Alas, S.; Emmanouilides, C.; Bonavida, B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin Cancer Res. 7(3): 709-723, 2001. PMID: 11297268
- The authors prove that interleukin-10 can be inhibited as part of a cancer treatment. This is important because researchers could develop something similar in the case of tuberculosis.
Ågren, D.; Schnell, R.; Oehlmann, W.; Singh, M.; Schneider, G. Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase. J. Biol Chem. 283(46): 31567–74, 2008. doi: 10.1074/jbc.M804877200
- The authors determined that CysM in the cysteine biosynthetic pathway uses O-phosphoserine as a sulfur acceptor instead of O-acetyl-L-serine. This demonstrates that more than one part of this pathway needs to be inhibited for a successful drug therapy.
Andries, K.; Verhasselt, P.; Guillemont, J.; Göhlmann, H.W.H.; Neefs, J.; Winkler, H.; Van Gestel, J.; et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 307(5707): 223–27, 2005. doi: 10.1126/science.1106753
- The authors determined that substitution of latent tuberculosis drugs with a diarylquinoline, R207910, inhibited mycobacterial growth in vitro. This was a high-impact paper at the time, and it even showed that this drug targets the proton pump of ATP synthase in Mycobacterium tuberculosis.
Ayubi, E; Doosti-Irani, A.; Mostafavi, E. Do the tuberculin skin test and the QuantiFERON-TB Gold in-tube test agree in detecting latent tuberculosis among high-risk contacts? A systematic review and meta-analysis. Epidemiol Health. 37, 2015. doi: 10.4178/epih/e2015043
- The authors compare the results of a well-established diagnostic test for tuberculosis with a newer diagnostic test to see if the two are in agreement. The results demonstrate that a more reliable test needs to be developed since the two tests only moderately agree.
Cambou, E.; Drancourt, M. Steps towards the discovery of Mycobacterium tuberculosis by Robert Koch, 1882. Clin Microbiol Infect. 20(3): 196-201, 2014. doi: 10.1111/1469-0691.12555
- An in-depth look at the history of the bacterium that causes tuberculosis, as well as the disease itself. It starts with a look at the disease from hundreds of thousands of years ago, and proceeds to discuss the investigations and experiments performed by microbiologist in order to further study the disease, leading up to Robert Koch’s isolation of M. tuberculosis.
CDC. Basic TB Facts. Available here.
Choi, S.H.; Kim, Y.H.; Hebisch, M.; Sliwinski, C.; Lee, S.; D’Avanzo, C.; Chen, H.; Hooli, B.; Asselin, C.; Muffat, J.; Klee, J.B.; Zhang, C.; Wainger, B.J.; Peitz, M.; Kovacs, D.M.; Woolf, C.J.; Wagner, S.L.; Tanzi, R.E.; Kim, D.Y. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature. 515(7526): 274-278, 2014. doi: 10.1038/nature13800
- The authors developed a live model of a human neural cell in a petri dish in order to mimic the effect of Alzheimer’s disease. This is important because researchers could develop a similar model but with a human granuloma environment, which has been difficult to recreate.
Dutta, N.K.; Illei, P.B.; Jain, S.K.; Karakousis, P.C. Characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice. Am. J. Pathol. 184(7): 2045–55, 2014. doi: 10.1016/j.ajpath.2014.03.008
- The authors developed a new mouse model for granulomas in latent tuberculosis that only requires a few bacilli. They also characterized the progression of latent tuberculosis from dormancy to activity. This model could be used for testing therapeutics and biomarkers.
Dutta, N.K.; Karakousis, P.C. Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms. Microbiol Mol Biol Rev. 78(3): 343–71, 2014. doi: 10.1128/MMBR.00010-14
- This is a great review of recent clinical studies and observations on latent tuberculosis, as well as in vitro and animal experimental models. It ties important research and findings together in a nice way.
Elliott, T.O.J.P.; Owolabi, O.; Donkor, S.; Kampmann, B.; Hill, P.C.; Ottenhoff, T.H.M.; Haks, M.C.; Kaufmann, S.H.E.; Maertzdorf, J.; Sutherland, J.S. Dysregulation of apoptosis is a risk factor for tuberculosis disease progression. J. Infect Dis. 212(9): 1469–79, 2015. doi: 10.1093/infdis/jiv238
- The authors determined that effector T cells of latent tuberculosis patients undergo an increase in apoptosis, which increases the risk for disease progression.
Flynn, J.L.; Chan, J.; Triebold, K.J.; Dalton, D.K.; Stewart, T.A.; Bloom, B.R. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J. Exp Med. 178(6): 2249–54, 1993. PubMed Entry
- The authors directly investigated the importance of gamma-interferon, which is produced by T cells, by using a genetic knockout mouse that no longer contains the only gene encoding gamma-interferon.
