Efforts on identifying new antibiotics were once a top research and development priority among pharmaceutical companies. However, the treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutation or acquisition of resistance genes. Treatment failure can have serious consequences in patients with infections of some pathogens, such as methicillin-resistant Staphyococcus aureus or vancomycin-resistant Enterococcus. Antibiotic resistance genes are also potentially be used by bio-terrorists in genetically modified organisms. In order to facilitate identification and characterization of antibiotic resistance genes, we have created a manually curated database (ARDB) unifying most of the publicly available resistance genes and related information. Resistance genes are further categorized to resistance types by their resistance profiles and sequence similarity. Each gene or type is annotated with rich information, including resistance profile, resistance mechanism, resistance requirement, epidemiology, GO term, COG and CDD. ARDB allows the user to browse and search antibiotic resistance information from a view of gene, type, organism and antibiotic. Regular BLAST and RPS-BLAST tools would help the user to identify and annotate new potential resistance genes by blasting against ARDB DNA or protein sequences. ARDB can help user to identify mutational resistance for 12 antibiotic target genes by BLAST. Currently, ARDB contains resistance information for 13293 genes, 377 types, 257 antibiotics, 3369 species and 124 genera.
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- Resistance Type
- Antibiotic resistance genes can be grouped by their resistance type. Genes belonging to the same
resistance type confer same resistance profile and have same action mechanism. This database contains information, such as resistance profile, mechanism, requirement, epidemiology for each type.
- Resistance Gene
- Resistance gene can confer antibiotic resistance to one or several antibiotics, by inactivation,
protection, substitution, efflux pumping, etc. This database contains information, such as resistance profile, resistance type, requirement, protein and DNA sequence for each gene.This database only includes NON-REDUNDANT, NON-VECTOR, COMPLETE genes.
- Antibiotic
- Antibiotic can inhibit bacteria growth or kill them, by inhibiting cell wall synthesis, protein synthesis, DNA synthesis and transcription, etc. This database contains information, such as producer, action mechanism, resistance type, for each gene.
- Resistance Gene(NonRD)
- This database contains the same information as Resistance Gene. It does NOT include NON-REDUNDANT, NON-VECTOR genes, but includes INCOMPLETE genes.
- Resistance Gene(ALL)
- This database contains the same information as Resistance Gene. It includes all REDUNDANT, VECTOR AND INCOMPLETE genes.
- Resistance Species
- This database contains resistance profile and corresponding resistance genes for each species.
- Resistance Genus
- This database contains resistance types information for each genus.
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- Resistance Genes Complete
- Contains only NON-REDUNDANT, NON-VECTOR, COMPLETE genes sequences.
- Resistance Genes Non-redundant
- Contains NON-REDUNDANT, NON-VECTOR, COMPLETE, INCOMPLETE genes sequences.
- Resistance Genes All
- Contains all REDUNDANT, VECTOR, COMPLETE, INCOMPLETE genes sequences.
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Aquired resistance genes (horizontal gene transfer) among bacterial strains or species are often considered to be the main mediator of
antibiotic resistance. However mutational resistance is another important way to confer resistance to particular antibiotics
(fluoroquinolones and oxazolidinones), especially in certain species, such as Mycobacterium tuberculosis and
Helicobacter pylori.
- 16S rRNA
- Both of aminoglycosides and tetracyclines can prevent the attachment of aminoacyl-tRNA to the ribosomal
acceptor (A) site by interaction with 16s rRNA. Hence they can inhibit protein synthesis.
Mutation in some bases of 16s rRNA causes antibiotic can not interfere with it anymore to confer antibiotic resistance.
- 23S rRNA
- Macrolides, licosamide, streptogramin_B (MLS) antibiotics inhibit protein biosynthesis by targeting the peptidyl transferase
centre within the 50S ribosomal subunit (23S rRNA). Mutation in 23S rRNA causes these antibiotic can not interfere with
it anymore.
- gyrA
- DNA gyrase (type II topoisomerases) is a tetrameric enzyme composed of two A subunits and two B subunits,
encoded by gyrA and gyrB. The main function of this enzyme is to catalyse the
negative supercoiling of DNA. Quinolone antibiotics can bind to the gyrA inhibiting DNA transcription. Mutation in
some regions of gyrA can protect the gyrA gene from the inhibition of quinolone.
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Database
For information about different databases, click here
- All Field
- If you have no idea where your search keyword would appear, then use this default (All Field) search field.
This may take longer time than if you specified the search field
- Antibiotic
- If you are interested in a specific antibiotic, such as tetracycline. Then you can choose this field.
