Molecular studies are shedding new light on the pathogenesis of human typhoid fever, which is still a very common disease in developing countries. For example, the total genome DNA sequence has recently been determined for a multiple-drug-resistant Salmonella typhi, the serotype that is the cause of typhoid fever. The genome sequence showed many distinguishing features, including clusters of S typhi specific genes and a large number--over 200--of pseudogenes. This information, together with other molecular studies, has provided vital clues in several important areas of typhoid biology. We have new insights into the mechanisms underpinning the human host specificity of S typhi, and have exploitable new routes to improved diagnostics and a better understanding of the epidemiology of the disease.

Anti-Bacterial Agents↗

PubMed2002

Complete sequence and organization of pBtoxis, the toxin-coding plasmid of Bacillus thuringiensis subsp. israelensis.

The entire 127,923-bp sequence of the toxin-encoding plasmid pBtoxis from Bacillus thuringiensis subsp. israelensis is presented and analyzed. In addition to the four known Cry and two known Cyt toxins, a third Cyt-type sequence was found with an additional C-terminal domain previously unseen in such proteins. Many plasmid-encoded genes could be involved in several functions other than toxin production. The most striking of these are several genes potentially affecting host sporulation and germination and a set of genes for the production and export of a peptide antibiotic.

Bacillus thuringiensis↗

PubMed1999

New insertion sequences and a novel repeated sequence in the genome of Mycobacterium tuberculosis H37Rv.

The genome sequence of Mycobacterium tuberculosis H37Rv was found to contain 56 loci with homology to insertion sequences (ISs). As well as the previously described IS6110, IS1081, IS1547 and IS-like elements, new ISs belonging to the IS3, IS5, IS21, IS30, IS110, IS256 and ISL3 families were identified. In addition, six ISs created a grouping of their own to form a new family (the IS1535 family). Elements with similarity to ISs in other actinomycetes were identified, suggesting the movement of ISs between related genera. The location of ISs on the chromosome revealed that an approximately 600 kb region close to the origin of replication lacks ISs, pointing to the possible detrimental effect of insertions in this area. Analysis of the distribution of ISs through the tubercle strains Mycobacterium africanum, M. microti, M. bovis, M. bovis BCG Pasteur, M. tuberculosis H37Ra, M. tuberculosis CSU#93 and 29 clinical isolates revealed that only IS1532, IS1533, 1S1534, and IS1561' were absent from some of the strains tested. A novel repeated sequence, the REP13E12 family, is described that is present in seven copies on the M. tuberculosis H37Rv chromosome and which contains a probable phage attachment site. This study therefore offers an insight into the possible role of ISs and repetitive elements in the evolution of the M. tuberculosis genome, as well as identifying genetic markers that may be useful for phylogenetic and epidemiological analysis of the tubercle complex.

Base Sequence↗

PubMed1998

Selection and characterization of mercury-independent activation mutants of the Tn501 transcriptional regulator, MerR.

MerR is the transcriptional regulator of the mercury-resistance (mer) operon of transposon Tn501, acting at the mer promoter as both an activator in the presence of mercuric salts and a repressor in their absence. This paper reports a method for selection of constitutive activator mutants, which activate transcription in the absence of HgII, and the characterization of these MerRAC proteins. At least two mutations in the MerR protein were found necessary for strong mercury-independent activation, and these mutations lie in the C-terminal two-thirds of the MerR protein near the HgII-binding cysteines. A triple mutation was shown to increase activation over the corresponding double mutations. All mutant proteins caused further activation in the presence of HgII. The data support a mechanism in which a conformational change of one or both MerR subunits in the homodimer drives a distortion of DNA bound to a helix-turn-helix structure in the N-terminal region. A mutation in this putative helix-turn-helix region severely reduced both the repressor and activator functions of MerR.

Bacterial Proteins↗