scholarly journals Secretome characterization of clinical isolates from the Mycobacterium abscessus complex provides insight into antigenic differences

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fernanda Cornejo-Granados ◽  
Thomas A. Kohl ◽  
Flor Vásquez Sotomayor ◽  
Sönke Andres ◽  
Rogelio Hernández-Pando ◽  
...  
Keyword(s):  
Drug Targets ◽  
Systematic Investigation ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Bioinformatics Pipeline ◽  
Experimental Approaches ◽  
In Silico Characterization ◽  
Insight Into

Abstract Background Mycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with the M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and 15 clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. Results We found that ~ 18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85% of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independent of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. Conclusions This study represents the first systematic prediction and in silico characterization of the MAB secretome. Our study demonstrates that bioinformatics strategies can help to broadly explore mycobacterial secretomes including those of clinical isolates and to tailor subsequent, complex and time-consuming experimental approaches accordingly. This approach can support systematic investigation exploring candidate proteins for new vaccines and diagnostic markers to distinguish between colonization and infection. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php).

scholarly journals In silico secretome characterization of clinical Mycobacterium abscessus isolates provides insights into antigenic differences

2020 ◽  
Author(s):  
Fernanda Cornejo-Granados ◽  
Thomas A. Kohl ◽  
Flor Vásquez Sotomayor ◽  
Sönke Andres ◽  
Rogelio Hernández-Pando ◽  
...  
Keyword(s):  
Drug Targets ◽  
Reference Strain ◽  
Mycobacterium Abscessus ◽  
Bioinformatics Pipeline ◽  
Diagnostic Assays ◽  
Essential Proteins ◽  
Immunogenic Proteins ◽  
Drugbank Database

AbstractMycobacterium abscessus (MAB) is a widely disseminated pathogenic non-tuberculous mycobacterium (NTM). Like with M. tuberculosis complex (MTBC), excreted / secreted (ES) proteins play an essential role for its virulence and survival inside the host. ES proteins contain highly immunogenic proteins, which are of interest for novel diagnostic assays and vaccines. Here, we used a robust bioinformatics pipeline to predict the secretome of the M. abscessus ATCC 19977 reference strain and fifteen clinical isolates belonging to all three MAB subspecies, M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. We found that ~18% of the proteins encoded in the MAB genomes were predicted as secreted and that the three MAB subspecies shared > 85 % of the predicted secretomes. MAB isolates with a rough (R) colony morphotype showed larger predicted secretomes than isolates with a smooth (S) morphotype. Additionally, proteins exclusive to the secretomes of MAB R variants had higher antigenic densities than those exclusive to S variants, independently of the subspecies. For all investigated isolates, ES proteins had a significantly higher antigenic density than non-ES proteins. We identified 337 MAB ES proteins with homologues in previously investigated M. tuberculosis secretomes. Among these, 222 have previous experimental support of secretion, and some proteins showed homology with protein drug targets reported in the DrugBank database. The predicted MAB secretomes showed a higher abundance of proteins related to quorum-sensing and Mce domains as compared to MTBC indicating the importance of these pathways for MAB pathogenicity and virulence. Comparison of the predicted secretome of M. abscessus ATCC 19977 with the list of essential genes revealed that 99 secreted proteins corresponded to essential proteins required for in vitro growth. All predicted secretomes were deposited in the Secret-AAR web-server (http://microbiomics.ibt.unam.mx/tools/aar/index.php).

