Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study
ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. MethodsRetrospective cohort study was p...
Gespeichert in:
| Veröffentlicht in: | Frontiers in cellular and infection microbiology 2021-11, Vol.11, p.756782-756782 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 756782 |
|---|---|
| container_issue | |
| container_start_page | 756782 |
| container_title | Frontiers in cellular and infection microbiology |
| container_volume | 11 |
| creator | Hu, Hangbin Zhang, Yan Zhang, Piaopiao Wang, Jie Yuan, Qing Shi, Weixiao Zhang, Sheng Feng, Haiting Chen, Yunbo Yu, Meihong Chen, Hongchao Jiang, Yan Yang, Qing Qu, Tingting |
| description | ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. MethodsRetrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. ResultsAmong the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P |
| doi_str_mv | 10.3389/fcimb.2021.756782 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8592259</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_8529fdc7a6354bacaaf705bc54ad71e1</doaj_id><sourcerecordid>2599075882</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-d6661cf91ce18b0629b8a8da5a4f3c7f7efca11e4e71e7ad59c8c0227d1c1d8b3</originalsourceid><addsrcrecordid>eNpVkk1uFDEQhVsIRKKQA7DzkgUztN0_tlkghRGQEUFESRBLq9qunnHUbTe2O9LsuAPn4TKcBE8mQsSbsvyevrKqXlG8pOWyqoR802s7dktWMrrkTcsFe1IcM1Y1CyaFePrf_ag4jfG2zIeXTMjqeXFU1VyWjZDHxe_3g_cmpoAwkrXrUSfrXSQrmCMa0u3I5wG7aHEYgEwO59E7C5j10MGEDkeI-Ofnr8vgzayt25DLJQEM88Y6H4Fc448ZnUZys5uQ1G31mpzF6LWFlPHfbdqSc7vZki8-JBhs2pGrrERiHVltrYO35IxcYQo-Tvuv3eXOfpu95DrNZveieNbDEPH0oZ4U3z5-uFmdLy6-flqvzi4Wuq5ZWpi2banuJdVIRVe2THYChIEG6r7SvOfYa6AUa-QUOZhGaqFLxrihmhrRVSfF-sA1Hm7VFOwIYac8WHX_4MNGQUhWD6hEw2RvNIe2auoONEDPy6bTTQ0m02lmvTuwprkb0Wh0KcDwCPpYcXarNv4ukyVjjcyAVw-A4PNwY1KjjXq_IId-jip7ZMkbIVi20oNV5wHGgP2_NrRU-xSp-xSpfYrUIUXVXyhkwHY</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2599075882</pqid></control><display><type>article</type><title>Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study</title><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Hu, Hangbin ; Zhang, Yan ; Zhang, Piaopiao ; Wang, Jie ; Yuan, Qing ; Shi, Weixiao ; Zhang, Sheng ; Feng, Haiting ; Chen, Yunbo ; Yu, Meihong ; Chen, Hongchao ; Jiang, Yan ; Yang, Qing ; Qu, Tingting</creator><creatorcontrib>Hu, Hangbin ; Zhang, Yan ; Zhang, Piaopiao ; Wang, Jie ; Yuan, Qing ; Shi, Weixiao ; Zhang, Sheng ; Feng, Haiting ; Chen, Yunbo ; Yu, Meihong ; Chen, Hongchao ; Jiang, Yan ; Yang, Qing ; Qu, Tingting</creatorcontrib><description>ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. MethodsRetrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. ResultsAmong the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the bla KPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-bla KPC-2-ISKpn6-IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. ConclusionsIn the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the bla KPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.