A clear understanding of the metabolome of Mycobacterium tuberculosis and its target host cell during infection is fundamental for the development of novel diagnostic tools, effective drugs and vaccines required to combat tuberculosis. The surface-located Mycobacterium tuberculosis curli pili (MTP) adhesin forms initial contact with the host cell and is therefore important for the establishment of infection.
The aim of this investigation was to determine the role of MTP in modulating pathogen and host metabolic pathways in A549 epithelial cells infected with MTP proficient and deficient strains of M. tuberculosis.
Uninfected A549 epithelial cells, and those infected with M. tuberculosis V9124 wild-type strain, Δmtp and the mtp-complemented strains, were subjected to metabolite extraction, two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) and bioinformatic analyses. Univariate and multivariate statistical tests were used to identify metabolites that were significantly differentially produced in the WT-infected and ∆mtp-infected A549 epithelial cell models, comparatively.
A total of 46 metabolites occurred in significantly lower relative concentrations in the Δmtp-infected cells, indicating a reduction in nucleic acid synthesis, amino acid metabolism, glutathione metabolism, oxidative stress, lipid metabolism and peptidoglycan, compared to those cells infected with the WT strain.
The absence of MTP was associated with significant changes to the host metabolome, suggesting that this adhesin is an important contributor to the pathogenicity of M. tuberculosis, and supports previous findings of its potential as a suitable drug, vaccine and diagnostic target.
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The datasets generated and/or analysed during the current study are not publicly available due to collaborative purposes and future publications but are available from the corresponding author on reasonable request. KEGG database reported in this study is accessible via [https://www.genome.jp/kegg/].
Abdool Karim, S. S., Churchyard, G. J., Karim, Q. A., & Lawn, S. D. (2009). HIV infection and tuberculosis in South Africa: An urgent need to escalate the public health response. Lancet (London, England), 374(9693), 921–933.
Alberts, B., Johnson, A., Lewis, J., Walter, P., Raff, M., & Roberts, K. (2002). Molecular Biology of the Cell (4th ed.). International Student Edition: Routledge.
Alteri, C. J. (2005). Novel pili of Mycobacterium tuberculosis. PhD thesis. University of Arizona Tucson.
Alteri, C. J., Xicohténcatl-Cortes, J., Hess, S., Caballero-Olín, G., Girón, J. A., & Friedman, R. L. (2007). Mycobacterium tuberculosis produces pili during human infection. Proceedings of the National Academy of Sciences, 104(12), 5145–5150.
Ashokcoomar, S., Reedoy, K. S., Senzani, S., Loots, D. T., Beukes, D., van Reenen, M., et al. (2020). Mycobacterium tuberculosis curli pili (MTP) deficiency is associated with alterations in cell wall biogenesis, fatty acid metabolism and amino acid synthesis. Metabolomics, 16(9), 97.
Avila, M. A., Garcia-Trevijano, E. R., Lu, S. C., Corrales, F. J., & Mato, J. M. (2004). Methylthioadenosine. International Journal of Biochemistry and Cell Biology, 36(11), 2125–2130.
Bardarov, S., Bardarov, S., Pavelka, M. S., Sambandamurthy, V., Larsen, M., Tufariello, J., et al. (2002). Specialized transduction: An efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis. Microbiology (Reading, England), 148(10), 3007–3017.
Barry, C. E., 3rd, Lee, R. E., Mdluli, K., Sampson, A. E., Schroeder, B. G., Slayden, R. A., et al. (1998). Mycolic acids: Structure, biosynthesis and physiological functions. Progress in Lipid Research, 37(2–3), 143–179.
Basavannacharya, C., Robertson, G., Munshi, T., Keep, N. H., & Bhakta, S. (2010). ATP-dependent MurE ligase in Mycobacterium tuberculosis: Biochemical and structural characterisation. Tuberculosis, 90(1), 16–24.
Bermudez, L. E., & Goodman, J. (1996). Mycobacterium tuberculosis invades and replicates within type II alveolar cells. Infection and Immunity, 64(4), 1400–1406.
Bermudez, L. E., Sangari, F. J., Kolonoski, P., Petrofsky, M., & Goodman, J. (2002). The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infection and Immunity, 70(1), 140–146.
Beste, D. J., Nöh, K., Niedenführ, S., Mendum, T. A., Hawkins, N. D., Ward, J. L., et al. (2013). 13C-flux spectral analysis of host-pathogen metabolism reveals a mixed diet for intracellular Mycobacterium tuberculosis. Chemistry and Biology, 20(8), 1012–1021.
Beukes, D., Du Preez, I., & Loots, D. T. (2019). Total metabolome extraction from mycobacterial cells for GC-MS metabolomics analysis. Microbial Metabolomics, 1859, 121–131.
Birkness, K. A., Deslauriers, M., Bartlett, J. H., White, E. H., King, C. H., & Quinn, F. D. (1999). An in vitro tissue culture bilayer model to examine early events in Mycobacterium tuberculosis infection. Infection and Immunity, 67(2), 653–658.
Carroll, J., Draper, L. A., O’Connor, P. M., Coffey, A., Hill, C., Ross, R. P., et al. (2010). Comparison of the activities of the lantibiotics nisin and lacticin 3147 against clinically significant mycobacteria. International Journal of Antimicrobial Agents, 36(2), 132–136.
Castro-Garza, J., King, C. H., Swords, W. E., & Quinn, F. D. (2002). Demonstration of spread by Mycobacterium tuberculosis bacilli in A549 epithelial cell monolayers. FEMS Microbiology Letters, 212(2), 145–149.
CDC (2018). Centers for Disease Control and Prevention, Tuberculosis (TB) Data and Statistics. https://www.cdc.gov/tb/statistics/default.htm. Accessed 05/06 2018.
Chapeton-Montes, J. A., Plaza, D. F., Barrero, C. A., & Patarroyo, M. A. (2008). Quantitative flow cytometric monitoring of invasion of epithelial cells by Mycobacterium tuberculosis. Frontiers in Bioscience, 13, 650–656.
Consaul, S. A., Wright, L. F., Mahapatra, S., Crick, D. C., & Pavelka, M. S., Jr. (2005). An unusual mutation results in the replacement of diaminopimelate with lanthionine in the peptidoglycan of a mutant strain of Mycobacterium smegmatis. Journal of Bacteriology, 187(5), 1612–1620.
Cumming, B. M., Addicott, K. W., Adamson, J. H., & Steyn, A. J. (2018). Mycobacterium tuberculosis induces decelerated bioenergetic metabolism in human macrophages. ELife. https://doi.org/10.7554/eLife.39169.
de Carvalho, L. P., Fischer, S. M., Marrero, J., Nathan, C., Ehrt, S., & Rhee, K. Y. (2010). Metabolomics of Mycobacterium tuberculosis reveals compartmentalized co-catabolism of carbon substrates. Chemistry and Biology, 17(10), 1122–1131.
Dheda, K., Gumbo, T., Gandhi, N. R., Murray, M., Theron, G., Udwadia, Z., et al. (2014). Global control of tuberculosis: From extensively drug-resistant to untreatable tuberculosis. The Lancet. Respiratory Medicine, 2(4), 321–338.
Dobos, K. M., Spotts, E. A., Quinn, F. D., & King, C. H. (2000). Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation. Infection and Immunity, 68(11), 6300–6310.
Donaghy, J. (2010). Lantibiotics as prospective antimycobacterial agents. Bioengineered Bugs, 1(6), 437–439.
Early, J. V., Casey, A., Martinez-Grau, M. A., Gonzalez Valcarcel, I. C., Vieth, M., Ollinger, J., et al. (2016). Oxadiazoles have butyrate-specific conditional activity against Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 60(6), 3608–3616.
Ehling, S., & Reddy, T. M. (2015). Direct analysis of leucine and its metabolites beta-hydroxy-beta-methylbutyric acid, alpha-ketoisocaproic acid, and alpha-hydroxyisocaproic acid in human breast milk by liquid chromatography-mass spectrometry. Journal of Agricultural and Food Chemistry, 63(34), 7567–7573.
