Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model
Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory dis...
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| Format: | Article |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/90981 https://orcid.org/0000-0002-2358-0330 |
| _version_ | 1826201757845291008 |
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| author | Fodah, Ramy A. Scott, Jacob B. Yan, Pearlly Pfeffer, Tia L. Bundschuh, Ralf Warawa, Jonathan M. Tam, Hok Hei |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Fodah, Ramy A. Scott, Jacob B. Yan, Pearlly Pfeffer, Tia L. Bundschuh, Ralf Warawa, Jonathan M. Tam, Hok Hei |
| author_sort | Fodah, Ramy A. |
| collection | MIT |
| description | Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD[subscript 50]<100 CFU) while MGH 78578 is relatively avirulent. |
| first_indexed | 2024-09-23T11:56:18Z |
| format | Article |
| id | mit-1721.1/90981 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:56:18Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/909812022-10-01T07:06:00Z Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model Fodah, Ramy A. Scott, Jacob B. Yan, Pearlly Pfeffer, Tia L. Bundschuh, Ralf Warawa, Jonathan M. Tam, Hok Hei Massachusetts Institute of Technology. Department of Chemical Engineering Tam, Hok Hei Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD[subscript 50]<100 CFU) while MGH 78578 is relatively avirulent. University of Louisville 2014-10-20T13:31:02Z 2014-10-20T13:31:02Z 2014-09 2013-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/90981 Fodah, Ramy A., Jacob B. Scott, Hok-Hei Tam, Pearlly Yan, Tia L. Pfeffer, Ralf Bundschuh, and Jonathan M. Warawa. “Correlation of Klebsiella Pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model.” Edited by Jose A. Bengoechea. PLoS ONE 9, no. 9 (September 9, 2014): e107394. https://orcid.org/0000-0002-2358-0330 en_US http://dx.doi.org/10.1371/journal.pone.0107394 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Fodah, Ramy A. Scott, Jacob B. Yan, Pearlly Pfeffer, Tia L. Bundschuh, Ralf Warawa, Jonathan M. Tam, Hok Hei Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title | Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title_full | Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title_fullStr | Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title_full_unstemmed | Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title_short | Correlation of Klebsiella pneumoniae Comparative Genetic Analyses with Virulence Profiles in a Murine Respiratory Disease Model |
| title_sort | correlation of klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model |
| url | http://hdl.handle.net/1721.1/90981 https://orcid.org/0000-0002-2358-0330 |
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