ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
This article is part of the Research TopicTransmission Dynamics and Population Genomics of Superbug Pathogens of Public Health ImportanceView all 10 articles
The invasive GAS puzzle in Italy: genomic insights from a hospital cohort in a fragmented surveillance landscape
Provisionally accepted
Roberto Rosato1
Giulia Santarelli1
Barbara Fiori1Francesca Romana Monzo1
Giordana Cafaro1Tiziana D'Inzeo1Marilena La Sorda1
Roberta Creti2
Brunella Posteraro1
MAURIZIO SANGUINETTI1
Flavio De Maio1*- 1Agostino Gemelli University Polyclinic (IRCCS), Rome, Italy
- 2Istituto Superiore di Sanita, Rome, Italy
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Streptococcus pyogenes (Group A Streptococcus, GAS) is a re-emerging human pathogen responsible for a wide spectrum of diseases, from mild pharyngitis to life-threatening invasive infections that have risen globally in recent years. We performed a retrospective genomic and epidemiological analysis of 61 invasive Group A Streptococcus (iGAS) isolates collected from 2016 to 2024 at a major tertiary Italian hospital. Whole-genome sequencing, emm typing, phylogenetic reconstruction, and mutational profiling were performed to assess clonal diversity, virulence determinants, antimicrobial resistance (AMR) genes, and mobile genetic elements. Our data revealed high genetic diversity, with multiple emm types identified, including emm1.0, emm28.0, emm89.0, emm22.21, and emm44.0 being the most prevalent. Notably, four isolates belonged to the hypervirulent M1UK sub-lineage, which has circulated in Italy since 2018 without a marked post-pandemic resurgence. Genome-wide analysis identified multiple genomic alterations. Regulatory gene mutations were widespread, particularly in rexB (97%), covS (82%), and rexA (80%) suggesting a complex modulation of virulence pathways. AMR genes were sporadic and largely absent in emm1.0 and M1UK strains, showing 12 or 26 core SNPs, reinforcing the hypothesis that virulence, rather than resistance underpins their clinical relevance. Our findings depict a genetically diverse and evolving S. pyogenes population in Italy, dominated by a few high-risk lineages. The persistence of M1UK strains without explosive spread underscores the influence of local epidemiological contexts and surveillance limitations. This study emphasizes the urgent need for a national genomic surveillance network to enable timely detection of emerging clones and guide public health responses.
Keywords: IgAs, M1UK, Streptococcus pyogenes, Surveillance program, WGS
Received: 12 Aug 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Rosato, Santarelli, Fiori, Monzo, Cafaro, D'Inzeo, La Sorda, Creti, Posteraro, SANGUINETTI and De Maio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Flavio De Maio
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