</description><identifier>ISSN: 2235-2988</identifier><identifier>EISSN: 2235-2988</identifier><identifier>DOI: 10.3389/fcimb.2021.756782</identifier><identifier>PMID: 34790589</identifier><language>eng</language><publisher>Frontiers Media S.A</publisher><subject>bloodstream infections ; carbapenem-resistant Pseudomonas aeruginosa ; Cellular and Infection Microbiology ; hypervirulence ; KPC ; ST463</subject><ispartof>Frontiers in cellular and infection microbiology, 2021-11, Vol.11, p.756782-756782</ispartof><rights>Copyright © 2021 Hu, Zhang, Zhang, Wang, Yuan, Shi, Zhang, Feng, Chen, Yu, Chen, Jiang, Yang and Qu 2021 Hu, Zhang, Zhang, Wang, Yuan, Shi, Zhang, Feng, Chen, Yu, Chen, Jiang, Yang and Qu</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-d6661cf91ce18b0629b8a8da5a4f3c7f7efca11e4e71e7ad59c8c0227d1c1d8b3</citedby><cites>FETCH-LOGICAL-c442t-d6661cf91ce18b0629b8a8da5a4f3c7f7efca11e4e71e7ad59c8c0227d1c1d8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592259/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592259/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Hu, Hangbin</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zhang, Piaopiao</creatorcontrib><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Yuan, Qing</creatorcontrib><creatorcontrib>Shi, Weixiao</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Feng, Haiting</creatorcontrib><creatorcontrib>Chen, Yunbo</creatorcontrib><creatorcontrib>Yu, Meihong</creatorcontrib><creatorcontrib>Chen, Hongchao</creatorcontrib><creatorcontrib>Jiang, Yan</creatorcontrib><creatorcontrib>Yang, Qing</creatorcontrib><creatorcontrib>Qu, Tingting</creatorcontrib><title>Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study</title><title>Frontiers in cellular and infection microbiology</title><description>ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. MethodsRetrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. ResultsAmong the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the bla KPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-bla KPC-2-ISKpn6-IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. ConclusionsIn the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the bla KPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.</description><subject>bloodstream infections</subject><subject>carbapenem-resistant Pseudomonas aeruginosa</subject><subject>Cellular and Infection Microbiology</subject><subject>hypervirulence</subject><subject>KPC</subject><subject>ST463</subject><issn>2235-2988</issn><issn>2235-2988</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkk1uFDEQhVsIRKKQA7DzkgUztN0_tlkghRGQEUFESRBLq9qunnHUbTe2O9LsuAPn4TKcBE8mQsSbsvyevrKqXlG8pOWyqoR802s7dktWMrrkTcsFe1IcM1Y1CyaFePrf_ag4jfG2zIeXTMjqeXFU1VyWjZDHxe_3g_cmpoAwkrXrUSfrXSQrmCMa0u3I5wG7aHEYgEwO59E7C5j10MGEDkeI-Ofnr8vgzayt25DLJQEM88Y6H4Fc448ZnUZys5uQ1G31mpzF6LWFlPHfbdqSc7vZki8-JBhs2pGrrERiHVltrYO35IxcYQo-Tvuv3eXOfpu95DrNZveieNbDEPH0oZ4U3z5-uFmdLy6-flqvzi4Wuq5ZWpi2banuJdVIRVe2THYChIEG6r7SvOfYa6AUa-QUOZhGaqFLxrihmhrRVSfF-sA1Hm7VFOwIYac8WHX_4MNGQUhWD6hEw2RvNIe2auoONEDPy6bTTQ0m02lmvTuwprkb0Wh0KcDwCPpYcXarNv4ukyVjjcyAVw-A4PNwY1KjjXq_IId-jip7ZMkbIVi20oNV5wHGgP2_NrRU-xSp-xSpfYrUIUXVXyhkwHY</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Hu, Hangbin</creator><creator>Zhang, Yan</creator><creator>Zhang, Piaopiao</creator><creator>Wang, Jie</creator><creator>Yuan, Qing</creator><creator>Shi, Weixiao</creator><creator>Zhang, Sheng</creator><creator>Feng, Haiting</creator><creator>Chen, Yunbo</creator><creator>Yu, Meihong</creator><creator>Chen, Hongchao</creator><creator>Jiang, Yan</creator><creator>Yang, Qing</creator><creator>Qu, Tingting</creator><general>Frontiers Media S.A</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20211101</creationdate><title>Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study</title><author>Hu, Hangbin ; Zhang, Yan ; Zhang, Piaopiao ; Wang, Jie ; Yuan, Qing ; Shi, Weixiao ; Zhang, Sheng ; Feng, Haiting ; Chen, Yunbo ; Yu, Meihong ; Chen, Hongchao ; Jiang, Yan ; Yang, Qing ; Qu, Tingting</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-d6661cf91ce18b0629b8a8da5a4f3c7f7efca11e4e71e7ad59c8c0227d1c1d8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>bloodstream infections</topic><topic>carbapenem-resistant Pseudomonas aeruginosa</topic><topic>Cellular and Infection Microbiology</topic><topic>hypervirulence</topic><topic>KPC</topic><topic>ST463</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Hangbin</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Zhang, Piaopiao</creatorcontrib><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Yuan, Qing</creatorcontrib><creatorcontrib>Shi, Weixiao</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Feng, Haiting</creatorcontrib><creatorcontrib>Chen, Yunbo</creatorcontrib><creatorcontrib>Yu, Meihong</creatorcontrib><creatorcontrib>Chen, Hongchao</creatorcontrib><creatorcontrib>Jiang, Yan</creatorcontrib><creatorcontrib>Yang, Qing</creatorcontrib><creatorcontrib>Qu, Tingting</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in cellular and infection microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Hangbin</au><au>Zhang, Yan</au><au>Zhang, Piaopiao</au><au>Wang, Jie</au><au>Yuan, Qing</au><au>Shi, Weixiao</au><au>Zhang, Sheng</au><au>Feng, Haiting</au><au>Chen, Yunbo</au><au>Yu, Meihong</au><au>Chen, Hongchao</au><au>Jiang, Yan</au><au>Yang, Qing</au><au>Qu, Tingting</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study</atitle><jtitle>Frontiers in cellular and infection microbiology</jtitle><date>2021-11-01</date><risdate>2021</risdate><volume>11</volume><spage>756782</spage><epage>756782</epage><pages>756782-756782</pages><issn>2235-2988</issn><eissn>2235-2988</eissn><abstract>ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. MethodsRetrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. ResultsAmong the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the bla KPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-bla KPC-2-ISKpn6-IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. ConclusionsIn the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the bla KPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.</abstract><pub>Frontiers Media S.A</pub><pmid>34790589</pmid><doi>10.3389/fcimb.2021.756782</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2235-2988 |
| ispartof | Frontiers in cellular and infection microbiology, 2021-11, Vol.11, p.756782-756782 |
| issn | 2235-2988 2235-2988 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8592259 |
| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | bloodstream infections carbapenem-resistant Pseudomonas aeruginosa Cellular and Infection Microbiology hypervirulence KPC ST463 |
| title | Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T05%3A04%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bloodstream%20Infections%20Caused%20by%20Klebsiella%20pneumoniae%20Carbapenemase%E2%80%93Producing%20P.%20aeruginosa%20Sequence%20Type%20463,%20Associated%20With%20High%20Mortality%20Rates%20in%20China:%20A%20Retrospective%20Cohort%20Study&rft.jtitle=Frontiers%20in%20cellular%20and%20infection%20microbiology&rft.au=Hu,%20Hangbin&rft.date=2021-11-01&rft.volume=11&rft.spage=756782&rft.epage=756782&rft.pages=756782-756782&rft.issn=2235-2988&rft.eissn=2235-2988&rft_id=info:doi/10.3389/fcimb.2021.756782&rft_dat=%3Cproquest_doaj_%3E2599075882%3C/proquest_doaj_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2599075882&rft_id=info:pmid/34790589&rft_doaj_id=oai_doaj_org_article_8529fdc7a6354bacaaf705bc54ad71e1&rfr_iscdi=true |