- Species
- If you are interested in a species, such as Escherichia coli. Then you can choose this field. You can
also use the corresponding NCBI taxon ID instead of the organism name as the search word.
Sorry that it does not support short names, such as E.coli.
- Genus
- If you are interested in a specific genus, such as Staphylococcus. Then you can choose this field. You can
also use the corresponding NCBI taxon ID instead of the organism name as the search word.
- Gene Name
- If you are interested in a specific resistance gene, such as tetM or tetO (ribosomal protection protein).
Then you can choose this field.
- NCBI ID
- If you are interested in a specific sequence record (both DNA or protein) in NCBI, such as ABI95378. Then you can choose this field.
However the database is not updated very frequently, so some newly created resistance gene sequences in NCBI are not included.
Then you can choose the BLAST function to identify this gene.
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- Normal BLAST
- This function allows an user to input a DNA or protein sequence, and find similar DNA (Nucleotide BLAST) or protein (Protein BLAST) sequences using blastn, blastp, blastx, tblastn, tblastx
- RPS BLAST
- A web RPSBLAST (RPS BLAST) interface is provided to align a query sequence against the
Position Specific Scoring Matrix (PSSM) for each type. Normally, this will give the same annotation information as using regular
BLAST mentioned above.
- Multiple Sequences BLAST (Genome Annotation)
- This function (Genome Annotation) allows an user to annotate multiple (less than 5000) query sequences in FASTA format.
For example, this function can be used to annotate a bacterial genome or large transposon.
- Mutation Resistance Identification
- This function (Mutation Resistance Identification) allows an user to identify mutations that will cause potential antibiotic resistance, for 12 genes
(16S rRNA, 23S rRNA, gyrA, gyrB, parC, parE, rpoB, katG, pncA, embB, folP, dfr)
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Similarity: 99.82 % Cutoff: 85% Query Length: 568 Hit Length: 639 No. of Identicals: 567 HSP Length: 568
ID PROTEIN:ZP_00603114 DNA:NZ_AAAK03000007 NON-REDUNDANT COMPLETE
TYPE tetm
DEFINITION Ribosomal protection protein, which protects ribosome from the translation inhibition of tetracycline.
RESISTANCE tetracycline
ORGANISM Enterococcus faecium DO
COG COG480 Translation elongation factors (GTPases)[Translation, ribosomal structure and biogenesis];
CDD 58081: Tet_II 58278: Tet_like_IV 58051: TetM_like 58064: Tet_C 30828: FusA
GO 0003746
PROTEIN MKIINIGVLAHVDAGKTTLTESLLYNSGAITELGSVDKGTTRTDNTLLERQRGITIQTGITSFQWENTKVNIIDT
PGHMDFLAEVYRSLSVLDGAILLISAKDGVQAQTRILFHALRKMGIPTIFFINKIDQNGIDLSTVYQDIKEKLSM
EIIIKQKVELHPNMCVMSCTEPEQWDVVIEGNDDLLEKYMSGKSLEALELEQEEIRRFQNCSLYPVYHGSAKSNI
GIEQLIEVITNKFYSSTYRKKSELCGNVFKIEYSEERQRLAYVRLYGGILHLRDSVRISEKEKIKITEMYTSING
ELCKIDKAYSGEIVILQNEFLKLNSVLGDTKLLPQRERIENPLPLLQTTVEPSKPQQREMLLDALLEISDSDPLL
QYYVDSTTHEIILSFLGKVQMEVISALLQEKYHVEIELKEPTVIYMERPLKNAEYTIHIEVPPNPFWASIGLSVS
PLPLGSGMQYESSVSLGYLNQSFQNAVMEGIRYGCEQGLYGWNVTDCKICFKYGLYYSPVSTPADFRMLAPIVLE
QVLKKAGTELLEPYLSFKIYAPQEYLSRAYNDAPKYCANIVDTQLKNNEVILSGEIPARCIQEYRSDLTFFTNGR
