Co-infection of Mycobacterium tuberculosis and Mycobacterium leprae in human archaeological samples: a possible explanation for the historical decline of leprosy

Both leprosy and tuberculosis were prevalent in Europe during the first millennium but thereafter leprosy declined. It is not known why this occurred, but one suggestion is that cross-immunity protected tuberculosis patients from leprosy. To investigate any relationship between the two diseases, selected archaeological samples, dating from the Roman period to the thirteenth century, were examined for both Mycobacterium leprae and Mycobacterium tuberculosis DNA, using PCR. The work was carried out and verified in geographically separate and independent laboratories. Several specimens with palaeopathological signs of leprosy were found to contain DNA from both pathogens, indicating that these diseases coexisted in the past. We suggest that the immunological changes found in multi-bacillary leprosy, in association with the socio-economic impact on those suffering from the disease, led to increased mortality from tuberculosis and therefore to the historical decline in leprosy.     

Flexibility of metal binding sites in proteins on a database scale

Protein metal binding sites in the pre-bound (apo) state, and their rearrangements upon metal binding were not analyzed previously at a database scale. Such a study may provide valuable information for metal binding site prediction and design. A high resolution, nonredundant dataset of 210 metal binding sites was created, containing all available representatives of apo-holo pairs for the most populated metals in the PDB. More than 40% of the sites underwent rearrangements upon metal binding. In 30 cases rearrangements involved the backbone. The tendency for side-chain rearrangement inversely correlates with the number of first-shell residues. Analysis of side-chain reorientations as a result of metal binding showed that in 95% of the rigid-backbone binding sites at most one side chain moved. Thus, in general, part of the first coordination shell is already in place in the pre-bound form. The frequencies of side-chain reorientation directly correlated with metal ligand flexibility and solvent accessibility in the apo state.     

Leishmania major: solid phase radioimmunoassay for antibody detection in human cutaneous leishmaniasis

A radioimmunoassay for the quantitative determination of antileishmanial antibody in sera from patients suffering from cutaneous leishmaniasis was developed. The assay, using as antigen either the soluble fraction from freeze-thawed sonicated Leishmania major (LRC-L137) promastigotes or a carbohydrate-lipid containing fraction obtained by extraction with hexane-isopropanol, was shown to be sensitive and reproducible. The sera of 95 patients were examined. These were from patients with cutaneous leishmaniasis (26 from the Jordan Valley and 13 from Sinai), kala-azar (9), malaria (24), schistosomiasis (10), toxoplasmosis (5), and leprosy (8); controls were 37 normal human sera. No significant antigen dependent differences were observed using sera from cutaneous leishmaniasis patients, although differences in the immunological response were observed between the two populations of these patients. Antileishmanial activity was not detected in sera from patients with malaria, schistosomiasis, or toxoplasmosis. Although sera from leprosy patients crossreacted with the carbohydrate-lipid containing fraction, it was nevertheless more strain specific than freeze thawed sonicated L. major.