Gloria G Guerrero M*

Academic Unit of Biological Sciences. Francisco García Salinas Autonomous University of Zacatecas. Preparatoria Avenue, S/N. Agronómicas Neighborhood. Zacatecas, Zacatecas, Mexico

*Corresponding Author: Gloria G Guerrero M, Academic Unit of Biological Sciences. Francisco García Salinas Autonomous University of Zacatecas. Preparatoria Avenue, S/N. Agronómicas Neighborhood. Zacatecas, Zacatecas, Mexico.

Received: April 16 2025; Published: April 21, 2025

Abstract

Tuberculosis, an ancient infectious disease caused by Mycobacterium tuberculosis (MTb), a Gram-positive bacillus, is a public health problem because 95% of infected people develop latent tuberculosis, while 5% develop active disease. The situation is worsen by the increase in multidrug resistance (MDR), co-morbidities and the lack of a more effective vaccine, which prolongs and induces long-lasting memory immune responses in young older adults. The development of pharmacological and immunotherapies depends on an understanding the spectrum of the disease, the genetic susceptibility to mycobacterial infection and evasion the mechanisms developed by Mtb against the microbicide action of the host. The three-layered mycobacterial envelope is roughly seen from the outside to the inside: -A surface layer, -the capsule, composed of polysaccharides and proteins, present only in the pathogenic species. The mycomembrane (MM), composed of proteins and long fatty acids (long chain mycolic acids from C60-C90) with free intercalated glycolipids and covalently linked to arabinogalactan and peptidoglycan layer, similar to those of Gram-negative bacteria, and the phospholipid bilayer inner classical plasma membrane. These components are pathogen-associated molecular patterns (PAMPs) that are recognized by patterns of receptor recognition (PPRs) on the surface of antigen-presenting cells (macrophages, dendritic cells). This is the first interaction between host and pathogen that results in effective activation and immune modulation of the host response. The pathways involved in the biosynthesis of the outer and inner membranes, including the waxy cell wall of the mycomembrane, represent immunological or pharmacological targets for diagnosis and treatment. Here is an overview of the characteristics of the mycobacterial cell envelope.

Keywords: Waxy Cell Envelope; Pathogenic; Non-Pathogenic; Mycobacteria; Antibiotics; Protection against