Ehrt, S., Schnappinger, D., & Rhee, K. Y. (2018). Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis. Nature Reviews. Microbiology, 16(8), 496–507.
Eoh, H. (2014). Metabolomics: A window into the adaptive physiology of Mycobacterium tuberculosis. Tuberculosis, 94(6), 538–543.
Gandhi, N. R., Moll, A., Sturm, A. W., Pawinski, R., Govender, T., Lalloo, U., et al. (2006). Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet (London, England), 368(9547), 1575–1580.
Garsin, D. A. (2010). Ethanolamine utilization in bacterial pathogens: roles and regulation. Nature Reviews. Microbiology, 8(4), 290–295.
Guder, A., Wiedemann, I., & Sahl, H. G. (2000). Posttranslationally modified bacteriocins–the lantibiotics. Peptide Science, 55(1), 62–73.
Hallen, A., Jamie, J. F., & Cooper, A. J. (2013). Lysine metabolism in mammalian brain: An update on the importance of recent discoveries. Amino Acids, 45(6), 1249–1272.
Hameed, H., Islam, M. M., Chhotaray, C., Wang, C., Liu, Y., Tan, Y., et al. (2018). Molecular targets related drug resistance mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis strains. Frontiers in Cellular and Infection Microbiology, 8, 114.
Inoue, M., Hamada, S., Ooshima, T., Kotani, S., & Kato, K. (1979). Chemical composition of Streptococcus mutans cell walls and their susceptibility to Flavobacterium L-11 enzyme. Microbiology and Immunology, 23(5), 319–328.
Jackowski, S., & Rock, C. (1996). Escherichia coli and Salmonella typhimurium. In F. C. Neidhardt (Ed.), Cellular and Molecular Biology (pp. 687–694). USA: American society of microbiology.
Kanehisa, M., Furumichi, M., Tanabe, M., Sato, Y., & Morishima, K. (2017). KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Research, 45(D1), D353–d361.
Karlsson, E., Shin, J. H., Westman, G., Eriksson, L. A., Olsson, L., & Mapelli, V. (2018). In silico and in vitro studies of the reduction of unsaturated α, β bonds of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid - Important steps towards biobased production of adipic acid. PLoS ONE, 13(2), e0193503–e0193503.
Kato, K., Umemoto, T., Sagawa, H., & Kotani, S. (1979). Lanthionine as an essential constituent of cell wall peptidoglycan of Fusobacterium nucleatum. Current Microbiology, 3(3), 147–151.
Kawamoto, I., Oka, T., & Nara, T. (1981). Cell wall composition of Micromonospora olivoasterospora, Micromonospora sagamiensis, and related organisms. Journal of Bacteriology, 146(2), 527–534.
Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., et al. (2019). PubChem 2019 update: Improved access to chemical data. Nucleic Acids Research, 47(D1), D1102–D1109.
Kinhikar, A. G., Vargas, D., Li, H., Mahaffey, S. B., Hinds, L., Belisle, J. T., et al. (2006). Mycobacterium tuberculosis malate synthase is a laminin-binding adhesin. Molecular microbiology, 60(4), 999–1013.
Kinsella, R. J., Fitzpatrick, D. A., Creevey, C. J., & McInerney, J. O. (2003). Fatty acid biosynthesis in Mycobacterium tuberculosis: Lateral gene transfer, adaptive evolution, and gene duplication. Proceedings of the National Academy of Sciences of the United States of America, 100(18), 10320–10325.
Kline, K. A., Fälker, S., Dahlberg, S., Normark, S., & Henriques-Normark, B. (2009). Bacterial adhesins in host-microbe interactions. Cell Host and Microbe, 5(6), 580–592.
Landaas, S. (1975). Accumulation of 3-hydroxyisobutyric acid, 2-methyl-3-hydroxybutyric acid and 3-hydroxyisovaleric acid in ketoacidosis. Clinica Chimica Acta; International Journal of Clinical Chemistry, 64(2), 143–154.
