scholarly journals Growth of recombinant Mycobacterium tuberculosis H37Ra in mouse macrophages

1997 ◽  
Vol 109 (1) ◽  
pp. 80-83 ◽  
Author(s):  
V FALCONE ◽  
F COLLINS
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mouse Macrophages

scholarly journals Therapeutic Efficacy of SQ641-NE against Mycobacterium tuberculosis

2013 ◽  
Vol 58 (1) ◽  
pp. 587-589 ◽  
Author(s):  
Boris Nikonenko ◽  
Venkata M. Reddy ◽  
Elena Bogatcheva ◽  
Marina Protopopova ◽  
Leo Einck ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Therapeutic Efficacy ◽  
Content Type ◽  
Mouse Macrophages

ABSTRACTA phospholipid-based nanoemulsion formulation of SQ641 (SQ641-NE) was active against intracellularMycobacterium tuberculosisin J774A.1 mouse macrophages, although SQ641 by itself was not. Intravenous (i.v.) SQ641-NE was cleared from circulation and reached peak concentrations in lung and spleen in 1 h. In a murine tuberculosis (TB) model, 8 i.v. doses of SQ641-NE at 100 mg/kg of body weight over 4 weeks caused a 1.73 log10CFU reduction ofM. tuberculosisin spleen and were generally bacteriostatic in lungs.

Mycobacterial 3-hydroxyacyl-l-thioester dehydratase Y derived from Mycobacterium tuberculosis induces COX-2 expression in mouse macrophages through MAPK-NF-κB pathway

2014 ◽  
Vol 161 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Jun-Wei Zhao ◽  
Zhan-Qiang Sun ◽  
Xiang-Yan Zhang ◽  
Yue Zhang ◽  
Jun Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mouse Macrophages ◽  
Cox 2

scholarly journals Dihydrolipoamide Acyltransferase Is Critical for Mycobacterium tuberculosis Pathogenesis

2006 ◽  
Vol 74 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Shuangping Shi ◽  
Sabine Ehrt
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sodium Nitrite ◽  
Pyruvate Dehydrogenase ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Retarded Growth ◽  
Mouse Macrophages

ABSTRACT Mycobacterium tuberculosis has evolved to persist in host macrophages, where it faces a nutrient-poor environment and is exposed to oxidative and nitrosative stress. To defend itself against oxidative/nitrosative stress, M. tuberculosis expresses an NADH-dependent peroxidase and peroxynitrite reductase that is encoded by ahpC, ahpD, lpd, and dlaT. In addition to its central role in the peroxynitrite reductase complex, dlaT (Rv2215) also encodes the E2 component of pyruvate dehydrogenase. Here we demonstrate that inactivation of dlaT in the chromosome of H37Rv resulted in a mutant (H37RvΔdlaT) that displayed phenotypes associated with DlaT's role in metabolism and in defense against nitrosative stress. The H37RvΔdlaT strain showed retarded growth in vitro and was highly susceptible to killing by acidified sodium nitrite. Mouse macrophages readily killed intracellular H37RvΔdlaT organisms, and in mice dlaT was required for full virulence.

scholarly journals Type I interferon signaling mediates Mycobacterium tuberculosis–induced macrophage death

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Li Zhang ◽  
Xiuju Jiang ◽  
Daniel Pfau ◽  
Yan Ling ◽  
Carl F. Nathan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Paracrine Signaling ◽  
Type I Ifns ◽  
Genome Wide ◽  
Mouse Macrophages ◽  
Definition Of

Macrophages help defend the host against Mycobacterium tuberculosis (Mtb), the major cause of tuberculosis (TB). Once phagocytized, Mtb resists killing by macrophages, replicates inside them, and leads to their death, releasing Mtb that can infect other cells. We found that the death of Mtb-infected mouse macrophages in vitro does not appear to proceed by a currently known pathway. Through genome-wide CRISPR-Cas9 screening, we identified a critical role for autocrine or paracrine signaling by macrophage-derived type I IFNs in the death of Mtb-infected macrophages in vitro, and blockade of type I IFN signaling augmented the effect of rifampin, a first-line TB drug, in Mtb-infected mice. Further definition of the pathway of type I IFN–mediated macrophage death may allow for host-directed therapy of TB that is more selective than systemic blockade of type I IFN signaling.

