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Pathog Dis. 2019 Sep 5. pii: ftz045. doi: 10.1093/femspd/ftz045. [Epub ahead of print]

Transcriptional signatures of Mycobacterium tuberculosis in mouse model of intraocular tuberculosis.

Author information

1
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India.
2
Department of Pathology, New York University Langone Medical Center, New York, NY-10010, United States of America.
3
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India.
4
Department of Pathology, New York University Langone Medical Center, New York, NY-10010, United States of America. Veterans Affairs New York Harbor Healthcare System, NY-10010, United States of America.

Abstract

BACKGROUND:

Studies on human intraocular tuberculosis (IOTB) are extremely challenging. For understanding the pathogenesis of IOTB, it is important to investigate the mycobacterial transcriptional changes in ocular environment.

METHODS:

Mice were challenged intravenously with M. tuberculosis H37Rv and at 45 days post-infection, experimental IOTB was confirmed based on bacteriological and molecular assays. M. tuberculosis transcriptome was analyzed in the infected eyes using microarray technology. The identified M. tuberculosis signature genes were further validated and investigated in human IOTB samples using real-time polymerase chain reaction.

RESULTS:

Following intravenous challenge with M. tuberculosis, 45% (5/12) mice showed bacilli in the eyes with positivity for M. tuberculosis RNA in 100% (12/12), thus confirming the paucibacillary nature of IOTB similar to human IOTB. M. tuberculosis transcriptome in these infected eyes showed significant upregulation of 12 M. tuberculosis genes and five of these transcripts (Rv0962c, Rv0984, Rv2612c, Rv0974c and Rv0971c) were also identified in human clinically confirmed cases of IOTB.

CONCLUSIONS:

Differentially expressed mycobacterial genes identified in an intravenously challenged paucibacillary mouse IOTB model and presence of these transcripts in human IOTB samples highlights the possible role of these genes for survival of M. tuberculosis in the ocular environment thus contributing to pathogenesis of IOTB.

KEYWORDS:

Mycobacterium tuberculosisH37Rv, transcriptome; human vitreous sample; intraocular tuberculosis; microarray; mouse model

PMID:
31504463
DOI:
10.1093/femspd/ftz045

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