Native M. Tuberculosis LAM antigen

Name: Native M. Tuberculosis LAM antigen
SKU: DAGA-168
Rating: 5 (1 reviews)

Lipoarabinomannan (LAM), extracted from Mycobacterium tuberculosis

COA

SDS

Datasheet

Summary

Target

M. tuberculosis LAM

Nature

Native

Tag/Conjugate

N/A

Molecular Weight

37 kDa

Purity

> 90 % as determined by HPLC

Format

Liquid

Concentration

1 mg/mL

Buffer

Supplied in PBS

Preservative

None

Storage

Store at -20°C

Ship

Wet ice

Introduction

Mycobacterium tuberculosis Lipoarabinomannan, commonly known as LAM, is a glycolipid that is part of the cell wall of Mycobacterium tuberculosis, the bacterium responsible for causing tuberculosis (TB). LAM is an important virulence factor and plays a central role in the host-pathogen interaction during TB infection.

Keywords

Mycobacterium tuberculosis; Lipoarabinomannan; LAM

Citations

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Mycobacterium tuberculosis Rv3463 induces mycobactericidal activity in macrophages by enhancing phagolysosomal fusion and exhibits therapeutic potential

Hye-Soo Park, Yong Woo Back, Ki-Won Shin, Hyun Shik Bae, Kang-In Lee, Han-Gyu Choi, Seunga Choi, Hwang-Ho Lee, Chul Hee Choi, Jeong-Kyu Park, Hwa-Jung Kim

Sci Rep2019 MarPubMed ID: 30862819Read Article

Applications: Unspecified application

Reactive species: Unspecified reactive species

"Abstract: Macrophages are responsible for innate and adaptive immune response activation necessary for eliminating infections. Optimal activation of macrophages to phagocytize Mycobacterium tuberculosis is critical in anti-mycobacterial defense. Here, we identified a novel Rv3463 hypothetical protein that induces macrophage activation in Mtb culture filtrate. Recombinant Rv3463 activated mouse bone marrow-derived macrophages to induce the expression of surface molecules and secrete pro-inflammatory cytokines via the TLR2 and TLR4 pathways. Mitogen activated protein kinase, phospatidylinositol-4,5-bisphosphate 3-kinases, and the NF-κB signaling pathways are involved in Rv3463-mediated macrophage activation. Furthermore, Rv3463 induced bactericidal effects in Mtb-infected macrophages through phagosome maturation and phagolysosomal fusion enhanced by phospatidylinositol-4,5-bisphosphate 3-kinases and Ca2+ signaling pathways and exhibited therapeutic effects in a short-term Mtb-infection mouse model. Overexpression of Rv3463 in M. smegmatis caused rapid clearance of bacteria in macrophages and mice. Our study suggests that Rv3463 is a promising target for the development of post-exposure tuberculosis vaccines or adjunct immune-therapy."

Article snippet: Mtb LAM antigen (DAGA-168) was purchased from Creative Diagnostics (CD, Shirley, NY, U.S.A).

Incubate BMDMs with or without LAM pre-treatment for 30 minutes. (Hye-Soo Park, <i>et al</i>, 2019)

Figure 1. BMDMs were preincubated for 30min with or without 20μg/ml Mtb LAM or a mixture of LAM and Rv3463

Background

The native Mycobacterium tuberculosis lipoarabinomannan (LAM) antigen is a key component of the cell wall of the tuberculosis-causing bacterium, Mycobacterium tuberculosis. LAM is a complex glycolipid molecule that plays a crucial role in the pathogenesis of tuberculosis and interacts with the host immune system. It is considered a major virulence factor and a potential target for diagnostic and therapeutic interventions.
The structure of LAM is highly diverse and can vary depending on the strain and host immune response. It consists of a mannan backbone with arabinofuranose residues and various capping motifs, such as extra-mannoses, methylthio-D-xylose, or arabinofuranosides. These structural variations contribute to the immunomodulatory properties of LAM, influencing the host immune response and disease progression.

native-m.tuberculosis-lam-antigen.jpg Figure 1. Various lipoarabinomannan (LAM) structures characterized in Mycobacterial spp.
(Source: Kim, P. M. et al., 2018)

LAM has been extensively studied for its diagnostic potential in tuberculosis (TB). It has been detected in various clinical samples, including sputum, urine, serum, and cerebrospinal fluid. Several diagnostic assays, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow assays (LFAs), have been developed to detect LAM in patient samples. These assays offer the potential for rapid and sensitive detection of tuberculosis, particularly in individuals with advanced HIV infection or extrapulmonary TB. Furthermore, LAM has been investigated as a potential target for therapeutic interventions. It has been shown to modulate the host immune response, leading to immune evasion and persistence of the bacteria within the host. Targeting LAM with immunomodulatory drugs or antibodies could potentially enhance host immune responses and improve treatment outcomes.
Despite its diagnostic and therapeutic potential, challenges exist in utilizing LAM antigen. These include limitations in sensitivity, the complex and variable structure of LAM, and the potential interference of LAM with host immune responses. Ongoing research efforts aim to overcome these challenges and further explore the diagnostic and therapeutic applications of LAM.

Alternative Names

Native M. Tuberculosis LAM
Native Mycobacterium tuberculosis lipoarabinomannan
Native MTB lipoarabinomannan
Native MTB LAM
Native M. Tuberculosis lipoarabinomannan antigen
Native Mycobacterium tuberculosis lipoarabinomannan antigen
Native MTB lipoarabinomannan antigen
Native MTB LAM antigen

References

1. Kim P M, et al. Endothelial lineage-specific interaction of Mycobacterium tuberculosis with the blood and lymphatic systems. Tuberculosis. 2018, 111: 1-7.