IN VITRO/IN SILICO CHARACTERIZATION OF ACTIVE AND PASSIVE STRESSES IN CARDIAC MUSCLE

2012 ◽  
Vol 10 (2) ◽  
pp. 171-188 ◽  
Author(s):  
Markus Boel ◽  
Oscar J. Abilez ◽  
Ahmed N Assar ◽  
Christopher K. Zarins ◽  
Ellen Kuhl
Keyword(s):  
Cardiac Muscle ◽  
In Silico ◽  
In Silico Characterization

In-Vitro and In-Silico Characterization of Xylose Reductase from Emericella nidulans

2019 ◽  
Vol 13 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Vishal Ahuja ◽  
Aashima Sharma ◽  
Ranju Kumari Rathour ◽  
Vaishali Sharma ◽  
Nidhi Rana ◽  
...  
Keyword(s):  
Production Process ◽  
In Silico ◽  
Xylose Reductase ◽  
In Silico Analysis ◽  
Emericella Nidulans ◽  
Higher Temperature ◽  
In Silico Characterization ◽  
Silico Analysis

Background: Lignocellulosic residues generated by various anthropogenic activities can be a potential raw material for many commercial products such as biofuels, organic acids and nutraceuticals including xylitol. Xylitol is a low-calorie nutritive sweetener for diabetic patients. Microbial production of xylitol can be helpful in overcoming the drawbacks of traditional chemical production process and lowring cost of production. Objective: Designing efficient production process needs the characterization of required enzyme/s. Hence current work was focused on in-vitro and in-silico characterization of xylose reductase from Emericella nidulans. Methods: Xylose reductase from one of the hyper-producer isolates, Emericella nidulans Xlt-11 was used for in-vitro characterization. For in-silico characterization, XR sequence (Accession No: Q5BGA7) was used. Results: Xylose reductase from various microorganisms has been studied but the quest for better enzymes, their stability at higher temperature and pH still continues. Xylose reductase from Emericella nidulans Xlt-11 was found NADH dependent and utilizes xylose as its sole substrate for xylitol production. In comparison to whole cells, enzyme exhibited higher enzyme activity at lower cofactor concentration and could tolerate higher substrate concentration. Thermal deactivation profile showed that whole cell catalysts were more stable than enzyme at higher temperature. In-silico analysis of XR sequence from Emericella nidulans (Accession No: Q5BGA7) suggested that the structure was dominated by random coiling. Enzyme sequences have conserved active site with net negative charge and PI value in acidic pH range. Conclusion: Current investigation supported the enzyme’s specific application i.e. bioconversion of xylose to xylitol due to its higher selectivity. In-silico analysis may provide significant structural and physiological information for modifications and improved stability.

Systematic discovery and characterization of stress-related microRNA genes in Oryza sativa

Biologia ◽  
2015 ◽  
Vol 70 (1) ◽  
Author(s):  
Kai Bin Xie ◽  
Xue Zhou ◽  
Tian Hai Zhang ◽  
Bao Long Zhang ◽  
Li Ming Chen ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Stress Responses ◽  
Systematic Investigation ◽  
Chemical Toxicity ◽  
Promoter Regions ◽  
Crop Species ◽  
Translation Inhibition ◽  
Microrna Genes ◽  
Insight Into

AbstractAbiotic stresses including drought, salinity, extreme temperatures, chemical toxicity and oxidative are the natural status of the environment to exert serious threats to agriculture. Abiotic stress-related microRNAs (ASmiRNAs) are a group of microRNAs (miRNAs) regulating stress responses in plants. However, the systematic investigation of ASmiRNAs is limited in Rice (O. sativa), a typical abiotic stress-resistant crop species. In the present work, we systematically investigated ASmiRNAs in silico. First, we identified 177 putative ASmiRNAs in O.sativa. Second, we found most ASmiRNAs were driven by TATA-promoter and most stress-related miRNA promoter regions contained the stress-related elements. Third, we found many ASmiRNAs families were species/family specific and a set of miRNAs might derive from genomic repeat-sequences in O. sativa. Finally, we found the ASmiRNAs in O. sativa target 289 genes with 1050 predicted target sites in which 98% sites have cleavage activity and 2% sites have translation inhibition activity. In conclusion, our findings provide an insight into both the function and evolution of ASmiRNAs and improve our understanding on the mechanism of abiotic stress resistance in O. sativa.

