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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis
Infection and Immunity, Volume 74, No. 5, Year 2006
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Description
Approximately one-third of the human population is latently infected with Mycobacterium tuberculosis, comprising a critical reservoir for disease reactivation. Despite the importance of latency in maintaining M. tuberculosis in the human population, little is known about the mycobacterial factors that regulate persistence and reactivation. Previous in vitro studies have implicated a family of five related M. tuberculosis proteins, called resuscitation promoting factors (Rpfs), in regulating mycobacterial growth. We studied the in vivo role of M. tuberculosis rpf genes in an established mouse model of M. tuberculosis persistence and reactivation. After an aerosol infection with the M. tuberculosis Erdman wild type (Erdman) or single-deletion rpf mutants to establish chronic infections in mice, reactivation was induced by administration of the nitric oxide (NO) synthase inhibitor aminoguanidine. Of the five rpf deletion mutants tested, one (ΔRv1009) exhibited a delayed reactivation phenotype, manifested by delayed postreactivation growth kinetics and prolonged median survival times among infected animals. Immunophenotypic analysis suggested differences in pulmonary B-cell responses between Erdman- and ΔRv1009-infected mice at advanced stages of reactivation. Analysis of rpf gene expression in the lungs of Erdman-infected mice revealed that relative expression of four of the five rpf-like genes was diminished at late times following reactivation, when bacterial numbers had increased substantially, suggesting that rpf gene expression may be regulated in a growth phase-dependent manner. To our knowledge, ΔRv1009 is the first M. tuberculosis mutant to have a specific defect in reactivation without accompanying growth defects in vitro or during acute infection in vivo. Copyright © 2006, American Society tor Microbiology. All Rights Reserved.
Authors & Co-Authors
Tufariello, Jo Ann M.
United States, New York
Montefiore Medical Center
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Xu, Jiayong
United States, New York
Montefiore Medical Center
Manabe, Yukari C.
United States, Baltimore
Johns Hopkins University
Kesavan, Anup K.
United States, Baltimore
Johns Hopkins University
Jacobs, William Robert
United States, New York
Montefiore Medical Center
United States, Chevy Chase
Howard Hughes Medical Institute
Chan, John
United States, New York
Montefiore Medical Center
Statistics
Citations: 104
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1128/IAI.74.5.2985-2995.2006
ISSN:
00199567
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study