References

1. World Health Organization. Global Tuberculosis Report. World Health Organization (2023).
2. Global tuberculosis report. Geneva: World Health Organization (2023).
3. Behr MA., et al. “Is Mycobacterium tuberculosis infection life long?” BMJ 367 (2019): 15770.
4. O'Garra A., et al. “The immune response in tuberculosis”. Annual Review of Immunology 31 (2013): 475-527.
5. da Costa AC., et al. “Recombinant BCG: innovations on an old vaccine. Scope of BCG strains and strategies to improve long-lasting memory”. Frontiers in Immunology 5 (2014): 152.
6. Zumla A and Maeurer M. “Host-Directed therapies for tackling multi-drug-resistant tuberculosis: learning from the Pasteur-Bechamp debates”. Clinical Infectious Diseases 61 (2015): 1432-1438. 
7. Udwada ZF., et al. “Totally drug-resistant tuberculosis in Inida”. Clinical Infectious Diseases 54 (2012): 579-581.
8. Adams O., et al. “The CRyPTIC Consortium., Fowler PW., Lea MS., and Newstead S. Cryo-EM structure and resistance landscape of M. landscape of M. tuberculosis MmpL3: an emergent target”. Structure 29 (2021): 1182-1191e4. 
9. Daneshvar P., et al. “COVID-19 and tuberculosis coinfection: An overview of case reports/case series and meta- analysis of prevalence studies”. Heliyon 9 (2023):
10. Booysen P., et al. “Immune interaction between SARS-CoV-2 and Mycobacterium tuberculosis”. Frontiers in Immunology 14 (2023):
11. Casanova JL., et al. “From rare disorders of immunity to common determinants of infection: Following the mechanistic thread”. Cell 185 (2022): 3086-3103.
12. Laval T., et al. “Not too fat to fight: The emerging role of macrophage fatty acid metabolism in immunity to Mycobacterium tuberculosis”. Immunological Reviews 301 (2021): 84-97.
13. Chandra P., et al. “Immune evasion and provocation by Mycobacterium tuberculosis”. Nature Reviews Microbiology 11 (2022): 750-767.
14. Ortalo-Magne A., et al. “Identification of the surface-exposed lipids on the cell envelopes of Mycobacterium tuberculosis and other mycobacterial species”. Journal of Bacteriology 178 (1996): 456-461.
15. Chiaradia L., et al. “Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane”. Scientific Report 7 (2017): 12807-12825.
16. Dulberger ChL., et al. “The mycobacterial cell envelope - a moving target”. Nature Reviews Microbiology 8 (2020): 47-59.
17. Wang S., et al. “Arabinosyl transferase C mediates multiple drugs intrinsic resistance by altering cell envelope permeability in Mycobacterium abscessus”. Microbiology Spectrum 10 (2022):
18. Berry PRM., et al. “An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis”. Letter to Nature 466 (2010): 973-997.
19. Guerrero GG., et al. “Clinical, and Diagnostic characteristics of an unsuspected course of urinary Tuberculosis: A Brief Report”. ASM 5 (2022): 1-8.
20. Zhang W., et al. “Genome sequencing and analysis of BCG strains”. PLOS One 8 (2013):
21. Lu Y., et al. “Deletion of the Mycobacterium tuberculosis cyp138 gene leads to changes in membrane-related lipid composition and antibiotic susceptibility”. Frontiers in Microbiology 15 (2024):
22. Jackson M., et al. “Transporters Involved in the biogénesis and functionalization of the mycobacterial cell envelope”. Chemical Reviews 121 (2021): 5124-5157.
23. Batt SM., et al. “The thick waxy coat of micobacteria, a protectivelayer against antibiotics and the host’s immune system”. Biochem 477 (2020): 1983-2006.
24. Rahlwes KC., et al. “Cell Wall and membranes of actinobacteria”. Subcellular Biochemistry 92 (2019): 417-469.
25. Bhat ZS., et al. “The cell wall: A versatile fountain of drug targets in Mycobacterium tuberculosis”. Biomedicine and Pharmacotherapy 95 (2017): 1520-1534.
26. Chalut C. “MmpL transporter-mediated export of cell-wall associated lipids and siderophores in mycobacteria”. Tuberculosis (Edinb) (2016): 32-45. 
27. Singh P., et al. “Cell envelope lipids in the pathophysiology of Mycobacterium tuberculosis”. Future Microbiology 13 (2018): 689-710.
28. Christensen H., et al. “Lipid domains of mycobacteria studied with fluorescent molecular probes”. Molecular Microbiology 31 (1999): 1561-1572.
29. Burbaud S., et al. “Trehalose polyphleates are produced by a glycolipid biosynthetic pathway conserved across phylogenetically distant mycobacteria”. Cell Chemical Biology 23 (2016): 278-289.
30. Daffé M., et al. “Genetics of capsular polysaccharides and cell envelope (Glyco) lipids”. Microbiology Spectrum 2 (2014):
31. Daffé M and Marrakchi H. “Unraveling the structure of the mycobacterial nvelope”. Microbiology Spectrum 7 (2019): 7-14.
32. Schami A., et al. “Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host”. Frontiers in Cellular and Infection Microbiology 13 (2018):
33. Llorens-Fons M., et al. “Trehahalose polyphleates, external cell Wall lipids in Mycobacterium abscessus, are associated with the formation of clumps with cording morphology, which have been associated with virulence”. Frontiers in Microbiology 8 (2017): 1402-1417.
34. Madacki J., et al. “Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria”. Journal of Biological Chemistry 293 (2018): 5172-5184.
35. Purwantini E and Mukhopadhyay. “Rv132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent hydroxymycolic acid dehydrogenase”. PLOS ONE 8 (2013):
36. Takayama K., et al. “Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis”. Clinical Microbiology Reviews 18 (2005): 81-101.
37. Yagi T., et al. “Polymerization of mycobacterial arabinogalactan and ligation to peptidoglycan”. Journal of Biological Chemistry 278 (2003): 26497-26504.
38. Minnikin DE., et al. “Mycolic acids patterns of some species of Mycobacterium”. Archives of Microbiology 139 (1984): 225-231.
39. Dubnau E., Chan J., Raynaud C., Mohan VP., Laneelle MA., et al. Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice”. Molecular Microbiology 36 (2000): 630-637.
40. Jankute M., et al. “Assembly of the Mycobacterial Cell Wall”. Annual Review of Microbiology 69 (2015): 405-423.
41. Holzheimer M., et al. “Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis”. Chemical Reviews 121 (2021): 9554-9643.
42. Yuan Y., et al. “A common mechanism for the biosynthesis of methoxy and cyclopropyl mycolic acids in Mycobacterium tuberculosis”. Proceedings of the National Academy of Sciences of the United States of America 93 (1996): 12828-12833.
43. Sambandan D., et al. “Keto-mycolic acid-dependent Pellicle formation confers tolerance to drug sensitive Mycobacterium tuberculosis”. MBio 4 (2013): e00222-13.
44. Vander Becken S., et al. “Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern”. European Journal of Immunology 41 (2011): 450-460.
45. Beukes M., et al. “Structure-function relationships of the antigenicity of mycolic acids in tuberculosis patients”. Chemistry and Physics of Lipids 163 (2010): 800-808.
46. Rao V., et al. “Transcyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence”. Journal of Clinical Investigation 116 (2010): 1660-1667.
47. Onwueme KC., et al. “The dimycocerosate ester polyketide virulence factors of mycobacteria”. Progress in Lipid Research 44 (2005): 259-302.
48. Van Schie L., et al. “Exploration of Synergistic Action of Cell Wall-Degrading Enzymes against Mycobacterium tuberculosis”. Antimicrobial Agents and Chemotherapy 65 (2021):
49. Pirson Ch., et al. “Differential effects of Mycobacterium bovis-derived polar and apolar lipid fractions on bovine innate immune cells”. Veterinay Research 43 (2012): 54-65.
50. Minnikin DE., et al. “Thin-layer chromatography of methanolysates of mycolic acidcontaining bacteria”. Journal of Chromatography A 188 (1980): 221-233.
51. Engel KM., et al. “A new update of MALDI-TOF mass spectrometry in lipid research”. Progress in Lipid Research 86 (2022):

Citation

Citation: Gloria G Guerrero M. “The Waxy Cell Envelope of Pathogenic and Non-Pathogenic Mycobacteria: Resistance to Antibiotics and Protection against Host Response. An Overview".Acta Scientific Microbiology 8.5 (2025): 41-48.

Copyright

Copyright: © 2025 Gloria G Guerrero M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.