Systematic, multiparametric analysis of Mycobacterium tuberculosis intracellular infection offers insight into coordinated virulence

Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host’s defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host–pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

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Molecular diversity of Mycobacterium tuberculosis strains in a slum area of Rio de Janeiro, Brazil

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132008001200012 ◽

2008 ◽

Vol 34 (12) ◽

pp. 1063-1068 ◽

Cited By ~ 3

Author(s):

Joycenea Matsuda Mendes ◽

Silvia Maria Almeida Machado ◽

Maria Cristina Lourenço ◽

Rosa Maria Carvalho Ferreira ◽

Leila de Souza Fonseca ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Rio De Janeiro ◽

Insertion Sequence ◽

Fragment Length Polymorphism ◽

Control Program ◽

Molecular Study ◽

Tuberculosis Control ◽

Primary Resistance ◽

The City ◽

Insight Into

This retrospective molecular study involving restriction fragment length polymorphism, using insertion sequence 6110 as a marker, was conducted in order to provide an initial insight into the genetic diversity of Mycobacterium tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3%) were found to belong to clusters (total clusters, 10). Household and social chains of transmission were associated with clustering, in 20% and 60%, respectively. Living in the Conjunto Habitacional Programado 2 slum was associated with clustering. Although not significant, it is relevant that 26% of the clustered strains presented primary resistance. These findings, although possibly underestimating the prevalence due to the failure to analyze all strains, could help improve the local tuberculosis control program.

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Functional Analysis of the Mycobacterium tuberculosis FAD-Dependent Thymidylate Synthase, ThyX, Reveals New Amino Acid Residues Contributing to an Extended ThyX Motif

Journal of Bacteriology ◽

10.1128/jb.01094-07 ◽

2008 ◽

Vol 190 (6) ◽

pp. 2056-2064 ◽

Cited By ~ 17

Author(s):

Jonathan E. Ulmer ◽

Yap Boum ◽

Christopher D. Thouvenel ◽

Hannu Myllykallio ◽

Carol Hopkins Sibley

Keyword(s):

Mycobacterium Tuberculosis ◽

Thymidylate Synthase ◽

Three Dimensional ◽

Pyrimidine Ring ◽

Dimensional Structure ◽

Directed Mutagenesis ◽

Catalytic Residue ◽

Amino Acid Residues ◽

Insight Into

ABSTRACT A novel FAD-dependent thymidylate synthase, ThyX, is present in a variety of eubacteria and archaea, including the mycobacteria. A short motif found in all thyX genes, RHRX7-8S, has been identified. The three-dimensional structure of the Mycobacterium tuberculosis ThyX enzyme has been solved. Building upon this information, we used directed mutagenesis to produce 67 mutants of the M. tuberculosis thyX gene. Each enzyme was assayed to determine its ability to complement the defect in thymidine biosynthesis in a ΔthyA strain of Escherichia coli. Enzymes from selected strains were then tested in vitro for their ability to catalyze the oxidation of NADPH and the release of a proton from position 5 of the pyrimidine ring of dUMP. The results defined an extended motif of amino acids essential to enzyme activity in M. tuberculosis (Y44X24 H69X25R95HRX7 S105XRYX90R199 [with the underlined histidine acting as the catalytic residue and the underlined serine as the nucleophile]) and provided insight into the ThyX reaction mechanism. ThyX is found in a variety of bacterial pathogens but is absent in humans, which depend upon an unrelated thymidylate synthase, ThyA. Therefore, ThyX is a potential target for development of antibacterial drugs.

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Mincle is a long sought receptor for mycobacterial cord factor

Journal of Experimental Medicine ◽

10.1084/jem.20092533 ◽

2009 ◽

Vol 206 (13) ◽

pp. 2865-2868 ◽

Cited By ~ 62

Author(s):

Isamu Matsunaga ◽

D. Branch Moody

Keyword(s):

Cell Wall ◽

Mycobacterium Tuberculosis ◽

Research Effort ◽

Therapeutic Tool ◽

Cord Factor ◽

Insight Into

Mycobacterium tuberculosis is a leading killer worldwide, yet the adjuvancy of its cell wall has proven to be a valuable therapeutic tool for vaccination and immunotherapy. Much research effort has focused on the mycobacterial glycolipid trehalose-6,6’-dimycolate (TDM), a potent immunostimulant that is also known as cord factor. Now, the identification of the monocyte-inducible C-type lectin (Mincle) as an essential receptor for TDM provides new insight into the formation of the characteristic granulomas in tuberculosis and an avenue for rational adjuvant design.

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Structural insight into conformational dynamics of non-active site mutations in KasA: A Mycobacterium tuberculosis target protein

Gene ◽

10.1016/j.gene.2019.144082 ◽

2019 ◽

Vol 720 ◽

pp. 144082 ◽

Cited By ~ 2

Author(s):

Manikandan Jayaraman ◽

Savita Kumari Rajendra ◽

Krishna Ramadas

Keyword(s):

Mycobacterium Tuberculosis ◽

Active Site ◽

Conformational Dynamics ◽

Target Protein ◽

Structural Insight ◽

Insight Into ◽

Active Site Mutations

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The gene expression data of Mycobacterium tuberculosis based on Affymetrix gene chips provide insight into regulatory and hypothetical genes

BMC Microbiology ◽

10.1186/1471-2180-7-37 ◽

2007 ◽

Vol 7 (1) ◽

pp. 37 ◽

Cited By ~ 15

Author(s):

Li M Fu ◽

Casey S Fu-Liu

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Gene Expression Data ◽

Expression Data ◽

Gene Chips ◽

Hypothetical Genes ◽

Insight Into

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Identification and Characterization of Mycobacterium tuberculosis Beijing Genotype Strain SBH163, Isolated in Sabah, Malaysia

Microbiology Resource Announcements ◽

10.1128/mra.01322-19 ◽

2020 ◽

Vol 9 (2) ◽

Author(s):

Jaeyres Jani ◽

Siti Fatimah Abu Bakar ◽

Zainal Arifin Mustapha ◽

Chin Kai Ling ◽

Roddy Teo ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequence ◽

Beijing Genotype ◽

Molecular Characteristics ◽

Whole Genome ◽

Content Type ◽

Identification And Characterization ◽

Insight Into ◽

Malaysian Borneo

This is a report on the whole-genome sequence of Mycobacterium tuberculosis strain SBH163, which was isolated from a patient in the Malaysian Borneo state of Sabah. This report provides insight into the molecular characteristics of an M. tuberculosis Beijing genotype strain related to strains from Russia and South Africa.

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