Gong, J. H.; Zhang, M.; Modlin, R.L.; Linsley, P.S.; Iyer, D.; Lin, Y.; Barnes, P.F. Interleukin-10 downregulates mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. Infect Immun. 64(3): 913–18, 1996. PubMed Entry
- The authors investigated the the result of an interaction between the production of gamma interferon in latent tuberculosis and interleukin-10 since ineffective immunity of intracellular pathogens is associated with a reduced production of gamma interferon. This paper helps demonstrate how interleukin-10 represses immune response, and the effect of neutralizing interleukin-10 on gamma interferon production in latent tuberculosis.
Guirado, E.; Mbawuike, U.; Keiser, T.L.; Arcos, J.; Azad, A.K.; Wang, S.; Schlesinger, L.S. Characterization of host and microbial determinants in individuals with latent tuberculosis infection using a human granuloma model. MBio. 6(1), 2015. doi: 10.1128/mBio.02537-14
- The authors developed and characterized an in vitro granuloma model derived from human peripheral blood mononuclear cells. They provided the first evidence that supports the granulomas, as well as other factors, are different in latent tuberculosis patients.
Li, Y.J; Petrofsky, M.; Bermudez, L.E. Mycobacterium tuberculosis uptake by recipient host macrophages is influenced by environmental conditions in the granuloma of the infectious individual and is associated with impaired production of interleukin-12 and tumor necrosis factor alpha. Infect Immun. 70(11): 6223–30, 2002. doi: 10.1128/IAI.70.11.6223-6230.2002
- The authors investigated the efficiency of the uptake of mycobacterium tuberculosis (the pathogen of latent tuberculosis) under a variety of different environmental conditions. They determined that the conditions of the environment in which the pathogen resides affects its phenotype and efficiency to be taken in by a macrophage.
Madison, B.M. Application of stains in clinical microbiology. Biotech Histochem. 76(3): 119-125, 2001. doi: 10.1080/bih.126.96.36.199
- This article is a nice overview of the different ways in which bacteria can be stained as a way to diagnose infectious diseases. The methods described in this article include Gram staining, acridine orange staining, acid-fast bacilli staining, and more. This is important because tuberculosis can really only be stained for acid-fast bacilli, so it is important to understand why this is the case.
Martineau, A.R.; Honecker, F.U.; Wilkinson, R.J.; Griffiths, C.J. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol. 103(3-5): 793-798, 2007. doi: 10.1016/j.jsbmb.2006.12.052
- The authors review the history of the use of vitamin D for treating tuberculosis. They look at the mechanism of vitamin D with respect to immune response, and also look at three clinical trials in which it was used to treat tuberculosis in the lungs.
Schoenborn, J.R.; Wilson, C.B. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol. 96: 41-101, 2007. doi: 10.1016/S0065-2776(07)96002-2
- The authors provide a good overview of the role of interferon-gamma in immune response. They also review the signaling pathways and interactions that occur as a result of interferon-gamma activity.
Schnell, R.; Schneider, G. Structural enzymology of sulphur metabolism in Mycobacterium tuberculosis. Biochem Biophys Res Commun. 396(1): 33–38, 2010. doi: 10.1016/j.bbrc.2010.02.118
- The authors explore different aspects of the cysteine biosynthetic pathway in order to help determine where ligands and inhibitors could be used to target important aspects of the pathways as a possible therapy.
Smith, I. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev. 16(3): 463-496, 2003. doi: 10.1128/CMR.16.3.463-496.2003
- This article provides a good summary of the history, host and bacterium interactions and responses, clinical trials and treatments, as well as many other aspects of the tuberculosis disease.
Wu, Y.; Du, Z.; Cai, Y.; Peng, W.; Zheng, G.; Zheng, G.; Wu, L.; Li, K. Effective expansion of forkhead box P3+ regulatory T cells via early secreted antigenic target 6 and antigen 85 complex B from Mycobacterium tuberculosis. Mol Med Rep. 11(4): 3134-42, 2015. doi: 10.3892/mmr.2014.3033
- The authors investigated the effect of Mycobacterium tuberculosis on the expansion of the CD4+ and CD25+ forkhead box of T cells since this could have something to do with the unsuccessful immune response by the patient.
Zumla, A.; Chakaya, J.; Centis, R.; D’Ambrosio, L.; Mwaba, P.; Bates, M.; Kapata, N.; Nyirenda, T.; Chanda, D.; Mfinanga, S.; Hoelscher, M.; Maeurer, M.; Battista Migliori, G. Tuberculosis treatment and management- an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 3(3): 220-234, 2015. doi: 10.1016/S2213-2600(15)00063-6
- A good overview of all treatments in use for different forms of tuberculosis in different risk-level patients. This also provides information of treatments currently in trial, which could go on the market in the near future.