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Functional and Immunological Studies Revealed a Second Superantigen Toxin in Staphylococcal Enterotoxin C Producing Staphylococcus aureus Strains.

ABSTRACT: Staphylococcus aureus is a human and animal pathogen as well as a commensal bacterium. It can be a causative agent of severe, life-threatening infections with high mortality, e.g., toxic shock syndrome, septic shock, and multi-organ failure. S. aureus strains secrete a number of toxins. Exotoxins/enterotoxins are considered important in the pathogenesis of the above-mentioned conditions. Exotoxins, e.g., superantigen toxins, cause uncontrolled and polyclonal T cell activation and unregulated activation of inflammatory cytokines. Here we show the importance of genomic analysis of infectious strains in order to identify disease-causing exotoxins. Further, we show through functional analysis of superantigenic properties of staphylococcal exotoxins that even very small amounts of a putative superantigenic contaminant can have a significant mitogenic effect. The results show expression and production of two distinct staphylococcal exotoxins, SEC and SEL, in several strains from clinical isolates. Antibodies against both toxins are required to neutralise the superantigenic activity of staphylococcal supernatants and purified staphylococcal toxins.

SUBMITTER: Roetzer A

PROVIDER: S-EPMC9504012 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Functional and Immunological Studies Revealed a Second Superantigen Toxin in Staphylococcal Enterotoxin C Producing Staphylococcus aureus Strains.

Roetzer Andreas A Model Nina N Laube Jakob J Unterhumer Yvonne Y Haller Guenter G Eibl Martha M MM

Toxins 20220829 9

Staphylococcus aureus is a human and animal pathogen as well as a commensal bacterium. It can be a causative agent of severe, life-threatening infections with high mortality, e.g., toxic shock syndrome, septic shock, and multi-organ failure. S. aureus strains secrete a number of toxins. Exotoxins/enterotoxins are considered important in the pathogenesis of the above-mentioned conditions. Exotoxins, e.g., superantigen toxins, cause uncontrolled and polyclonal T cell activation and u ...[more]

PMID: 36136533

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Project description:Staphylococci producing exfoliative toxins are the causative agents of staphylococcal scalded skin syndrome (SSSS). Exfoliative toxin A (ETA) is encoded by eta, which is harbored on a temperate bacteriophage ΦETA. A recent increase in the incidence of SSSS in North America has been observed; yet it is largely unknown whether this is the result of host range expansion of ΦETA or migration and emergence of established lineages. Here, we detail an outbreak investigation of SSSS in a neonatal intensive care unit, for which we applied whole-genome sequencing (WGS) and phylogenetic analysis of Staphylococcus aureus isolates collected from cases and screening of healthcare workers. We identified the causative strain as a methicillin-susceptible S. aureus (MSSA) sequence type 582 (ST582) possessing ΦETA. To then elucidate the global distribution of ΦETA among staphylococci, we used a recently developed tool to query extant bacterial WGS data for biosamples containing eta, which yielded 436 genomes collected between 1994 and 2019 from 32 countries. Applying population genomic analysis, we resolved the global distribution of S. aureus with lysogenized ΦETA and assessed antibiotic resistance determinants as well as the diversity of ΦETA. The population is highly structured with eight dominant sequence clusters (SCs) that generally aligned with S. aureus ST clonal complexes. The most prevalent STs included ST109 (24.3%), ST15 (13.1%), ST121 (10.1%), and ST582 (7.1%). Among strains with available data, there was an even distribution of isolates from carriage and disease. Only the SC containing ST121 had significantly more isolates collected from disease (69%, n = 46) than carriage (31%, n = 21). Further, we identified 10.6% (46/436) of strains as methicillin-resistant S. aureus (MRSA) based on the presence of mecA and the SCCmec element. Assessment of ΦETA diversity based on nucleotide identity revealed 27 phylogroups, and prophage gene content further resolved 62 clusters. ΦETA was relatively stable within lineages, yet prophage variation is geographically structured. This suggests that the reported increase in incidence is associated with migration and expansion of existing lineages, not the movement of ΦETA to new genomic backgrounds. This revised global view reveals that ΦETA is diverse and is widely distributed on multiple genomic backgrounds whose distribution varies geographically.

Project description:PurposeThis study aims to characterize the wild-type staphylococcal enterotoxin A (SEA)-producing Staphylococcus aureus.Materials and methodsWe identified 29 wild-type sea-positive S. aureus isolates from dairy and meat samples, as well as from patients, measured the amount of SEA produced under favorable cultivation conditions using enzyme-linked immunosorbent assay and sea mRNA transcriptional level and investigated the phage type as well as genetic diversity by means of pulsed-field gel electrophoresis and multilocus sequence typing.ResultsAmong 29 sea-positive isolates, 22 were from food sources (including one outbreak case) and seven from clinical patients. Five enterotoxin gene profiles, namely, sea (14 isolates), sea+sec (9 isolates), sea+seb (4 isolates), sea+seb+sec (1 isolate) and sea+seb+sed (1 isolate), were identified. Multilocus sequence typing generated sequence type (ST)1 (13 isolates), ST6 (5 isolates), ST59 (3 isolates), ST239 (3 isolates), ST5 (2 isolates), ST188 (2 isolate) and ST15 (1 isolate). The amount of SEA per 108 colony-forming unit (CFU) after 24 h of incubation was 1.1-33.5 (mean, 8.74; SD, 7.7) ng/108 CFU. The amount of SEA per hour incubation in the log growth phase was 0.1-12.0 (mean, 2.37; SD, 3.06) ng/108 CFU. Overall, 54.2% of SEA was produced in the log growth phase. Both the transcriptional level of sea mRNA and the amount of SEA in the log growth phase correlated well with the amount of SEA after 24 h of cultivation. Four isolates, namely, SA-212, SA-217, SA-340 and SA-341, were categorized to be of high SEA production (877-1,109 ng/mL, 24 h). The total amount of SEA was mainly based on the amount of SEA in 108 CFU, not the relatively fixed bacterial cell counts (21.1-43×108 CFU/mL). Seven isolates from patients all carried the ФMu3A phage, whereas 21 of the 22 isolates from the environmental sources all carried the ФSa3ms phage.ConclusionThe present study exhibits varied SEA production capacity of the wild sea-positive S. aureus strains. An apparent boundary in phage types between strains from the clinical samples and strains from the environment was also identified.

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Functional and Immunological Studies Revealed a Second Superantigen Toxin in Staphylococcal Enterotoxin C Producing Staphylococcus aureus Strains.

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Functional and Immunological Studies Revealed a Second Superantigen Toxin in Staphylococcal Enterotoxin C Producing <i>Staphylococcus aureus</i> Strains.

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