Larsen, M. H., Biermann, K., Tandberg, S., Hsu, T., & Jacobs Jr, W. R. (2007). Genetic manipulation of Mycobacterium tuberculosis. Current Protocols in Microbiology, 6(1), 10A-2.
Lin, W., Mathys, V., Ang, E. L. Y., Koh, V. H. Q., Martínez Gómez, J. M., Ang, M. L. T., et al. (2012). Urease activity represents an alternative pathway for Mycobacterium tuberculosis nitrogen metabolism. Infection and Immunity, 80(8), 2771–2779.
Lubman, R., Kim, K., & Crandall, E. (1997). Alveolar epithelial barrier properties The Lung: Scientific Foundations. In: Crystal, R. G., West, J. B., Weibel, E. R., Barnes, P. J., (Eds), Lippincott-Raven, Philadelphia
Loots, D. T., Swanepoel, C. C., Newton-Foot, M., & Gey van Pittius, N. C. (2016). A metabolomics investigation of the function of the ESX-1 gene cluster in mycobacteria. Microbial Pathogenesis, 100, 268–275.
Magdaleno, A., Ahn, I.-Y., Paes, L. S., & Silber, A. M. (2009). Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi. PLoS ONE, 4(2), e4534–e4534.
Mahapatra, S., Hess, A. M., Johnson, J. L., Eisenach, K. D., DeGroote, M. A., Gitta, P., et al. (2014). A metabolic biosignature of early response to anti-tuberculosis treatment. BMC Infectious Diseases, 14(1), 53.
Mavi, P. S., Singh, S., & Kumar, A. (2019). Reductive stress: new insights in physiology and drug tolerance of Mycobacterium. Antioxidants and Redox Signaling. https://doi.org/10.1089/ars.2019.7867.
McDonough, K. A., & Kress, Y. (1995). Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis. Infection and Immunity, 63(12), 4802–4811.
Mengin-Lecreulx, D., Blanot, D., & van Heijenoort, J. (1994). Replacement of diaminopimelic acid by cystathionine or lanthionine in the peptidoglycan of Escherichia coli. Journal of Bacteriology, 176(14), 4321–4327.
Menozzi, F. D., Bischoff, R., Fort, E., Brennan, M. J., & Locht, C. (1998). Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin. Proceedings of the National Academy of Sciences of the United States of America, 95(21), 12625–12630.
Mills, G. C., & Mills, J. S. (1985). Urinary excretion of methylthioadenosine in immunodeficient children. Clinica Chimica Acta International Journal of Clinical Chemistry, 147(1), 15–23.
Mobley, C. B., Fox, C. D., Ferguson, B. S., Amin, R. H., Dalbo, V. J., Baier, S., et al. (2014). L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy. Journal of the International Society of Sports Nutrition, 11, 38–38.
Monteville, T. J., Chung, H., Chikindas, M. L., & Chen, Y. (1999). Nisin A depletes intracellular ATP and acts in bactericidal manner against Mycobacterium smegatis. Letters in Applied Microbiology, 28(3), 189–191.
Morris, D., Khurasany, M., Nguyen, T., Kim, J., Guilford, F., Mehta, R., et al. (2013). Glutathione and infection. Biochimica et Biophysica Acta (BBA) - olecular and Cell Biology of Lipids, 1830(5), 3329–3349.
Naidoo, K., Gengiah, S., Yende-Zuma, N., Padayatchi, N., Barker, P., Nunn, A., et al. (2019). Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): A cluster randomized controlled trial protocol. Implementation Science, 12, 129.
Naidoo, N., Ramsugit, S., & Pillay, M. (2014). Mycobacterium tuberculosis pili (mtp), a putative biomarker for a tuberculosis diagnostic test. Tuberculosis, 94(3), 338–345.
Naidoo, N., Pillay, B., Bubb, M., Pym, A., Chiliza, T., Naidoo, K., et al. (2018). Evaluation of a synthetic peptide for the detection of anti-Mycobacterium tuberculosis curli pili IgG antibodies in patients with pulmonary tuberculosis. Tuberculosis (Edinburgh, Scotland), 109, 80–84.
