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      A point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China

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          Abstract

          Adaptation to selective pressures is crucial for clinically important pathogens to establish epidemics, but the underlying evolutionary drivers remain poorly understood. The current epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to public health. In this study we analyzed the genome sequences of 794 CRKP bloodstream isolates collected in 40 hospitals in China between 2014 and 2019. We uncovered a subclonal replacement in the predominant clone ST11, where the previously prevalent subclone OL101:KL47 was replaced by O2v1:KL64 over time in a stepwise manner. O2v1:KL64 carried a higher load of mobile genetic elements, and a point mutation exclusively detected in the recC of O2v1:KL64 significantly promotes recombination proficiency. The epidemic success of O2v1:KL64 was further associated with a hypervirulent sublineage with enhanced resistance to phagocytosis, sulfamethoxazole-trimethoprim, and tetracycline. The phenotypic alterations were linked to the overrepresentation of hypervirulence determinants and antibiotic genes conferred by the acquisition of an rmpA-positive pLVPK-like virulence plasmid and an IncFII-type multidrug-resistant plasmid, respectively. The dissemination of the sublineage was further promoted by more frequent inter-hospital transmission. The results collectively demonstrate that the expansion of O2v1:KL64 is correlated to a repertoire of genomic alterations convergent in a subpopulation with evolutionary advantages.

          Abstract

          Authors carry out a genomic analysis of carbapenem-resistant Klebsiella pneumoniae bloodstream isolates, noting subclonal expansion, associated with the emergence of a hypervirulent subpopulation.

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          Most cited references70

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              Basic local alignment search tool.

              A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.
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                Author and article information

