Anti Mycobacterium avium subsp. paratuberculosis heat shock protein 70 antibodies in the sera of Sardinian patients with multiple sclerosis.

 Heat shock protein (HSP) family members are highly conserved in both prokaryotic and eukaryotic organisms and are known to be immunodominant antigens in many bacteria. In particular, HSP70 has been linked to multiple sclerosis (MS), even if the available data are contradictory. Since different studies conducted on Sardinian subjects, have linked Mycobacterium avium subspecies paratuberculosis (MAP) presence to MS disease, and in view of the fact that human HSP70 is highly homologue to the majority of mycobacterial HSP70 proteins, we searched for anti-MAP HSP70 antibodies in the sera of 268 MS patients and 231 age and sex-matched healthy controls (HCs). All the subjects enrolled in the study were from Sardinia, which is an excellent setting for investigation since it has one of the highest prevalence of MS worldwide. HSP70 detection was carried out using ELISA methodology. A statistically significant difference was found between MS patients and HCs when analyzing the humoral response mounted against MAP HSP70 protein. Our study confirms that mycobacterial HSP70 might be involved in MS, and provides another piece of evidence sustaining the role played by MAP in MS in the context of Sardinian population.

Vitamin C Slays TB Bacteria | The Scientist Magazine®

"High doses of vitamin C can rapidly wipe out entire populations of drug-resistant strains of the bacteria that cause tuberculosis (TB) by inducing a chemical reaction that produces high levels of DNA-damaging oxidative radicals, according to a study published today (May 21) in Nature Communications."

Wolf in sheep's clothing: Uncovering how deadly bacteria trick the immune system / UCLA Newsroom

In a study published online Feb. 28 in the journal Science, UCLA researchers demonstrate that certain cunning bacteria — including the type that causes tuberculosis — can pretend to be viruses when infecting humans, allowing them to hijack the body's immune response so that they can hide out, unhindered, inside our cells. The findings may also help explain how viral infections like the flu make us more susceptible to subsequent bacterial infections such as pneumonia.

Medicinal 'toothbrush tree' yields antibiotic to treat TB in new way

The compound under research, diospyrin, binds to a novel site on a well-known enzyme, called DNA gyrase, and inactivates the enzyme. DNA gyrase is essential for bacteria and plants but is not present in animals or humans. It is established as an effective and safe drug target for antibiotics.

Are Mycobacterium avium subsp. paratuberculosis and Epstein-Barr virus triggers of multiple sclerosis in Sardinia?

Sardinia acts as an ideal setting for multiple sclerosis (MS) studies because its prevalence of MS is one of the highest worldwide. Several pathogens have been investigated amongst 119 Sardinian MS patients and 117 healthy controls to determine whether they might have a role in triggering MS in genetically predisposed individuals. Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein Barr virus DNA were detected in 27.5% and 17.3%, respectively, of the MS patients. Moreover an extremely high humoral immune response against MAP recombinant protein MAP FprB (homologous to human myelin P0) was observed, whereas no significant results were found against Mycobacterium tuberculosis FprA and Helicobacter pylori HP986 protein.

Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimicry against host: implications in autoimmune pathogenesis.

Molecular mimicry between microbial antigens and host-proteins is one of the etiological enigmas for the occurrence of autoimmune diseases. T cells that recognize cross-reactive epitopes may trigger autoimmune reactions. Intriguingly, autoimmune diseases have been reported to be prevalent in tuberculosis endemic populations. Further, association of Mycobacterium tuberculosis (M. tuberculosis) has been implicated in different autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Although, in silico analyses have identified a number of M. tuberculosis specific vaccine candidates, the analysis on prospective cross-reactive epitopes, that may elicit autoimmune response, has not been yet attempted. Here, we have employed bioinformatics tools to determine T cell epitopes of homologous antigenic regions between M. tuberculosis and human proteomes.

RESULTS:

Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection.

CONCLUSIONS:

The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.

Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.

Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER) stress mediated apoptosis in mycobacteria infected macrophages.

METHODOLOGY/PRINCIPAL FINDINGS:

Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response.

CONCLUSION/SIGNIFICANCE:

These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria.