Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae
ABSTRACT: Objectives: To investigate the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae, and characterize the underlying molecular mechanisms. Methods: The population analysis profiles (PAPs) method was used to detect colistin heteroresi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716523001704 |
| _version_ | 1827631002295468032 |
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| author | Tao Wang Xiaojun Wang Suming Chen Jie Zhu Zhichen Zhu Fen Qu Liang Chen Hong Du |
| author_facet | Tao Wang Xiaojun Wang Suming Chen Jie Zhu Zhichen Zhu Fen Qu Liang Chen Hong Du |
| author_sort | Tao Wang |
| collection | DOAJ |
| description | ABSTRACT: Objectives: To investigate the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae, and characterize the underlying molecular mechanisms. Methods: The population analysis profiles (PAPs) method was used to detect colistin heteroresistance. The time-killing assay was used to examine the effect of colistin on carbapenem-resistant Klebsiella pneumoniae (CRKP) in vitro. Galleria mellonella larvae infection model was used to test the potential virulence. qRT-PCR assay was conducted to compare the expression levels of efflux pump genes. Next and third-generation sequencing were conducted to analyse the genomic features. Results: Two colistin-heteroresistant isolates were detected from a multi-center carbapenem-resistant Enterobacterales (CRE) surveillance study in China, which exhibited similar survival rates as the K2 hypervirulent reference strain ATCC 43816 in a G. mellonella larvae model. The two isolates belonged to ST11, harbouring the iucABCD, iutA, iroBCD, and rpmA2 hypervirulent genes and pLVPK-like virulence plasmids. Colistin showed a weak effect on the heteroresistant strains in vitro. The efflux pump genes acrA, acrB, tolC, oqxA, and oqxB were upregulated in this subpopulation compared to the parental strains. Conclusions: This study showed the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae. AcrAB-TolC and OqxAB efflux overexpression were involved in mediating colistin heteroresistance. |
| first_indexed | 2024-03-09T14:14:56Z |
| format | Article |
| id | doaj.art-9f4baf5e79554066b7f2813ffc61023f |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-03-09T14:14:56Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-9f4baf5e79554066b7f2813ffc61023f2023-11-29T04:24:30ZengElsevierJournal of Global Antimicrobial Resistance2213-71652023-12-0135237243Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniaeTao Wang0Xiaojun Wang1Suming Chen2Jie Zhu3Zhichen Zhu4Fen Qu5Liang Chen6Hong Du7Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China; Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Clinical Laboratory, Suzhou Wuzhong People's Hospital, Suzhou, Jiangsu, PR ChinaThe Clinical Laboratory, Fifth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR ChinaLaboratory Medicine Center Aviation General Hospital, Beijing, 100012, ChinaHackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New JerseyDepartment of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China; Corresponding author. Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004 PR China.ABSTRACT: Objectives: To investigate the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae, and characterize the underlying molecular mechanisms. Methods: The population analysis profiles (PAPs) method was used to detect colistin heteroresistance. The time-killing assay was used to examine the effect of colistin on carbapenem-resistant Klebsiella pneumoniae (CRKP) in vitro. Galleria mellonella larvae infection model was used to test the potential virulence. qRT-PCR assay was conducted to compare the expression levels of efflux pump genes. Next and third-generation sequencing were conducted to analyse the genomic features. Results: Two colistin-heteroresistant isolates were detected from a multi-center carbapenem-resistant Enterobacterales (CRE) surveillance study in China, which exhibited similar survival rates as the K2 hypervirulent reference strain ATCC 43816 in a G. mellonella larvae model. The two isolates belonged to ST11, harbouring the iucABCD, iutA, iroBCD, and rpmA2 hypervirulent genes and pLVPK-like virulence plasmids. Colistin showed a weak effect on the heteroresistant strains in vitro. The efflux pump genes acrA, acrB, tolC, oqxA, and oqxB were upregulated in this subpopulation compared to the parental strains. Conclusions: This study showed the clinical emergence of colistin-heteroresistant, hypervirulent, and multidrug-resistant Klebsiella pneumoniae. AcrAB-TolC and OqxAB efflux overexpression were involved in mediating colistin heteroresistance.http://www.sciencedirect.com/science/article/pii/S2213716523001704Carbapenem-resistant Klebsiella pneumoniaeHypervirulent Klebsiella pneumoniaeColistinHeteroresistance |
| spellingShingle | Tao Wang Xiaojun Wang Suming Chen Jie Zhu Zhichen Zhu Fen Qu Liang Chen Hong Du Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae Journal of Global Antimicrobial Resistance Carbapenem-resistant Klebsiella pneumoniae Hypervirulent Klebsiella pneumoniae Colistin Heteroresistance |
| title | Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae |
| title_full | Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae |
| title_fullStr | Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae |
| title_full_unstemmed | Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae |
| title_short | Emergence of colistin-heteroresistant and carbapenem-resistant hypervirulent Klebsiella pneumoniae |
| title_sort | emergence of colistin heteroresistant and carbapenem resistant hypervirulent klebsiella pneumoniae |
| topic | Carbapenem-resistant Klebsiella pneumoniae Hypervirulent Klebsiella pneumoniae Colistin Heteroresistance |
| url | http://www.sciencedirect.com/science/article/pii/S2213716523001704 |
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