Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition
Abstract Background Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechan...
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BMC
2024-10-01
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| Series: | BMC Microbiology |
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| Online Access: | https://doi.org/10.1186/s12866-024-03508-w |
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| _version_ | 1850180048233955328 |
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| author | Yingyi Guo Jiong Wang Likang Yao Yijing Wang Yan Zhang Chuyue Zhuo Xu Yang Feifeng Li Jiahui Li Baomo Liu Nanhao He Jiakang Chen Shunian Xiao Zhiwei Lin Chao Zhuo |
| author_facet | Yingyi Guo Jiong Wang Likang Yao Yijing Wang Yan Zhang Chuyue Zhuo Xu Yang Feifeng Li Jiahui Li Baomo Liu Nanhao He Jiakang Chen Shunian Xiao Zhiwei Lin Chao Zhuo |
| author_sort | Yingyi Guo |
| collection | DOAJ |
| description | Abstract Background Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp). Results The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI. Conclusions These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process. |
| format | Article |
| id | doaj-art-5be5e7f40caf48bdab93b5c30a5f0380 |
| institution | OA Journals |
| issn | 1471-2180 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj-art-5be5e7f40caf48bdab93b5c30a5f03802025-08-20T02:18:20ZengBMCBMC Microbiology1471-21802024-10-0124111210.1186/s12866-024-03508-wCeftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisitionYingyi Guo0Jiong Wang1Likang Yao2Yijing Wang3Yan Zhang4Chuyue Zhuo5Xu Yang6Feifeng Li7Jiahui Li8Baomo Liu9Nanhao He10Jiakang Chen11Shunian Xiao12Zhiwei Lin13Chao Zhuo14Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityLaboratory of Respiratory DiseaseGuangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityAbstract Background Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp). Results The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI. Conclusions These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process.https://doi.org/10.1186/s12866-024-03508-wCeftazidime-avibactam resistanceKPCHypermucoviscositywzcK. pneumoniae |
| spellingShingle | Yingyi Guo Jiong Wang Likang Yao Yijing Wang Yan Zhang Chuyue Zhuo Xu Yang Feifeng Li Jiahui Li Baomo Liu Nanhao He Jiakang Chen Shunian Xiao Zhiwei Lin Chao Zhuo Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition BMC Microbiology Ceftazidime-avibactam resistance KPC Hypermucoviscosity wzc K. pneumoniae |
| title | Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| title_full | Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| title_fullStr | Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| title_full_unstemmed | Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| title_short | Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| title_sort | ceftazidime avibactam resistance in kpc producing klebsiella pneumoniae accompanied hypermucoviscosity acquisition |
| topic | Ceftazidime-avibactam resistance KPC Hypermucoviscosity wzc K. pneumoniae |
| url | https://doi.org/10.1186/s12866-024-03508-w |
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