SVCLTELKGYHVTTGEPVCQPRRPNSRIDKVRYMFNKIT
DNA ATGAAAATTATTAATATTGGAGTTTTAGCTCATGTTGATGCAGGAAAAACTACCTTAACAGAAAGCTTATTATAT
AACAGTGGAGCGATTACAGAATTAGGAAGCGTGGACAAAGGTACAACGAGGACGGATAATACGCTTTTAGAACGT
CAGAGAGGAATTACAATTCAGACAGGAATAACCTCTTTTCAGTGGGAAAATACGAAGGTGAACATCATAGACACG
CCAGGACATATGGATTTCTTAGCAGAAGTATATCGTTCATTATCAGTTTTAGATGGGGCAATTCTACTGATTTCT
GCAAAAGATGGCGTACAAGCACAAACTCGTATATTATTTCATGCACTTAGGAAAATGGGGATTCCCACAATCTTT
TTTATCAATAAGATTGACCAAAATGGAATTGATTTATCAACGGTTTATCAGGATATTAAAGAGAAACTTTCTATG
GAAATTATAATCAAACAGAAAGTAGAGCTGCACCCTAATATGTGTGTGATGAGCTGTACGGAACCTGAGCAATGG
GATGTGGTAATAGAAGGAAATGATGACCTTTTAGAGAAATATATGTCCGGTAAATCATTAGAAGCATTAGAACTC
GAACAAGAGGAAATCAGAAGATTTCAGAATTGCTCCTTGTACCCTGTTTATCATGGAAGCGCAAAAAGCAACATA
GGGATTGAGCAGCTTATAGAAGTGATAACGAATAAATTTTATTCATCAACATACAGAAAGAAGTCTGAACTTTGC
GGAAATGTCTTCAAAATTGAATATTCGGAAGAAAGACAACGTCTTGCATATGTACGCCTTTATGGCGGAATCCTG
CATTTGCGGGATTCGGTTAGAATATCGGAAAAGGAAAAAATAAAAATTACAGAAATGTATACTTCAATAAATGGT
GAATTATGTAAAATTGATAAGGCTTATTCCGGGGAAATTGTTATTTTGCAAAATGAGTTTTTGAAGCTAAATAGT
GTTCTTGGAGATACAAAGCTATTGCCACAGAGAGAGAGAATTGAAAATCCGCTCCCTCTGCTGCAAACAACTGTT
GAACCGAGCAAACCTCAACAAAGGGAAATGTTACTTGATGCACTTTTAGAAATCTCCGACAGTGACCCGCTTCTA
CAATATTATGTGGATTCTACGACACATGAAATTATACTTTCTTTCTTAGGGAAAGTACAAATGGAAGTGATTAGT
GCACTGTTGCAAGAAAAGTATCATGTGGAGATAGAACTAAAAGAGCCTACAGTCATTTATATGGAGAGACCGTTA
AAAAATGCAGAATATACCATTCACATCGAAGTGCCGCCAAATCCTTTCTGGGCTTCCATTGGTTTATCTGTATCA
CCGCTTCCGTTGGGAAGTGGAATGCAGTATGAGAGCTCGGTTTCTCTTGGATACTTAAATCAATCATTTCAAAAT
GCAGTTATGGAAGGGATACGCTATGGTTGCGAACAAGGATTATATGGTTGGAATGTGACGGATTGTAAAATCTGT
TTTAAGTATGGCTTATACTATAGCCCTGTTAGTACCCCAGCAGATTTTCGGATGCTTGCTCCTATTGTATTGGAA
CAAGTCTTAAAAAAAGCTGGAACAGAATTGTTAGAGCCATATCTTAGTTTTAAAATTTATGCGCCACAGGAATAT
CTTTCACGAGCATACAACGATGCTCCTAAATATTGTGCGAACATCGTAGACACTCAATTGAAAAATAATGAGGTC
ATTCTTAGTGGAGAAATCCCTGCTCGGTGTATTCAAGAATATCGTAGTGATTTAACTTTCTTTACAAATGGACGT
AGTGTTTGTTTAACAGAGTTAAAAGGGTACCATGTTACTACCGGTGAACCTGTTTGCCAGCCCCGTCGTCCAAAT
AGTCGGATAGATAAAGTACGATATATGTTCAATAAAATAACTTAG
- Similarity
- Percent Identity between the query sequence and ARDB sequence. This value is extracted from the BLAST results.
- Cutoff
- Actually this cutoff value is arbitrarily chosen from the original published papers, because there is no experimental
evidence that sequences beyond this cutoff do not belong this resistance type or do not have antibiotic resistance function.
This cutoff value is just to say that, right now, sequences belonging this resistance type are within this percent identity cutoff.
- Query Length
- The lenght of your query sequence.
- Hit Length
- The length of the hit sequence in ARDB database.
- No. of Identicals
- Number of identical bases between query sequence and hit sequence in ARDB database.
- HSP Length
- The length of the High Scoring Pair (HSP) formed between query sequence and hit sequence in ARDB database.
- Protein ID
- This is the GenBank ID for the protein sequence of this gene.
- DNA ID
- This is the GenBank ID for the DNA sequence of this gene. Since there is not always a specific nucleotide sequence record for each gene,
this dna sequence may be contained in another large chunk of DNA, such a genome.
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