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The authors have developed a simple and highly efficient system for generating allelic exchanges in both fast- and slow-growing mycobacteria. In this procedure a gene of interest, disrupted by a selectable marker, is cloned into a conditionally replicating (temperature-sensitive) shuttle phasmid to generate a specialized transducing mycobacteriophage. The(More)
The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of(More)
Tuberculosis remains a severe worldwide health threat. A thorough understanding of Mycobacterium tuberculosis pathogenesis will facilitate the development of new treatments for tuberculosis. Numerous bacterial pathogens possess specialized protein secretion systems that are dedicated to the export of virulence factors. Mycobacterium tuberculosis is part of(More)
Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ERalpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ERbeta, demanded that we examine the possible participation of ERbeta in regulation of these behaviors. In dramatic contrast(More)
Mycobacterium tuberculosis possesses five genes with significant homology to the resuscitation-promoting factor (Rpf) of Micrococcus luteus. The M. luteus Rpf is a secreted approximately 16-kDa protein which restores active growth to cultures of M. luteus rendered dormant by prolonged incubation in stationary phase. More recently, the Rpf-like proteins of(More)
Though much is known about the function of T lymphocytes in the adaptive immune response against Mycobacterium tuberculosis, comparably little is understood regarding the corresponding role of B lymphocytes. Indicating B cells as components of lymphoid neogenesis during pulmonary tuberculosis, we have identified ectopic germinal centers (GCs) in the lungs(More)
Mycobacterium tuberculosis is successful as a pathogen because of its ability to persist in an immunocompetent host. This bacterium lives within the macrophage, a cell whose function is the elimination of microbes. Recent advances have improved our understanding of how M. tuberculosis evades two major antimicrobial mechanisms of macrophages: phagolysosome(More)
Nitric oxide (NO) and related reactive nitrogen intermediates (RNI) are effective antimycobacterial agents and signal-transducing molecules. The present study uses microarray analysis to examine the effects of RNI on Mycobacterium tuberculosis gene expression. A common set of 53 genes was regulated by two chemically distinct nitric oxide donors. For a(More)
The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To(More)
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(More)