-HIES patients is determined by local epidemiology rather than the underlying immune defect highlighting the importance of microbiological assessment prior to antibiotic treatment.

Keywords: STAT3 hyper-IgE syndromes (STAT3-HIES); Staphylococcus aureus (S. aureus); immune evasion cluster (IEC); protein A (spa) typing; whole genome sequencing (WGS).

Fig. 1

Minimum spanning trees of S. aureus isolates illustrate their genotypic relationship. Minimum spanning trees were based on up to 1861 cgMLST target genes, pairwise ignoring missing values. Every circle represents one genotype while connecting lines represent the number of different alleles in a pairwise comparison. a S. aureus isolates of different STAT3-HIES patients (P1–P4, using a different color for each patient). A reference sequence of a reference USA300 strain (NC_007793.1) was included as comparison (white). b The skin colonizing isolates of STAT3-HIES patient P3 (blue). c The isolate causing a lymph node abscess in STAT3-HIES patient P1 (P1.2, dark red) in comparison to three other isolates of the same patient. Isolates P1.1 and P1.3 are both isolated from a nose/throat screening swab (light red) but were collected 8 years apart. Isolate P1.4 (pink, perianal screening swab) has been collect at the same time point as P1.3

Fig. 2

UPGMA-tree based on the toxin and virulence gene profile of eleven S. aureus isolates. The tree was drawn to scale with branches given in absolute alleles distance, using a different color for each patient (colors correspond to Fig. 1)