scholarly journals Characterization of Spontaneous, In Vitro-Selected, Rifampin-Resistant Mutants of Mycobacterium tuberculosisStrain H37Rv

2000 ◽  
Vol 44 (12) ◽  
pp. 3298-3301 ◽  
Author(s):  
Glenn P. Morlock ◽  
Bonnie B. Plikaytis ◽  
Jack T. Crawford
Keyword(s):  
Point Mutations ◽  
Laboratory Strain ◽  
Resistant Mutant ◽  
Small Region ◽  
Clinical Isolates ◽  
Gene Coding ◽  
Resistant Mutants ◽  
Strain H37rv

ABSTRACT Resistance to rifampin in Mycobacterium tuberculosisresults from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions and deletions in rpoB have been identified, but point mutations in two codons, those coding for Ser531 and His526, are seen in about 70% of rifampin-resistant clinical isolates, with Ser531-to-Leu (TCG-to-TGG) mutations being by far the most common. To explore this phenomenon, we isolated independent, spontaneous, rifampin-resistant mutant versions of well-characterized M. tuberculosislaboratory strain H37Rv by plating 100 separate cultures, derived from a single low-density inoculum, onto rifampin-containing medium. Rifampin-resistant mutants were obtained from 64 of these cultures. Although we anticipated that the various point mutations would occur with approximately equal frequencies, sequencing the rpoBgene from one colony per plate revealed that 39 (60.9%) were Ser531 to Leu. We conclude that, for unknown reasons, the associated rpoB mutation occurs at a substantially higher rate than other rpoB mutations. This higher mutation rate may contribute to the high percentage of this mutation seen in clinical isolates.

scholarly journals In vitro and in silico characterization of metagenomic soil-derived cellulases capable of hydrolyzing oil palm empty fruit bunch

2017 ◽  
Vol 15 ◽  
pp. 55-62 ◽  
Author(s):  
Laura Marcela Palma Medina ◽  
Diana Catalina Ardila ◽  
María Mercedes Zambrano ◽  
Silvia Restrepo ◽  
Andrés Fernando González Barrios
Keyword(s):  
Oil Palm ◽  
In Silico ◽  
Empty Fruit Bunch ◽  
In Silico Characterization

scholarly journals In Vitro Resistance against DNA Gyrase Inhibitor SPR719 in Mycobacterium avium and Mycobacterium abscessus

2022 ◽  
Author(s):  
Wassihun Wedajo Aragaw ◽  
Nicole Cotroneo ◽  
Suzanne Stokes ◽  
Michael Pucci ◽  
Ian Critchley ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Dna Gyrase ◽  
Mycobacterium Abscessus ◽  
Drug Candidates ◽  
New Antibiotics ◽  
Novel Drug ◽  
Emergence Of Resistance

Clinical emergence of resistance to new antibiotics affects their utility. Characterization of in vitro resistance is a first step in the profiling of resistance properties of novel drug candidates.

scholarly journals A Novel Oxazolidinone, Contezolid (MRX-I), Expresses Anti-Mycobacterium abscessus Activity In Vitro

2021 ◽  
Author(s):  
Qi Guo ◽  
Liyun Xu ◽  
Fusheng Tan ◽  
Yongjie Zhang ◽  
Junsheng Fan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Novel Approach ◽  
Reference Strains

An evaluation of the anti- M. abscessus activity expressed by a novel oxazolidinone, contezolid (MRX-I), toward 12 reference strains and 194 clinical isolates was conducted. Contezolid was active against M. abscessus in vitro , and comparable to the anti- M. abscessus effects of linezolid both extracellularly and intracellularly. Contezolid did not antagonize the most frequently used anti- M. abscessus drugs nor did pre-exposure to contezolid induce drug resistance. These results provide a novel approach to treating M. abscessus infections.

Sign in / Sign up

Export Citation Format

Share Document