Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution
Abstract Background Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequent...
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2018-01-01
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Online Access: | http://link.springer.com/article/10.1186/s13073-018-0514-9 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei He Hong-Xiang Zheng Yanan Wang Katherine Y. Le Qian Liu Jun Shang Yingxin Dai Hongwei Meng Xing Wang Tianming Li Qianqian Gao Juanxiu Qin Huiying Lu Michael Otto Min Li |
spellingShingle |
Lei He Hong-Xiang Zheng Yanan Wang Katherine Y. Le Qian Liu Jun Shang Yingxin Dai Hongwei Meng Xing Wang Tianming Li Qianqian Gao Juanxiu Qin Huiying Lu Michael Otto Min Li Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution Genome Medicine Staphylococcus aureus Community-associated MRSA Livestock-associated MRSA ST398 Virulence Methicillin resistance |
author_facet |
Lei He Hong-Xiang Zheng Yanan Wang Katherine Y. Le Qian Liu Jun Shang Yingxin Dai Hongwei Meng Xing Wang Tianming Li Qianqian Gao Juanxiu Qin Huiying Lu Michael Otto Min Li |
author_sort |
Lei He |
title |
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution |
title_short |
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution |
title_full |
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution |
title_fullStr |
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution |
title_full_unstemmed |
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution |
title_sort |
detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant staphylococcus aureus evolution |
publisher |
BMC |
series |
Genome Medicine |
issn |
1756-994X |
publishDate |
2018-01-01 |
description |
Abstract Background Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA. Methods We used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs. Results We report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains. Conclusions Our study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose. |
topic |
Staphylococcus aureus Community-associated MRSA Livestock-associated MRSA ST398 Virulence Methicillin resistance |
url |
http://link.springer.com/article/10.1186/s13073-018-0514-9 |
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doaj-49b8e04c26b84c3abcadab10877e59422020-11-25T01:43:10ZengBMCGenome Medicine1756-994X2018-01-0110111410.1186/s13073-018-0514-9Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolutionLei He0Hong-Xiang Zheng1Yanan Wang2Katherine Y. Le3Qian Liu4Jun Shang5Yingxin Dai6Hongwei Meng7Xing Wang8Tianming Li9Qianqian Gao10Juanxiu Qin11Huiying Lu12Michael Otto13Min Li14Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityMinistry of Education Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan UniversityDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of HealthDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai Institute for Veterinary Drug & Feeds ControlDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of MedicineDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of HealthDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong UniversityAbstract Background Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA. Methods We used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs. Results We report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains. Conclusions Our study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose.http://link.springer.com/article/10.1186/s13073-018-0514-9Staphylococcus aureusCommunity-associated MRSALivestock-associated MRSAST398VirulenceMethicillin resistance |