Mycobacterium tuberculosis

Talbot, Elizabeth A.; Raffa, Brittany J.

doi:10.1016/b978-0-12-397169-2.00092-5

Cited by 10 publications

(14 citation statements)

References 68 publications

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“…As shown in a range of studies, the simultaneous expression of the cytokines IFN-γ, TNF, and IL-2 enables T cells to a more effective immune response towards different infections in mice and men [60][61][62][63][64]. So-called multifunctional T cells appear to be functionally superior when compared to the single cytokine-producing T cell subsets.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A

et al. 2021

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Interleukin (IL)-17A-producing T helper (Th)17 cells are increasingly being acknowledged to be associated with protective immunity to Mycobacterium tuberculosis (Mtb). Subunit vaccines potently promote protective immune responses against Mtb infection that correlate with an expansion of IL-23-dependent Th17 cells. Previous studies revealed that after vaccination, IL-23 is required for protection against challenge with Mtb but the underlying IL-23-dependent—and possibly IL-17A-mediated—mechanisms remain elusive. Therefore, we here analyzed the early outcome of Mtb infection in C57BL/6, IL-23p19-deficient (−/−), and IL-17A−/− mice after vaccination with the subunit vaccine H1-DDA/TDB to investigate the role of the IL-23-Th17 immune axis for the instruction of vaccine-induced protection. While in IL-23p19−/− mice the protective effect was reduced, protection after vaccination was maintained in IL-17A−/− animals for the course of infection of 6 weeks, indicating that after vaccination with H1-DDA/TDB early protection against Mtb is—although dependent on IL-23—not mediated by IL-17A. In contrast, IL-17A deficiency appears to have an impact on maintaining long-term protection. In fact, IL-23 instructed the vaccine-induced memory immunity in the lung, in particular the sustained expansion of tumor necrosis factor (TNF)+IL-2+ multifunctional T cells, independently of IL-17A. Altogether, a targeted induction of IL-23 during vaccination against Mtb might improve the magnitude and quality of vaccine-induced memory immune responses. Key messages After subunit Mtb vaccination with H1-DDA/TDB, IL-23 but not IL-17A contributes to vaccine-induced early protection against infection with Mtb. IL-17F does not compensate for IL-17A deficiency in terms of H1-DDA/TDB-induced protection against Mtb infection. IL 23 promotes the H1-DDA/TDB-induced accumulation of effector memory T cells independently of IL 17A. IL-23 arbitrates the induction of H1-specific IFN-γ−TNF+IL-2+ double-positive multifunctional CD4 T cells after subunit Mtb vaccination in an IL-17A-independent manner. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A

et al. 2021

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“…Mycobacterium tuberculosis causes a disease called tuberculosis [7][8][9][10]. A recent surge in cases involving strains of this bacterium that is resistant to existing antibiotic treatments demands further search for new drugs to combat the disease [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Complications of other organ systems are also very likely in rare cases of the disease [13]. The first strains of this bacterium were known to affect cattle [14], however, in early 16 th century, it was found that the same bacterium had switched hosts and had begun to affect humans with the same disease [8].…”

Section: Introductionmentioning

confidence: 99%

Construction of Computational 3d Structures of Protein Drug Targets of Mycobacterium Tuberculosis

Rao¹,

Sayeeda²,

Prakash³

et al. 2020

Asian J Pharm Clin Res

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Objective: This study aims in constructing a three-dimensional modeled protein structure of potential drug targets in Mycobacterium tuberculosis bacteria. Methods: The protein models were constructed using SWISS-Model online tool. The constructed protein models were submitted in online database called Protein Model Database (PMDB) for public access to the structures. Results: A total of 100 protein sequences of M. tuberculosis were retrieved from UniProt database and were subjected for sequence similarity search and homology model construction. The constructed models were subjected for Ramachandran plot analysis to validate the quality of the structures. A total of 69 structures were considered to be of significant quality and were submitted to the online database PMDB. Conclusion: These predicted structures would help greatly in identification and drug design to various strains of M. tuberculosis that are sensitive and resistant to different antibiotics. This would greatly help in drug development and personalized drug treatment against different strains of the pathogen. This database would significantly support the structure-based computational drug design applications toward personalized medicine in regard to differences in the various strains of the pathogen.

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“…Tuberculosis is transmitted via droplets from one person to another. The disease most commonly affects the lungs, but it can also involve pleura, lymph nodes, bones and joints, central nervous system, and gastrointestinal tract [ 1 ]. Tuberculous meningitis is highly dangerous for children and people with untreated human immunodeficiency virus infection.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Tuberculostatic Activity Evaluation of Novel Benzazoles with Alkyl, Cycloalkyl or Pyridine Moiety

et al. 2018

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Compounds possessing benzimidazole system exhibit significant antituberculous activity. In order to examine how structure modifications affect tuberculostatic activity, a series of benzazole derivatives were synthesized and screened for their antitubercular activity. The compounds 1–20 were obtained by the reaction between o-diamine, o-aminophenol, or o-aminothiophenol with carboxylic acids or thioamides. The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR spectra, and elemental analysis. Synthesized benzazoles were evaluated for their tuberculostatic activity toward Mycobacterium tuberculosis strains. Quantum chemical calculations were performed to study the molecular geometry and the electronic structure of benzimidazoles GK-151B, 4, 6, and benzoxazole 11, using the Gaussian 03W software (Gaussian, Inc., Wallingford, CT, USA). Three-dimensional structure of benzimidazoles 1–3, MC-9, and GK-151B was determined by ab initio calculation using Gamess-US software. The activity of the received benzimidazoles was moderate or good. All of the benzoxazoles and benzothiazoles demonstrated much lower activity. Benzoxazoles were less active by about 50 times, and benzothiazole by 100 times than the benzimidazole analogs. Quantum chemical calculations showed differences in the distribution of electrostatic potential in the benzazole system of benzimidazoles and benzoxazoles. Three-dimensional structure calculations revealed how the parity of the alkyl substituent at the C2 position impacts the activity. Benzimidazole system is essential for the antituberculosis activity that is associated with the presence of the imine nitrogen atom in N-1 position. Its replacement by an oxygen or sulfur atom results in a decrease of the activity. The parity of the alkyl substituent at the C-2 position also modifies the activity.

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Mycobacterium tuberculosis

Cited by 10 publications

References 68 publications

Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A

Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A

Construction of Computational 3d Structures of Protein Drug Targets of Mycobacterium Tuberculosis

Synthesis and Tuberculostatic Activity Evaluation of Novel Benzazoles with Alkyl, Cycloalkyl or Pyridine Moiety

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