scholarly journals Comprehensive analysis of protein acetyltransferases of human pathogen Mycobacterium tuberculosis

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Longxiang Xie ◽  
Wenmin Yang ◽  
Xiangyu Fan ◽  
Jianping Xie

Abstract Tuberculosis (TB), a leading infectious disease caused by Mycobacterium tuberculosis strain, takes four human lives every minute globally. Paucity of knowledge on M. tuberculosis virulence and antibiotic resistance is the major challenge for tuberculosis control. We have identified 47 acetyltransferases in the M. tuberculosis, which use diverse substrates including antibiotic, amino acids, and other chemical molecules. Through comparative analysis of the protein file of the virulent M. tuberculosis H37Rv strain and the avirulent M. tuberculosis H37Ra strain, we identified one acetyltransferase that shows significant variations with N-terminal deletion, possibly influencing its physicochemical properties. We also found that one acetyltransferase has three types of post-translation modifications (lysine acetylation, succinylation, and glutarylation). The genome context analysis showed that many acetyltransferases with their neighboring genes belong to one operon. By data mining from published transcriptional profiles of M. tuberculosis exposed to diverse treatments, we revealed that several acetyltransferases may be functional during M. tuberculosis infection. Insights obtained from the present study can potentially provide clues for developing novel TB therapeutic interventions.

2018 ◽  
Vol 14 (1) ◽  
pp. 53-61
Author(s):  
Xinfeng Li ◽  
Fang Chen ◽  
Jinfeng Xiao ◽  
Shan-Ho Chou ◽  
Xuming Li ◽  
...  

Background: Riboswitches are structured elements that usually reside in the noncoding regions of mRNAs, with which various ligands bind to control a wide variety of downstream gene expressions. To date, more than twenty different classes of riboswitches have been characterized to sense various metabolites, including purines and their derivatives, coenzymes, amino acids, and metal ions, etc. </P><P> Objective: This study aims to study the genome-wide analysis of the distribution of riboswitches and function analyses of the corresponding downstream genes in prokaryotes. Results: In this study, we have completed a genome context analysis of 27 riboswitches to elucidate their metabolic capacities of riboswitch-mediated gene regulation from the completely-sequenced 3,079 prokaryotic genomes. Furthermore, Cluster of Orthologous Groups of proteins (COG) annotation was applied to predict and classify the possible functions of corresponding downstream genes of these riboswitches. We found that they could all be successfully annotated and grouped into 20 different COG functional categories, in which the two main clusters &quot;coenzyme metabolism [H]&quot; and &quot;amino acid transport and metabolism [E]&quot; were the most significantly enriched. Conclusion: Riboswitches are found to be widespread in bacteria, among which three main classes of TPP-, cobalamin- and SAM-riboswitch were the most widely distributed. We found a wide variety of functions were associated with the corresponding downstream genes, suggesting that a wide extend of regulatory roles were mediated by these riboswitches in prokaryotes.


Author(s):  
Longxiang Xie ◽  
Xiaobo Wang ◽  
Jie Zeng ◽  
Mingliang Zhou ◽  
Xiangke Duan ◽  
...  

2009 ◽  
Vol 37 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Bart de Koning ◽  
Fabian Blombach ◽  
Hao Wu ◽  
Stan J.J. Brouns ◽  
John van der Oost

MBF1 (multiprotein bridging factor 1) is a highly conserved protein in archaea and eukaryotes. It was originally identified as a mediator of the eukaryotic transcription regulator BmFTZ-F1 (Bombyx mori regulator of fushi tarazu). MBF1 was demonstrated to enhance transcription by forming a bridge between distinct regulatory DNA-binding proteins and the TATA-box-binding protein. MBF1 consists of two parts: a C-terminal part that contains a highly conserved helix–turn–helix, and an N-terminal part that shows a clear divergence: in eukaryotes, it is a weakly conserved flexible domain, whereas, in archaea, it is a conserved zinc-ribbon domain. Although its function in archaea remains elusive, its function as a transcriptional co-activator has been deduced from thorough studies of several eukaryotic proteins, often indicating a role in stress response. In addition, MBF1 was found to influence translation fidelity in yeast. Genome context analysis of mbf1 in archaea revealed conserved clustering in the crenarchaeal branch together with genes generally involved in gene expression. It points to a role of MBF1 in transcription and/or translation. Experimental data are required to allow comparison of the archaeal MBF1 with its eukaryotic counterpart.


Microbiology ◽  
2020 ◽  
Vol 166 (10) ◽  
pp. 981-987 ◽  
Author(s):  
Reyme Herman ◽  
Cavan Bennett-Ness ◽  
Abbas Maqbool ◽  
Amna Afzal ◽  
Andrew Leech ◽  
...  

The intracellular pathogen S. Typhimurium is a leading cause of foodborne illness across the world and is known to rely on a range of virulence factors to colonize the human host and cause disease. The gene coding for one such factor, stm3169, was determined to be upregulated upon macrophage entry and its disruption reduces survival in the macrophage. In this study we characterize the STM3169 protein, which forms the substrate binding protein (SBP) of an uncharacterized tripartite ATP-independent periplasmic (TRAP) transporter. Genome context analysis of the genes encoding this system in related bacteria suggests a function in sugar acid transport. We demonstrate that purified STM3169 binds d-glucuronic acid with high affinity and specificity. S. Typhimurium LT2 can use this sugar acid as a sole carbon source and the genes for a probable catabolic pathway are present in the genome. As this gene was previously implicated in macrophage survival, it suggests a role for d-glucuronate as an important carbon source for S. Typhimurium in this environment.


2003 ◽  
Vol 185 (5) ◽  
pp. 1745-1748 ◽  
Author(s):  
Jan Rybniker ◽  
Martina Wolke ◽  
Christiane Haefs ◽  
Georg Plum

ABSTRACT Mycobacterium marinum is a close relative of the obligate human pathogen Mycobacterium tuberculosis. As with M. tuberculosis, M. marinum causes intracellular infection of poikilothermic vertebrates and skin infection in humans. It is considered a valid model organism for the study of intracellular pathogenesis of mycobacteria. Low transformation efficiencies for this species have precluded approaches using mutant libraries in pathogenesis studies. We have adapted the conditionally replicating mycobacteriophage phAE94, originally developed as a transposon mutagenesis tool for M. tuberculosis, to meet the specific requirements of M. marinum. Conditions permissive for phage replication in M. tuberculosis facilitated highly efficient transposon delivery in M. marinum. Using this technique we succeeded in generating a representative mutant library of this species, and we conclude that TM4-derived mycobacteriophages are temperature-independent suicide vectors for M. marinum.


Microbiology ◽  
2014 ◽  
Vol 160 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
Viveshree S. Govender ◽  
Saiyur Ramsugit ◽  
Manormoney Pillay

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.


2008 ◽  
Vol 34 (12) ◽  
pp. 1063-1068 ◽  
Author(s):  
Joycenea Matsuda Mendes ◽  
Silvia Maria Almeida Machado ◽  
Maria Cristina Lourenço ◽  
Rosa Maria Carvalho Ferreira ◽  
Leila de Souza Fonseca ◽  
...  

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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