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Article: Truncated Rv2820c enhances mycobacterial virulence ex vivo and in vivo

TitleTruncated Rv2820c enhances mycobacterial virulence ex vivo and in vivo
Authors
Issue Date2011
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/micpath
Citation
Microbial pathogenesis, 2011, v. 50 n. 6, p. 331-335 How to Cite?
AbstractThree hypervirulent strains of Mycobacterium tuberculosis isolated from patients suffering from tuberculous meningitis were shown to grow more rapidly inside human macrophages in our previous study. In the current investigation, genomic polymorphisms in these hypervirulent strains were examined using microarray-based comparative genomic hybridization. Among the five genomic polymorphisms identified, two are in-frame deletion (Rv0071/4 and Rv0613c/6c), two are frameshift deletion (Rv1758' and Rv2820c'), and one is gene replacement (Mb3159). The five genomic polymorphisms were transformed into Mycobacterium smegmatis strain mc(2)155 and the survivability of recombinants inside the human monocytic cell line THP-1 was measured. Interestingly, only the recombinant possessing the Rv2820c' survived significantly better than the vector control after 6 h of ex vivo infection (P < 0.001, one-way ANOVA). The Rv2820c' was later transformed into Mycobacterium marinum strain M and the recombinant was used to infect zebrafish. The in vivo infection also showed that the zebrafish infected with the recombinant possessing the Rv2820c' died significantly faster than the vector control (P = 0.006, log-rank test). The 3' truncation in the Rv2820c' was caused by the Beijing/W-defining deletion RD207 and is commonly found in the Beijing/W strains. The current study demonstrated that the truncated Rv2820c of Beijing/W strains could enhance mycobacterial virulence ex vivo and in vivo. This enhancement, however, was not observed for the intact Rv2820c of the non-Beijing/W strains. The presence of the 3' truncated portion of Rv2820c may interfere with overall protein folding and render the Rv2820c of the non-Beijing/W strains non-functional.
Persistent Identifierhttp://hdl.handle.net/10722/157640
ISSN
2015 Impact Factor: 1.888
2015 SCImago Journal Rankings: 0.932
ISI Accession Number ID
Funding AgencyGrant Number
NIH, NIAIDHHSN266200400091C
Funding Information:

We would like to thank Professor Philip Butcher (St. George's Hospital Medical School, London) for technical advice and supply of microarray slides of M. tuberculosis. We would also like to thank the Colorado State University for providing the expression vector pVV16 as part of NIH, NIAID Contract No. HHSN266200400091C, entitled 'Tuberculosis Vaccine Testing and Research Materials'.

References

 

DC FieldValueLanguage
dc.contributor.authorLam, JTen_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorHo, PLen_US
dc.contributor.authorWeng, XHen_US
dc.contributor.authorZhang, WHen_US
dc.contributor.authorChen, Sen_US
dc.contributor.authorYam, WCen_US
dc.date.accessioned2012-08-08T08:51:52Z-
dc.date.available2012-08-08T08:51:52Z-
dc.date.issued2011en_US
dc.identifier.citationMicrobial pathogenesis, 2011, v. 50 n. 6, p. 331-335en_US
dc.identifier.issn0882-4010en_US
dc.identifier.urihttp://hdl.handle.net/10722/157640-
dc.description.abstractThree hypervirulent strains of Mycobacterium tuberculosis isolated from patients suffering from tuberculous meningitis were shown to grow more rapidly inside human macrophages in our previous study. In the current investigation, genomic polymorphisms in these hypervirulent strains were examined using microarray-based comparative genomic hybridization. Among the five genomic polymorphisms identified, two are in-frame deletion (Rv0071/4 and Rv0613c/6c), two are frameshift deletion (Rv1758' and Rv2820c'), and one is gene replacement (Mb3159). The five genomic polymorphisms were transformed into Mycobacterium smegmatis strain mc(2)155 and the survivability of recombinants inside the human monocytic cell line THP-1 was measured. Interestingly, only the recombinant possessing the Rv2820c' survived significantly better than the vector control after 6 h of ex vivo infection (P < 0.001, one-way ANOVA). The Rv2820c' was later transformed into Mycobacterium marinum strain M and the recombinant was used to infect zebrafish. The in vivo infection also showed that the zebrafish infected with the recombinant possessing the Rv2820c' died significantly faster than the vector control (P = 0.006, log-rank test). The 3' truncation in the Rv2820c' was caused by the Beijing/W-defining deletion RD207 and is commonly found in the Beijing/W strains. The current study demonstrated that the truncated Rv2820c of Beijing/W strains could enhance mycobacterial virulence ex vivo and in vivo. This enhancement, however, was not observed for the intact Rv2820c of the non-Beijing/W strains. The presence of the 3' truncated portion of Rv2820c may interfere with overall protein folding and render the Rv2820c of the non-Beijing/W strains non-functional.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/micpathen_US
dc.relation.ispartofMicrobial pathogenesisen_US
dc.subject.meshFish Diseases - microbiologyen_US
dc.subject.meshMacrophages - microbiologyen_US
dc.subject.meshMycobacterium marinum - genetics - metabolism - pathogenicityen_US
dc.subject.meshMycobacterium smegmatis - genetics - metabolism - pathogenicityen_US
dc.subject.meshMycobacterium tuberculosis - genetics - growth and development - isolation and purification - pathogenicityen_US
dc.titleTruncated Rv2820c enhances mycobacterial virulence ex vivo and in vivoen_US
dc.typeArticleen_US
dc.identifier.emailLam, JT: jasonlam@graduate.hku.hken_US
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_US
dc.identifier.emailHo, PL: plho@hkucc.hku.hken_US
dc.identifier.emailYam, WC: wcyam@hkucc.hku.hk-
dc.identifier.authorityYuen, KY=rp00366en_US
dc.identifier.authorityHo, PL=rp00406en_US
dc.identifier.authorityYam, WC=rp00313en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.micpath.2011.02.008en_US
dc.identifier.pmid21362467-
dc.identifier.scopuseid_2-s2.0-80051470599en_US
dc.identifier.hkuros209852-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051470599&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume50en_US
dc.identifier.issue6en_US
dc.identifier.spage331en_US
dc.identifier.epage335en_US
dc.identifier.isiWOS:000290843000009-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYam, WC=7004281720en_US
dc.identifier.scopusauthoridChen, S=49662860700en_US
dc.identifier.scopusauthoridZhang, WH=49664447500en_US
dc.identifier.scopusauthoridWeng, XH=7102593970en_US
dc.identifier.scopusauthoridHo, PL=7402211363en_US
dc.identifier.scopusauthoridYuen, KY=36078079100en_US
dc.identifier.scopusauthoridLam, JT=22941763000en_US
dc.identifier.citeulike8925740-

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