Passalacqua, K. D., Charbonneau, M.-E., & O'Riordan, M. X. D. (2016). Bacterial metabolism shapes the host-pathogen interface. Microbiology Spectrum, 4(3), 15–41.
Pavelka, M. S., Jr., & Jacobs, W. R., Jr. (1999). Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette-Guérin, and Mycobacterium tuberculosis H37Rv by allelic exchange. Journal of bacteriology, 181(16), 4780–4789.
Pethe, K., Aumercier, M., Fort, E., Gatot, C., Locht, C., & Menozzi, F. D. (2000). Characterization of the heparin-binding site of the mycobacterial heparin-binding hemagglutinin adhesin. Journal of Biological Chemistry, 275(19), 14273–14280.
Prasad, D., Arora, D., Nandicoori, V. K., & Muniyappa, K. (2019). Elucidating the functional role of Mycobacterium smegmatis recX in stress response. Sci Rep, 9, 10912.
du Preez, I., & Loots, D. T. (2013). New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa. Tuberculosis (Edinb), 93(3), 330–337.
Ramsugit, S., Guma, S., Pillay, B., Jain, P., Larsen, M. H., Danaviah, S., et al. (2013). Pili contribute to biofilm formation in vitro in Mycobacterium tuberculosis. Antonie van Leeuwenhoek, 104(5), 725–735.
Ramsugit, S., & Pillay, M. (2019). Curli pili affect the intracellular survival of Mycobacterium tuberculosis. The Journal of Infection in Developing Countries, 13(02), 179–180.
Ramsugit, S., Pillay, B., & Pillay, M. (2016). Evaluation of the role of Mycobacterium tuberculosis pili (MTP) as an adhesin, invasin, and cytokine inducer of epithelial cells. The Brazilian Journal of Infectious Diseases, 20(2), 160–165.
Ramsugit, S., & Pillay, M. (2014). Mycobacterium tuberculosis pili promote adhesion to and invasion of THP-1 macrophages. Japanese Journal of Infectious Diseases, 67(6), 476–478.
Richaud, C., Mengin-Lecreulx, D., Pochet, S., Johnson, E. J., Cohen, G. N., & Marliere, P. (1993). Directed evolution of biosynthetic pathways recruitment of cysteine thioethers for constructing the cell wall of Escherichia coli. Journal of Biological Chemistry, 268(36), 26827–26835.
Rizvi, A., Shankar, A., Chatterjee, A., More, T. H., Bose, T., Dutta, A., et al. (2019). Rewiring of metabolic network in Mycobacterium tuberculosis during adaptation to different stresses. Frontiers in Microbiology, 10, 2417.
Romain, F., Horn, C., Pescher, P., Namane, A., Riviere, M., Puzo, G., et al. (1999). Deglycosylation of the 45/47-kilodalton antigen complex of Mycobacterium tuberculosis decreases its capacity to elicit in vivo or in vitro cellular immune responses. Infection and Immunity, 67(11), 5567–5572.
Ryndak, M. B., Singh, K. K., Peng, Z., & Laal, S. (2015). Transcriptional profile of Mycobacterium tuberculosis replicating in type II alveolar epithelial cells. PLoS ONE, 10(4), e0123745–e0123745.
Sambandamurthy, V. K., Wang, X., Chen, B., Russell, R. G., Derrick, S., Collins, F. M., et al. (2002). A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nature Medicine Journal, 8(10), 1171–1174.
Scapin, G., & Blanchard, J. S. (1998). Enzymology of bacterial lysine biosynthesis. Advances in Enzymology and Related Areas of Molecular Biology, 72, 279–324.
Schneeberger, E., & Lynch, R. (1997). Airway and alveolar epithelial cell junctions. The Lung. Scientific Foundations, Crystal. In: R. G., West, J. B., Weibel, E. R., Barnes, P. J., (Eds). Lippincott-Raven, Philadelphia.
Shellie, R., Marriott, P., & Morrison, P. (2001). Concepts and preliminary observations on the triple-dimensional analysis of complex volatile samples by using GC× GC− TOFMS. Analytical Chemistry, 73(6), 1336–1344.
