AI Article Synopsis
- * Researchers created chicken-derived antibodies (scFv) that could react to these different types of MA and tested their ability to cross-react with cholesterol.
- * The study found that certain antibody configurations showed weak cross-reactivity with cholesterol, particularly those recognizing trans-keto MA, suggesting these antibodies could be useful for diagnosing tuberculosis.
Article Abstract
Mycolic acids (MA) are major, species-specific lipid components of Mycobacteria and related genera. In Mycobacterium tuberculosis, it is made up of alpha-, methoxy- and keto-MA, each with specific biological functions and conformational characteristics. Antibodies in tuberculosis (TB) patient sera respond differently towards the three MA classes and were reported to cross-react with cholesterol. To understand the antigenicity and cholesterol cross-reactivity of MA, we generated three different chicken -derived phage-displayed single-chain variable fragments (scFv) that reacted similarly towards the natural mixture of MA, but the first recognized all three classes of chemically synthetic MAs, the second only the two oxygenated types of MAs and the third only methoxy MA. The cholesterol cross-reactivity was investigated after grafting each of the three scFv types onto two configurations of constant chain domains-CH1-4 and CH2-4. Weak but significant cross-reactivity with cholesterol was found only with CH2-4 versions, notably those two that were also able to recognize the trans-keto MA. The cholesteroid nature of mycobacterial mycolic acids therefore seems to be determined by the trans-keto MA subclass. The significantly weaker binding to cholesterol in comparison to MA confirms the potential TB diagnostic application of these antibodies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084858 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200298 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Four novel nontuberculous mycobacteria species: sp. nov., sp. nov., sp. nov. and sp. nov. revived from a historical Danish strain collection.
Int J Syst Evol Microbiol
January 2025
International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.
Four novel nontuberculous mycobacteria were discovered from a historical strain collection at the International Reference Laboratory of Mycobacteriology at Statens Serum Institut in Copenhagen, Denmark. Phylogenetic analysis combining the 16S , internal transcribed spacer and 23S elements, as well as a single-copy core-gene (, , and ) analysis of these freeze-dried mycobacteria, clinically isolated from gastric lavage samples between 1948 and 1955, showed to be associated with type strains grouping within the Terra and Fortuitum-Vaccae clade. Phenotypic characteristics, biochemical properties and fatty acid and mycolic acid profiles supported the classification as novel strains.
View Article and Find Full Text PDFManipulation and Structural Activity of AcpM in .
Biochemistry
December 2024
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
(Mtb) is a leading cause of death, with an escalating global occurrence of drug-resistant infections that are partially attributed to cell wall mycolic acids derived from type II fatty acid biosynthesis (FAS-II). Here, the central acyl carrier protein, AcpM, contributes to the regulation of complex and specific protein-protein interactions (PPIs), though the orchestration of these events remain largely unresolved due to unique features of AcpM. Limitations include complexities in generating modified AcpM in a single state.
View Article and Find Full Text PDFDomain architecture of the MabR (), a member of the PucR transcription factor family.
Heliyon
November 2024
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development, Faculty of Pharmacy, Université Libre de Bruxelles, Belgium.
MabR (), a PucR-type transcription factor, plays a crucial role in regulating mycolic acid biosynthesis in . To understand its regulatory mechanisms, we determined the crystal structures of its N-terminal and C-terminal domains. The N-terminal domain adopts a globin-like fold, while the C-terminal domain comprises an α/β GGDEF domain and an all-α effector domain with a helix-turn-helix DNA-binding motif.
View Article and Find Full Text PDFApplication of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis.
Trop Med Infect Dis
November 2024
Future Production: Chemicals, Council for Scientific and Industrial Research, Pretoria 0081, South Africa.
Article Synopsis
- - Patient loss to follow-up due to expensive and centralized diagnostics for tuberculosis is a major challenge, stressing the need for a more accessible testing method.
- - Current biomarkers, specifically antibodies against mycolic acids in mycobacterial cell walls, show potential but are hard to detect with typical rapid tests because they are of low affinity.
- - Researchers have developed a new method for detecting mycolic acid antibodies using engineered monoclonal antibodies, leading to the creation of a novel lateral flow immunoassay called MALIA, which shows promise for practical tuberculosis testing.
Advancements and challenges in tuberculosis drug discovery: A comprehensive overview.
Microb Pathog
January 2025
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India. Electronic address:
Tuberculosis continues to pose a health challenge causing the loss of millions of lives despite the existence of multiple drugs, for treatment. The emergence of drug-resistant strains has made the situation more complex making it increasingly difficult to fight against this disease. This review outlines the challenges associated with TB drug discovery, the nature of Mycobacterium tuberculosis shedding light on the mechanisms that lead to treatment failure and antibiotic resistance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!