Literature Search. A literature search was conducted of all publications evaluating molecules associated with drug resistance in Mycobacteria. The search was restricted to studies published from 1959 through October 1, 2018, including those studies available online prior to publication. Totally 32 keywords were used to search the Pubmed database.
Study Selection Criteria. Studies were included if they met the following predetermined criteria: 1) published in English, 2) presented original data, and 3) assessed drug resistance based on phenotypic and genotypic drug susceptible test method. Both molecular epidemiology and mechanism exploration research were reviewed in this work.
To systematically achieve high quality information of drug resistance-associated molecules in Mycobacteria, we searched the PubMed database with a list of keywords, and reviewed more than 3,705 published literatures in detail. As a result, a total of 1,707 curated associations between 73 compounds and 132 molecules in 6 species (including M. tuberculosis, M. smegmatis, M. bovis, M. marinum, M. leprae, and M. abscessus) were manually collected from 1,277 studies. Especially, we also gathered comprehensive information of epidemiology summary and molecule change for clinical MDR and XDR isolates. Furthermore, we obtained additional descriptions of compounds and molecules (such as basic information of compounds, genomic annotation of molecules and so on), and provided useful links to other databases, including com-pounds in the PubChem databases, and molecules in Mycobrowser databases.
In our resource, all collected records could be divided into two parts: ‘Molecular Epidemiology’ section and ‘Mechanism Exploration’ section. The ‘Molecular Epidemiology’ section was mainly focused on studies that characterized the diversity and frequency of mutation in resistant and susceptible Mycobacteria strains. In this section, we not only obtained detailed genome variation data (including mutation position, nucleotide or amino acid change, mutation category and mutation frequency) for clinical isolates with phenotypic resistance profiles, but also extracted the epidemiological information of these clinical isolates, including Tuberculosis category, geographic origin, lineage distribution and drug resistance pattern. On the other hand, the research that uncovered the potential roles of molecules in drug resistance were compiled in the ‘Mechanism Exploration’ section. Each ‘Mechanism Exploration’ record summarized the effect of molecule on drug resistance, and provided key details of experiment, such as research strategy, experimental model and drug susceptibility testing.
The MycoResistance furnishes a user-friendly web interface that enables users to browse, search and retrieve the records of drug resistance-molecule associations in Mycobacteria. On the ‘Browse’ page, users can scan all compounds in the database by clicking a specific compound name, and review a full report of curated molecules that were associated with drug resistance. Additionally, four kinds of query option, including ‘Species’, ‘Compound’, ‘Molecule’ and ‘Research Category’, are allowed on the ‘Search’ page. Especially, our re-source also provides direct links to the overview of MDR and XDR research. Furthermore, through separate or composite querying, users can get access to ‘Molecular Epidemiology’ and ‘Mechanism Exploration’ records on the ‘Result’ page. Finally, all data in the database can be obtained on the ‘Download’ page, and a detailed tutorial showing users how to use MycoResistance is available on the ‘Manual’ page.
Literature Summary Record Summarys Research Category Reference Support
Epidemiology Summary Patient Summary: Tuberculosis Category and Geographic Origin Drug Resistance Pattern Lineage Distribution Detection Method: Phenotypic and Genotypic Drug Susceptibility Test
Molecular Change Details Molecule Changes Change Type Change Region Resistant MutFreq Susceptible MutFreq
Mechanism Summary Effect Strategy Model: In Vitro and In Vivo Model Detection Method: Phenotypic and Genotypic Drug Susceptibility Test Evidence
Literature Summary Research Category Reference Support
Multidrug-resistant Tuberculosis (MDR-TB): Resistance to rifampicin and isoniazid.
Extensively drug-resistant Tuberculosis (XDR-TB): Resistance to rifampicin and isoniazid, and further resistance to the fluoroquinolones and any of the injectable drugs (amikacin, kanamycin or capreomycin).
Resistant MutFreq: Number of resistant isolates with mutation / Total number of resistant isolates
Susceptible MutFreq: Number of susceptible isolates with mutation / Total number of susceptible isolates