scholarly journals Role of the DinB Homologs Rv1537 and Rv3056 in Mycobacterium tuberculosis

2010 ◽  
Vol 192 (8) ◽  
pp. 2220-2227 ◽  
Author(s):  
Bavesh D. Kana ◽  
Garth L. Abrahams ◽  
Nackmoon Sung ◽  
Digby F. Warner ◽  
Bhavna G. Gordhan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Alkylating Agents ◽  
Spontaneous Mutation ◽  
Dna Polymerases ◽  
Binding Motif ◽  
Dependent Manner ◽  
Mouse Macrophages ◽  
Y Family

ABSTRACT The environment encountered by Mycobacterium tuberculosis during infection is genotoxic. Most bacteria tolerate DNA damage by engaging specialized DNA polymerases that catalyze translesion synthesis (TLS) across sites of damage. M. tuberculosis possesses two putative members of the DinB class of Y-family DNA polymerases, DinB1 (Rv1537) and DinB2 (Rv3056); however, their role in damage tolerance, mutagenesis, and survival is unknown. Here, both dinB1 and dinB2 are shown to be expressed in vitro in a growth phase-dependent manner, with dinB2 levels 12- to 40-fold higher than those of dinB1. Yeast two-hybrid analyses revealed that DinB1, but not DinB2, interacts with the β-clamp, consistent with its canonical C-terminal β-binding motif. However, knockout of dinB1, dinB2, or both had no effect on the susceptibility of M. tuberculosis to compounds that form N 2-dG adducts and alkylating agents. Similarly, deletion of these genes individually or in combination did not affect the rate of spontaneous mutation to rifampin resistance or the spectrum of resistance-conferring rpoB mutations and had no impact on growth or survival in human or mouse macrophages or in mice. Moreover, neither gene conferred a mutator phenotype when expressed ectopically in Mycobacterium smegmatis. The lack of the effect of altering the complements or expression levels of dinB1 and/or dinB2 under conditions predicted to be phenotypically revealing suggests that the DinB homologs from M. tuberculosis do not behave like their counterparts from other organisms.

scholarly journals Characterization of a Glutathione Metabolic Mutant of Mycobacterium tuberculosis and Its Resistance to Glutathione and Nitrosoglutathione

2006 ◽  
Vol 188 (4) ◽  
pp. 1364-1372 ◽  
Author(s):  
Yaswant K. Dayaram ◽  
Meliza T. Talaue ◽  
Nancy D. Connell ◽  
Vishwanath Venketaraman
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Metabolic Enzyme ◽  
Bacterial Cells ◽  
Wild Type ◽  
Mouse Macrophages ◽  
Carrier Molecule ◽  
Glutamyl Transpeptidase

ABSTRACT Glutathione is a tripeptide and antioxidant, synthesized at high levels by cells during the production of reactive oxygen and nitrogen intermediates. Glutathione also serves as a carrier molecule for nitric oxide in the form of S-nitrosoglutathione. Previous studies from this laboratory have shown that glutathione and S-nitrosoglutathione are directly toxic to mycobacteria. Glutathione is not transported into the cells as a tripeptide. Extracellular glutathione is converted to a dipeptide due to the action of transpeptidase, and the dipeptide is then transported into the bacterial cells. The processing of glutathione and S-nitrosoglutathione is brought about by the action of the enzyme γ-glutamyl transpeptidase. The function of γ-glutamyl transpeptidase is to cleave glutathione and S-nitrosoglutathione to the dipeptide (Cys-Gly), which is then transported into the bacterium by the multicomponent ABC transporter dipeptide permease. We have created a mutant strain of Mycobacterium tuberculosis lacking this metabolic enzyme. We investigated the sensitivity of this strain to glutathione and S-nitrosoglutathione compared to that of the wild-type bacteria. In addition, we examined the role of glutathione and/or S-nitrosoglutathione in controlling the growth of intracellular M. tuberculosis inside mouse macrophages.

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