The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus
ABSTRACT Necrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; howe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02033-22 |
| _version_ | 1811198132370800640 |
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| author | Yong-An Shi Tzu-Ching Chen Yan-Wen Chen Yen-Shan Liu Yi-Ywan M. Chen Chih-Ho Lai Cheng-Hsun Chiu Chuan Chiang-Ni |
| author_facet | Yong-An Shi Tzu-Ching Chen Yan-Wen Chen Yen-Shan Liu Yi-Ywan M. Chen Chih-Ho Lai Cheng-Hsun Chiu Chuan Chiang-Ni |
| author_sort | Yong-An Shi |
| collection | DOAJ |
| description | ABSTRACT Necrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; however, the typical cutaneous manifestations are not always presented in patients with GAS necrotizing fasciitis, which would lead to miss- or delayed diagnosis. GAS with spontaneous inactivating mutations in the CovR/CovS two-component regulatory system is significantly associated with destructive diseases such as necrotizing fasciitis and toxic shock syndrome; however, no specific marker has been used to identify these invasive clinical isolates. This study evaluated the sensitivity and specificity of using CovR/CovS-controlled phenotypes to identify CovR/CovS-inactivated isolates. Results showed that the increase of hyaluronic acid capsule production and streptolysin O expression were not consistently presented in CovS-inactivated clinical isolates. The repression of SpeB is the phenotype with 100% sensitivity of identifying in CovS-inactivated isolates among 61 clinical isolates. Nonetheless, this phenotype failed to distinguish RopB-inactivated isolates from CovS-inactivated isolates and cannot be utilized to identify CovR-inactivated mutant and RocA (Regulator of Cov)-inactivated isolates. In this study, we identified and verified that PepO, the endopeptidase which regulates SpeB expression through degrading SpeB-inducing quorum-sensing peptide, was a bacterial marker to identify isolates with defects in the CovR/CovS pathway. These results also inform the potential strategy of developing rapid detection methods to identify invasive GAS variants during infection. IMPORTANCE Necrotizing fasciitis is rapidly progressive and life-threatening; if the initial diagnosis is delayed, deep soft tissue infection can progress to massive tissue destruction and toxic shock syndrome. Group A Streptococcus (GAS) with inactivated mutations in the CovR/CovS two-component regulatory system are related to necrotizing fasciitis and toxic shock syndrome; however, no bacterial marker is available to identify these invasive clinical isolates. Inactivation of CovR/CovS resulted in the increased expression of endopeptidase PepO. Our study showed that the upregulation of PepO mediates a decrease in SpeB-inducing peptide (SIP) in the covR mutant, indicating that CovR/CovS modulates SIP-dependent quorum-sensing activity through PepO. Importantly, the sensitivity and specificity of utilizing PepO to identify clinical isolates with defects in the CovR/CovS pathway, including its upstream RocA regulator, were 100%. Our results suggest that identification of invasive GAS by PepO may be a strategy for preventing severe manifestation or poor prognosis after GAS infection. |
| first_indexed | 2024-04-12T01:26:35Z |
| format | Article |
| id | doaj.art-bfd3a0b5140f44b3a6dbb1f790620a48 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-12T01:26:35Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-bfd3a0b5140f44b3a6dbb1f790620a482022-12-22T03:53:39ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.02033-22The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A StreptococcusYong-An Shi0Tzu-Ching Chen1Yan-Wen Chen2Yen-Shan Liu3Yi-Ywan M. Chen4Chih-Ho Lai5Cheng-Hsun Chiu6Chuan Chiang-Ni7Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, TaiwanABSTRACT Necrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; however, the typical cutaneous manifestations are not always presented in patients with GAS necrotizing fasciitis, which would lead to miss- or delayed diagnosis. GAS with spontaneous inactivating mutations in the CovR/CovS two-component regulatory system is significantly associated with destructive diseases such as necrotizing fasciitis and toxic shock syndrome; however, no specific marker has been used to identify these invasive clinical isolates. This study evaluated the sensitivity and specificity of using CovR/CovS-controlled phenotypes to identify CovR/CovS-inactivated isolates. Results showed that the increase of hyaluronic acid capsule production and streptolysin O expression were not consistently presented in CovS-inactivated clinical isolates. The repression of SpeB is the phenotype with 100% sensitivity of identifying in CovS-inactivated isolates among 61 clinical isolates. Nonetheless, this phenotype failed to distinguish RopB-inactivated isolates from CovS-inactivated isolates and cannot be utilized to identify CovR-inactivated mutant and RocA (Regulator of Cov)-inactivated isolates. In this study, we identified and verified that PepO, the endopeptidase which regulates SpeB expression through degrading SpeB-inducing quorum-sensing peptide, was a bacterial marker to identify isolates with defects in the CovR/CovS pathway. These results also inform the potential strategy of developing rapid detection methods to identify invasive GAS variants during infection. IMPORTANCE Necrotizing fasciitis is rapidly progressive and life-threatening; if the initial diagnosis is delayed, deep soft tissue infection can progress to massive tissue destruction and toxic shock syndrome. Group A Streptococcus (GAS) with inactivated mutations in the CovR/CovS two-component regulatory system are related to necrotizing fasciitis and toxic shock syndrome; however, no bacterial marker is available to identify these invasive clinical isolates. Inactivation of CovR/CovS resulted in the increased expression of endopeptidase PepO. Our study showed that the upregulation of PepO mediates a decrease in SpeB-inducing peptide (SIP) in the covR mutant, indicating that CovR/CovS modulates SIP-dependent quorum-sensing activity through PepO. Importantly, the sensitivity and specificity of utilizing PepO to identify clinical isolates with defects in the CovR/CovS pathway, including its upstream RocA regulator, were 100%. Our results suggest that identification of invasive GAS by PepO may be a strategy for preventing severe manifestation or poor prognosis after GAS infection.https://journals.asm.org/doi/10.1128/spectrum.02033-22CovR/CovSPepORocASpeBSIPgroup A Streptococcus |
| spellingShingle | Yong-An Shi Tzu-Ching Chen Yan-Wen Chen Yen-Shan Liu Yi-Ywan M. Chen Chih-Ho Lai Cheng-Hsun Chiu Chuan Chiang-Ni The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus Microbiology Spectrum CovR/CovS PepO RocA SpeB SIP group A Streptococcus |
| title | The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus |
| title_full | The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus |
| title_fullStr | The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus |
| title_full_unstemmed | The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus |
| title_short | The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus |
| title_sort | bacterial markers of identification of invasive covr covs inactivated group a streptococcus |
| topic | CovR/CovS PepO RocA SpeB SIP group A Streptococcus |
| url | https://journals.asm.org/doi/10.1128/spectrum.02033-22 |
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