ARDB-Antibiotic Resistance Genes Database

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Introduction

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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Databases

Resistance Genes Search Database

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.

Resistance Genes BLAST Database

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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Mutational Resistance Identification

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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Search

Database

For information about different databases, click here

Search Field

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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Analysis & Tools

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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Output Format

BLAST Annotation Format

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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