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CorrectionsMICROBIOLOGY. For the article ''Identification of eIF2B␥ and eIF2␥ as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach'' by Martin Krüger, Carmela Beger, Qiang-Xin Li, Peter J. Welch, Richard Tritz, Mark Leavitt, Jack R. Barber, and Flossie WongStaal, which appeared in number 15, July 18, 2000, of Proc. Natl. Acad. Sci. USA (97,(8566)(8567)(8568)(8569)(8570)(8571), the authors note the following correction. Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF257077, human eIF2B␥ sequence). MICROBIOLOGY. For the article ''Attenuation of virulence inMycobacterium tuberculosis expressing a constitutively active iron repressor'' by Yukari C. Manabe, Beatrice J. Saviola, Li Sun, John R. Murphy, and William R. Bishai, which appeared in number 22, October 26, 1999, of Proc. Natl. Acad. Sci. USA (96, 12844-12848), the authors note the following correction. In Table 2, the IB-1 accession number should read Rv0757. The IB-2 accession number should read Rv0761c. The IB-4 gene name is rrs, the accession number should read MTB00019, and the description should read: ''A portion of the 16S ribosomal RNA.'' In a phylogenetically related organism, Corynebacterium diphtheriae, iron depletion results in the derepression of virulence genes such as the diphtheria toxin (tox) gene by DtxR (diphtheria toxin repressor). The corynebacterial DtxR has a homologue in M. tuberculosis, IdeR (iron-dependent repressor). In the amino terminal 140 aa that contain the Fe 2ϩ and DNA-binding domains of DtxR, IdeR shares 80% identity with DtxR (6). In 1995, ideR was first described by Doukhan et al. (7) in conjunction with the sigA sigB cluster of genes. Subsequently, the ability of mycobacterial IdeR to bind to the corynebacterial tox operator region in a metal ion-dependent manner was demonstrated by gel-shift assay (8). Mutation of ideR in M. smegmatis resulted in derepressed siderophore production in high iron conditions (9). These findings parallel those described in corynebacterial dtxR and suggest that the homology between these two genes may allow for cross-genus functional complementation.Using a positive genetic selection system to clone dtxR alleles, Sun et al. (10) recently isolated and characterized a series of DtxR mutants created by PCR mutagenesis. One of the mutants that bound to the tox operator (toxO) and constitutively repressed reporter gene expression in an iron-independent manner was characterized and found to have a single amino acid substitution of lysine for glutamic acid at position 175 [DtxR(E175K)]. In merodiploid strains harboring both wild-type dtxR and mutant dtxR(E175K) genes, Sun et al. found the mutant to be dominant over the wild-type allele. We postulated that this dominant corynebacterial mutant may be able to constitutively repress IdeR-regulated genes in M. tuberculosis. To test this hypothesis, we constructed an M. tuberculosis strain expressing the dtxR(E175K) positi...

In this study, we determined the effects of glutathione (GSH)-enhancing agents in restoring the levels of GSH in isolated macrophages from individuals with HIV infection thereby resulting in improved control of Mycobacterium tuberculosis. Our results indicate that treatment with N-acetyl cysteine or a liposomal formulation of glutathione (lGSH) resulted in replenishment of reduced also known as free GSH (rGSH), and correlated with a decrease in the intracellular growth of M. tuberculosis. Finally, we observed differences in the amount of the catalytic subunit of glutamine-cysteine ligase (GCLC), glutathione synthase, and glutathione reductase present in macrophages derived from healthy and HIV-infected individuals. These changes correlated with changes in free radicals as well as rGSH levels. Our results indicate that HIV infection leads to increased production of free radicals and decreased production of GCLC resulting in depletion of rGSH and this may lead, in part, to the loss of innate immune function observed in HIV patients. These findings represent a novel mechanism for control of M. tuberculosis infection, and a possible supplement to current HIV treatments.