Integrative genomic, virulence, and transcriptomic analysis of emergent Streptococcus dysgalactiae subspecies equisimilis (SDSE) emm type stG62647 isolates causing human infections

被引:0
|
作者
Eraso, Jesus M. [1 ,2 ,3 ]
Olsen, Randall J. [1 ,2 ,3 ,4 ]
Long, S. Wesley [1 ,2 ,3 ,4 ]
Gadd, Ryan [1 ,2 ]
Boukthir, Sarrah [5 ,6 ,7 ]
Faili, Ahmad [6 ,8 ,9 ]
Kayal, Samer [5 ,6 ,7 ,9 ]
Musser, James M. [1 ,2 ,3 ,4 ]
机构
[1] Houston Methodist Res Inst, Ctr Infect Dis, Lab Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA
[2] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA
[3] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA
[4] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA
[5] CHU Rennes, Serv Bacteriol Hyg Hosp, Rennes, France
[6] INSERM, CIC 1414, Rennes, France
[7] Univ Rennes 1, Fac Med, Rennes, France
[8] Univ Rennes 1, Fac Pharm, Rennes, France
[9] INSERM 1242, OSS Oncogenesis Stress & Signaling, Rennes, France
来源
MBIO | 2024年
关键词
Streptococcus dysgalactiae; genomics; pathogenesis; emerging clone; BETA-HEMOLYTIC STREPTOCOCCI; GROUP-A; GROUP-C; MOLECULAR CHARACTERIZATION; STREPTOLYSIN-S; PYOGENES; REVEALS; IDENTIFICATION; PREVALENCE; BACTEREMIA;
D O I
10.1128/mbio.02578-24
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Streptococcus dysgalactiae subspecies equisimilis (SDSE) is a Gram-positive bacterial pathogen that infects humans and is closely related to group A streptococcus (GAS). Compared with GAS, far less is known about SDSE pathobiology. Increased rates of invasive SDSE infections have recently been reported in many countries. One SDSE emm type (stG62647) is known to cause severe diseases, including necrotizing soft-tissue infections, endocarditis, and osteoarticular infections. To increase our understanding of the molecular pathogenesis of stG62647 SDSE isolates causing human infections, we sequenced to closure the genomes of 120 stG62647 SDSE isolates. The genomes varied in size from 2.1 to 2.24 Mb pairs. The great majority of stG62647 isolates had IS1548 integrated into the silB gene, thereby inactivating it. Regions of difference, such as mobile genetic elements, were the largest source of genomic diversity. All 120 stG62647 isolates were assayed for virulence using a well-established mouse model of necrotizing myositis. An unexpectedly wide range of virulence was identified (20% to 95%), as assessed by near-mortality data. To explore the molecular mechanisms underlying virulence differences, we analyzed RNAseq transcriptome profiles for 38 stG62647 isolates (comprising the 19 least and most virulent) grown in vitro. Genetic polymorphisms were identified from whole-genome sequence data. Collectively, the results suggest that these SDSE isolates use multiple genetic pathways to alter virulence phenotype. The data also suggest that human genetics and underlying medical conditions contribute to disease severity. Our study integrates genomic, mouse virulence, and RNAseq data to advance our understanding of SDSE pathobiology and its molecular pathogenesis.
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页数:21
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