Abstract
Invasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive S. pyogenes infection (empyema, septic arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were found in a single pleural fluid sample including streptococcal inhibitor of complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human proteins were detected in patient fluids, 177 (38%) of which could be identified as neutrophil proteins, including alpha enolase and lactotransferrin which, together, were found in all 17 samples. Our data suggest that streptococcal proteins are difficult to detect in infected fluid samples. A vast array of human proteins associated with leukocyte activity are, however, present in samples that deserve further evaluation as potential biomarkers of infection.
Highlights
The important human pathogen Streptococcus pyogenes causes a spectrum of disease, from non-invasive throat infections to invasive necrotising fasciitis, pneumonia and septic shock
Quantitative PCR was undertaken as a surrogate of bacterial density and confirmed the presence of S. pyogenes DNA in all samples bar one, F6, where arthritis associated with bacteremia was subsequently thought to have been reactive
The properties of human proteins found in the fluid samples were examined by correspondence analysis, confirming the observed heterogeneity of samples with regard to disease phenotype and protein content (Supplementary Figure S2). In this small but systematic study of samples obtained from the site of S. pyogenes infection, we were able to positively identify 19 different S. pyogenes proteins in a small number of clinical samples
Summary
The important human pathogen Streptococcus pyogenes (group A Streptococcus, GAS) causes a spectrum of disease, from non-invasive throat infections to invasive necrotising fasciitis, pneumonia and septic shock. Point-of-care rapid antigen tests for sore throat, that recognise the carbohydrate group antigen of S. pyogenes, can be adapted for use in iGAS infection[6,7] but far no protein-based targets have been identified. Clinical infections are caused by a range of emm (M) genotypes that differ in regulatory networks and may result in distinctive proteomes during infection. This is apparent during broth culture[8]. Building on this knowledge, we set out to investigate whether S. pyogenes proteins could be detected in iGAS clinical samples submitted for routine culture to the diagnostic laboratory of a large www.nature.com/scientificreports/. Teaching hospital, with the primary aim of identifying potentially novel diagnostic targets; and with a secondary aim of examining the host proteomic response to iGAS infection
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