Shkurupiy, V. A., Kim, L. B., Nikonova, I. K., Potapova, O. V., Cherdantseva, L. A., & Sharkova, T. V. (2013). Hydroxyproline content and fibrogenesis in mouse liver and lungs during the early stages of BCG granulomatosis. Bulletin of Experimental Biology and Medicine, 154(3), 299–302.
Schymanski, E. L., Jeon, J., Gulde, R., Fenner, K., Ruff, M., Singer, H. P., et al. (2014). Identifying small molecules via high resolution mass spectrometry: Communicating confidence. Environmental Science and Technology, 48, 2097–2098.
Sosunov, V., Mischenko, V., Eruslanov, B., Svetoch, E., Shakina, Y., Stern, N., et al. (2007). Antimycobacterial activity of bacteriocins and their complexes with liposomes. Journal of Antimicrobial Chemotherapy, 59(5), 919–925.
Stover, C. K., de la Cruz, V. F., Fuerst, T. R., Burlein, J. E., Benson, L. A., Bennett, L. T., et al. (1991). New use of BCG for recombinant vaccines. Nature, 351(6326), 456–460.
Sullivan, G. M., & Feinn, R. (2012). Using effect size-or why the P value is not enough. Journal of Graduate Medical Education, 4(3), 279–282.
van den Berg, R. A., Hoefsloot, H. C., Westerhuis, J. A., Smilde, A. K., & van der Werf, M. J. (2006). Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics, 7(1), 142.
van Kraaij, C., de Vos, W. M., Siezen, R. J., & Kuipers, O. P. (1999). Lantibiotics: biosynthesis, mode of action and applications. Natural Product Reports, 16(5), 575–587.
Vasstrand, E., Jensen, H. B., & Miron, T. (1980). Microbore single-column analysis of amino acids and amino sugars specific to bacterial cell wall eptidoglycans. Analytical Biochemistry, 105(1), 154–158.
Voet, D., Voet, J. G., & Pratt, C. W. (2016). Fundamentals of Biochemistry: Life at the Molecular Level. New Jersey, Newyork: John Wiley & Sons.
Warner, D. F. (2014). Mycobacterium tuberculosis metabolism. Cold Spring Harbor Perspectives in Medicine, 5(4), a021121.
Weber, H. U., Fleming, J. F., & Miquel, J. (1982). Thiazolidine-4-carboxylic acid, a physiologic sulfhydryl antioxidant with potential value in geriatric medicine. Archives of Gerontology and Geriatrics, 1(4), 299–310.
WHO (2019). World Health Organisation, Global Tuberculosis Report 2019. https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1. Accessed 29/10 2019.
Wishart, D. S., Feunang, Y. D., Marcu, A., Guo, A. C., Liang, K., Vazquez-Fresno, R., et al. (2018). HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Research, 46(D1), D608–d617.
Zhang, D., Li, J., Wang, F., Hu, J., Wang, S., & Sun, Y. (2014). 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Letters, 355(2), 176–183.
Zhong, L., Zhou, J., Chen, X., & Yin, Y. (2016). Serum metabolomic study for the detection of candidate biomarkers of tuberculosis. International Journal of Clinical and Experimental Pathology, 9(3), 3256–3266.
This study was funded by MP’s South African National Research Foundation CPRR Grant 105841 Grantholder-linked bursary and project running costs, and a University of KwaZulu-Natal College of Health Sciences scholarship.
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KSR declares that she has no conflict of interest. DLT declares he has no conflict of interest. DB declares she has no conflict of interest. MVR declares she has no conflict of interest. BP declares he has no conflict of interest. MP declares she has no conflict of interest.
The study was approved by the South African Biomedical Research Ethics Council (BE255/17).
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Reedoy, K.S., Loots, D.T., Beukes, D. et al. Mycobacterium tuberculosis curli pili (MTP) is associated with significant host metabolic pathways in an A549 epithelial cell infection model and contributes to the pathogenicity of Mycobacterium tuberculosis. Metabolomics 16, 116 (2020). https://doi.org/10.1007/s11306-020-01736-5
- M. tuberculosis curli pili
- A549 epithelial cells