AUTHOR=Rampersadh Kimona , Salie M. Taariq , Engel Kelin C. , Moodley Clinton , Zühlke Liesl J. , Engel Mark E. 

TITLE=Presence of Group A streptococcus frequently assayed virulence genes in invasive disease: a systematic review and meta-analysis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1337861

DOI=10.3389/fcimb.2024.1337861

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>It is currently unclear what the role of Group A streptococcus (GAS) virulence factors (VFs) is in contributing to the invasive potential of GAS. This work investigated the evidence for the association of GAS VFs with invasive disease.</p></sec><sec><title>Methods</title><p>We employed a broad search strategy for studies reporting the presence of GAS VFs in invasive and non-invasive GAS disease. Data were independently extracted by two reviewers, quality assessed, and meta-analyzed using Stata®.</p></sec><sec><title>Results</title><p>A total of 32 studies reported on 45 putative virulence factors [invasive (n = 3,236); non-invasive (n = 5,218)], characterized by polymerase chain reaction (PCR) (n = 30) and whole-genome sequencing (WGS) (n = 2). The risk of bias was rated as low and moderate, in 23 and 9 studies, respectively. Meta-,analyses of high-quality studies (n = 23) revealed a significant association of <italic>speM</italic> [OR, 1.64 (95%CI, 1.06; 2.52)] with invasive infection. Meta-analysis of WGS studies demonstrated a significant association of <italic>hasA</italic> [OR, 1.91 (95%CI, 1.36; 2.67)] and <italic>speG</italic> [OR, 2.83 (95%CI, 1.63; 4.92)] with invasive GAS (iGAS). Meta-analysis of PCR studies indicated a significant association of <italic>speA</italic> [OR, 1.59 (95%CI, 1.10; 2.30)] and <italic>speK</italic> [OR, 2.95 (95%CI, 1.81; 4.80)] with invasive infection. A significant inverse association was observed between <italic>prtf1</italic> [OR, 0.42 (95%CI, 0.20; 0.87)] and invasive infection.</p></sec><sec><title>Conclusion</title><p>This systematic review and genomic meta-analysis provides evidence of a statistically significant association with invasive infection for the <italic>hasA</italic> gene, while <italic>smeZ</italic>, <italic>ssa</italic>, <italic>pnga3</italic>, <italic>sda1</italic>, <italic>sic</italic>, and <italic>NaDase</italic> show statistically significantly inverse associations with invasive infection. <italic>SpeA</italic>, <italic>speK</italic>, and <italic>speG</italic> are associated with GAS virulence; however, it is unclear if they are markers of invasive infection. This work could possibly aid in developing preventative strategies.</p></sec>