Documents

pdf COA

pdf SDS

pdf Datasheet

M. tuberculosis Antibodies and Antigens

Infectious Disease Native Antigens

QA & Reviews

Q & A

Ask a Question

Q: Would you be able to tell me how the antigen is sourced/produced? Also how is the concentration of the antigen determined?

A: The LAM antigen is extracted from cultured M. Tuberculosis in BSL3 labs. The concentration is determined by the phenol-sulfuric acid method.

Customer Reviews

References

1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors

MOLECULES

Authors: Jian, Yanlin; Hulpia, Fabian; D. P. Risseeuw, Martijn; Forbes, He Eun; Caljon, Guy; Munier-Lehmann, Helene; I. M. Boshoff, Helena; Van Calenbergh, Serge

Abstract

A series ofMycobacterium tuberculosisTMPK (MtbTMPK) inhibitors based on a reported compound3were synthesized and evaluated for their capacity to inhibitMtbTMPK catalytic activity and the growth of a virulentM. tuberculosisstrain (H37Rv). Modifications of the scaffold of3failed to afford substantial improvements inMtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of3resulted in compound21jwith improvedMtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of21jto thepara-position afforded isomer21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 mu M).

BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

Authors: Suresh, Parasmal; Biswas, Lalitha; Prasad, Vinitha; Kumar, Anil; Sivadas, Suchitra; Khan, Sadia; Biswas, Raja

Abstract

MPT64 is a 24-kDa immunogenic protein that is widely used as a diagnostic marker for the differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous Mycobacterium (NTM). Unlike Mycobacterium bovis, Bacillus Calmette-Guerin(BCG) vaccine strains with RD2 deletion do not secrete MPT64. Culture isolates from infections due to these strains may be falsely identified as nontuberculous Mycobacterium in the absence of clinical correlation. Here, we present one case each of BCG adenitis and osteitis, both of which were considered as MPT64 card-negative Mycobacterium spp. (i.e., NTM) and were later identified as M. bovis BCG Danish 1331 strain. The first case was a 4-month-old female infant admitted with swollen lymph nodes in the left supraclavicular and the left axillary region of 1 month duration. The second case was of a 1-year-and-5-month-old male child who presented with a limp on the left leg and soft tissue swelling of 1 month duration on the anterolateral aspect of the left knee joint. In both cases, BCG vaccine was administered at birth on the left deltoid region and had healed without any complication. Clinical samples in both cases were positive by Xpert tuberculosis/RIF for MTBC, and cultures grew acid-fast bacilli which were negative by MPT64 assay. The clinical implication of infections due to M. bovis BCG is immense as they are inherently resistant to pyrazinamide, and the presence of disseminated BCG infection in young children is a hallmark of serious immune deficiency which needs to be ruled out.

Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?

Frontiers in Microbiology

Authors: Flores J, Cancino J C, Chavez-Galan L.

Abstract

Tuberculosis (TB) is still a severe public health problem; the current diagnostic tests have limitations that delay treatment onset. Lipoarabinomannan (LAM) is a glycolipid that is a component of the cell wall of the bacillus Mycobacterium tuberculosis, the etiologic agent of TB. This glycolipid is excreted as a soluble form in urine. The World Health Organization has established that the design of new TB diagnostic methods is one of the priorities within the EndTB Strategy. LAM has been suggested as a biomarker to develop diagnostic tests based on its identification in urine, and it is one of the most prominent candidates to develop point-of-care diagnostic test because urine samples can be easily collected. Moreover, LAM can regulate the immune response in the host and can be found in the serum of TB patients, where it probably affects a wide variety of host cell populations, consequently influencing the quality of both innate and adaptive immune responses during TB infection. Here, we revised the evidence that supports that LAM could be used as a tool for the development of new point-of-care tests for TB diagnosis, and we discussed the mechanisms that could contribute to the low sensitivity of diagnostic testing.

Application of lipoarabinomannan antigen in tuberculosis diagnostics: current evidence

Postgraduate Medical Journal

Authors: Sarkar P, Biswas D, Sindhwani G, et al.

Abstract

Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for tuberculosis (TB). We aimed to assimilate the current evidence regarding the diagnostic performance of LAM assays and to ascertain their clinical indication in settings with high and low prevalence of HIV-TB co-infection. Owing to suboptimal sensitivity, the urinary LAM assays are unsuitable as general screening tests for TB. However, unlike traditional diagnostic methods, they demonstrate improved sensitivity in HIV-TB co-infection which further increases with low CD4 counts. Accordingly, these assays are indicated as rule-in tests for TB in patients with advanced HIV-induced immunosuppression, and facilitate the early initiation of antituberculous treatment in them. They also offer incremental sensitivity and specificity when used as adjunct tests to smear microscopy and chest radiography in HIV-TB co-infection. They obviate the biohazards associated with sputum samples and provide an alternative diagnostic tool in sputum-scarce patients. Notwithstanding these advantages, the specificity of these assays is variable, which is mostly attributable to misclassification bias and cross-reactivity with non-tuberculous mycobacteria or other commensal flora. Furthermore, the inability to detect low titres of antigen in HIV-uninfected patients makes these assays unsuitable for use in settings with a low HIV prevalence. Future research targeted towards inclusion of specific monoclonal antibodies and more sensitive immunoassay platforms might help to improve the diagnostic performance of these assays and extend their applicability to the general population of patients with TB.