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Abstract Background The 19 kDa lipoprotein of Mycobacterium tuberculosis (MTB) is an important target of the innate immune response. To investigate the effect of post-translation modification of this protein on innate recognition in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19 kDa gene (Δ19) and complemented this strain by reintroduction of the 19 kDa gene into the chromosome as a single copy to produce Δ19::19. We also reintroduced the 19 kDa gene in two modified forms that lacked motifs for acylation (Δ19::19NA) and O-glycosylation (Δ19::19NOG). Results Both acylation and O-glycosylation were necessary for the protein to remain within the cell. IL-1 Beta secretion from human monocytes was significantly reduced by deletion of the 19 kDa gene (p < 0.02). Complementation by the wild type, but not the mutagenised gene reversed this phenotype. The effect of deletion and complementation on IL-12p40 and TNF secretion was less marked with no statistically significant differences between strains. Although deletion of the 19 kDa reduced apoptosis, an effect that could also only be reversed by complementation with the wild type gene, the results were variable between donors and did not achieve statistical significance. Conclusion These results confirm in the context of the whole bacillus an important role for post-translational modification of the 19 kDa on both the cellular location and immune response to this protein.

Author(s): Hanif Esmail (corresponding author) [1, 2, 3]; Rachel P Lai [4]; Maia Lesosky [2, 5]; Katalin A Wilkinson [2, 4]; Christine M Graham [4]; Anna K Coussens [2]; Tolu [...]

Ethiopia is among the countries with the highest incidence of tuberculosis (TB) and has a yearly incidence of 261 cases/100,000 population. TB lymphadenitis in cervical lymph nodes (TBLN) accounts for [...]

Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop TB Partnership published "The global plan to stop TB: 2006-2015," which set out a vision of halving the prevalence of and mortality caused by the disease by 2015, followed by eliminating the disease as a public health problem by 2050. This vision depends on the development of improved diagnostics, simpler treatment, and more effective vaccination. Recently, active translational research pipelines directed toward each of these goals have been established, but improved understanding of the fundamental biology of this complex disease will prove to be the key to radical advances in TB control., Introduction Tuberculosis (TB) is today the second highest cause of death from an infectious disease worldwide, after HIV/AIDS (1), and is the biggest killer of people infected with HIV (reviewed [...]

Research has been conducted on transcriptional regulation of Mycobacterium tuberculosis heat-shock proteins. The study of this regulation has been carried out via the use of microarrays prepared by spotting DNA sequences, and the contribution of the regulatory circuits to the heat-shock response is discussed.

The author reviews the publications on rapid-growing non-pathogenic mycobacteria. The topics of interest include the approaches based on mycobacteria dissection at the DNA level and the mycobacterial genus in the post-genomic era.

Elevated expression of heat-shock proteins (HSPs) can benefit a microbial pathogen struggling to penetrate host defenses during infection, but at the same time might provide a crucial signal alerting the host immune system to its presence. To determine which of these effects predominate, we constructed a mutant strain of Mycobacterium tuberculosis that constitutively overexpresses Hsp70 proteins. Although the mutant was fully virulent in the initial stage of infection, it was significantly impaired in its ability to persist during the subsequent chronic phase. Induction of microbial genes encoding HSPs might provide a novel strategy to boost the immune response of individuals with latent tuberculosis infection., Author(s): Graham R. Stewart (corresponding author) [1]; Valerie A. Snewin [1]; Gerhard Walzl [2]; Tracy Hussell [2]; Peter Tormay [1]; Peadar O'Gaora [1]; Madhu Goyal [3]; Joanna Betts [4]; Ivor [...]

Research has been conducted on theMycobacterium tuberculosis pathogenesis. The identification of the M. tuberculosis genes that are required for intracellular survival within macrophages has been performed.

Results indicate multiple biosynthetic pathways for trehalose production in mycobacteria namely glucose 6-phosphate and UDP-glucose pathway, glycogen-like alpha (1-4)linked glucose polymer pathway, and maltose pathway.

Research was conducted to determine the action of fosfomycin on MurA enzyme and the effect of amino acid substitution on its activity. Results show that fosfomycin inhibits the enzyme and the inhibitory effect is altered when cysteine residue is replaced with aspartate-117.

KEY WORDS: tuberculosis, vaccines, drugs, mycobacteria, immunity CONTENTS INTRODUCTION Tuberculosis Other Mycobacterial Diseases BASIC BIOLOGY OF MYCOBACTERIAL INFECTION Stage 1. Initial Uptake of Bacteria Stage 2. T-Cell Responses Stage 3. [...]

Novel vectors, with selection based on expression of hygromycin resistance, facilitated the transformation of such mycobacterial species as Mycobacterium smegmatis and Mycobacterium bovis BCG. The hygromycin resistance vector exhibited greater efficiency than kanamycin resistance vectors. Hygromycin resistance may be used as a selectable marker in novel recombinant mycobacterial variances.