                Contributors
                zhouk@mail.sustech.edu.cn
                xiaoyonghong@zju.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                28 April 2023
                28 April 2023
                2023
                : 14
                : 2464
                Affiliations
                [1 ]GRID grid.263817.9, ISNI 0000 0004 1773 1790, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (Second Clinical Medical College, , Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), ; Shenzhen, 518020 China
                [2 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; Hangzhou, 310003 China
                [3 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Department of Infectious Diseases, Central Clinical School, , Monash University, ; Melbourne, VIC 3004 Australia
                [4 ]GRID grid.440218.b, ISNI 0000 0004 1759 7210, Department of Clinical Laboratory, , Shenzhen People’s Hospital, ; Shenzhen, China
                [5 ]GRID grid.8991.9, ISNI 0000 0004 0425 469X, Department of Infection Biology, Faculty of Infectious and Tropical Diseases, , London School of Hygiene and Tropical Medicine, ; London, WC1E 7HT UK
                [6 ]GRID grid.452661.2, ISNI 0000 0004 1803 6319, The First Affiliated Hospital of Zhejiang University, ; Hangzhou, China
                [7 ]Lishui City Central Hospital, Lishui, China
                [8 ]Affiliated Hospital of Binzhou Medical College, Binzhou, China
                [9 ]GRID grid.460072.7, the First People’s Hospital of Lianyungang, ; Lianyungang, China
                [10 ]GRID grid.412679.f, ISNI 0000 0004 1771 3402, First Affiliated Hospital of Anhui Medical University, ; Hefei, China
                [11 ]GRID grid.452929.1, ISNI 0000 0004 8513 0241, Yijishan Hospital of Wannan Medical College, ; Wuhu, China
                [12 ]GRID grid.411395.b, ISNI 0000 0004 1757 0085, Anhui Provincial Hospital, ; Hefei, China
                [13 ]Wuhan Puren Hospital, Wuhan, China
                [14 ]GRID grid.459509.4, The First People’s Hospital of Jingzhou, ; Jingzhou, China
                [15 ]GRID grid.469519.6, ISNI 0000 0004 1758 070X, People’s Hospital of Ningxia Hui Autonomous Region, ; Yinchuan, China
                [16 ]Anyang District Hospital of Henan Province, Anyang, China
                [17 ]GRID grid.469876.2, ISNI 0000 0004 1798 611X, The Second People’s Hospital of Yunnan Province, ; Kunming, China
                [18 ]GRID grid.417400.6, ISNI 0000 0004 1799 0055, Zhejiang Provincial Hospital of Traditional Chinese Medicine, ; Hangzhou, China
                [19 ]People’s Hospital of Huangshan City, Huangshan, China
                [20 ]Mindong Hospital of Ningde City, Ningde, China
                [21 ]GRID grid.452252.6, ISNI 0000 0004 8342 692X, The Affiliated Hospital of Jining Medical University, ; Jining, China
                [22 ]People’s Hospital of Qingyang, Qingyang, China
                [23 ]Tengzhou Centre People’s Hospital, Tengzhou, China
                [24 ]Lu’an People’s Hospital, Lu′an, China
                [25 ]Xinjiang Uygur Autonomous Region Youyi Hospital, Urumqi, China
                [26 ]People’s Hospital of Yichun City, Yichun, China
                [27 ]GRID grid.460061.5, Jiujiang First People’s Hospital, ; Jiujiang, China
                [28 ]GRID grid.460018.b, ISNI 0000 0004 1769 9639, Shandong Provincial Hospital, ; Jinan, China
                [29 ]GRID grid.490204.b, ISNI 0000 0004 1758 3193, Jingzhou Central Hospital, ; Jingzhou, China
                [30 ]GRID grid.452437.3, the First Affiliated Hospital of Gannan Medical University, ; Ganzhou, China
                [31 ]The First Hospital of Putian City, Putian, China
                [32 ]People’s Hospital of Haining City, Haining, China
                [33 ]GRID grid.461886.5, ISNI 0000 0004 6068 0327, Shengli Oilfield Central Hospital, ; Dongying, China
                [34 ]The Affiliated Hongqi Hospital of Mudanjiang Medicine College, Mudanjiang, China
                [35 ]The Affiliated Hospital of Ningbo Medical School, Ningbo, China
                [36 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Women’s Hospital, Zhejiang University School of Medicine, ; Hangzhou, China
                [37 ]GRID grid.452799.4, The Fourth Affiliated Hospital of Anhui Medical University, ; Hefei, China
                [38 ]Tianchang City People’s Hospital, Chuzhou, China
                [39 ]GRID grid.464423.3, Shanxi Provincial People’s Hospital, ; Taiyuan, China
                [40 ]GRID grid.462987.6, ISNI 0000 0004 1757 7228, The First Affiliated Hospital of Henan University of Science and Technology, ; Luoyang, China
                [41 ]The Second People’s Hospital of Jingzhou, Jingzhou, China
                [42 ]Lu’an Civily Hospital, Lu′an, China
                [43 ]The Second Affiliated Hospital of Bengbu Medicine College, Bengbu, China
                [44 ]GRID grid.256922.8, ISNI 0000 0000 9139 560X, Huaihe Hospital of Henan University, ; Kaifeng, China
                [45 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Qilu Children’s Hospital of Shandong University, ; Jinan, China
                [46 ]Zigong Third People’s Hospital, Zigong, China
                [47 ]GRID grid.452845.a, ISNI 0000 0004 1799 2077, the Second Hospital of Shanxi Medical University, ; Taiyuan, China
                [48 ]the People’s Hospital of Lujiang, Hefei, China
                [49 ]the First People’s Hospital of Jiayuguan, Jiayuguan, China
                [50 ]The Third Hospital of Hefei, Hefei, China
                [51 ]General Hospital of Northern Theater Command, Shenyang, China
                [52 ]Xingang Hospital of Xinyu, Xinyu, China
                [53 ]GRID grid.440218.b, ISNI 0000 0004 1759 7210, Shenzhen People’s Hospital, ; Shenzhen, China
                [54 ]GRID grid.508540.c, ISNI 0000 0004 4914 235X, The First Affiliated Hospital of Xi’an Medical University, ; Xi’an, China
                [55 ]GRID grid.417234.7, ISNI 0000 0004 1808 3203, Gansu Provincial Hospital of Traditional Chinese Medicine, ; Lanzhou, China
                [56 ]GRID grid.459429.7, First People’s Hospital of Chenzhou, ; Chenzhou, China
                [57 ]Changshu Medicine Examination Institute, Changshu, China
                [58 ]Women and Children’s Hospital of Jin’an District, Lu′an, China
                [59 ]Hubin Hospital of Hefei, Hefei, China
                Author information
                http://orcid.org/0000-0003-4553-4527
                http://orcid.org/0000-0002-2913-2133
                http://orcid.org/0000-0003-4677-6747
                http://orcid.org/0009-0002-5417-6709
                http://orcid.org/0000-0002-4033-6639
                http://orcid.org/0009-0001-7311-0644
                http://orcid.org/0000-0002-9212-4048
                http://orcid.org/0000-0002-5843-1386
                Article
                38061
                10.1038/s41467-023-38061-z
                10147710
                37117217
                13aa68f9-0548-4e10-b609-40f8bea170f2
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 December 2022
                : 13 April 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81902030
                Award ID: 81971984
                Award ID: 82172330
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                Uncategorized
                antimicrobial resistance,clinical microbiology,bacterial infection
                Uncategorized
                antimicrobial resistance, clinical microbiology, bacterial infection

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