INCFinder

GenBank ID	PV023017.1
Plasmid name	p04A19003_A_NDM
Classification	C1/2 hybrid
Length	178 145 bp
GC content	53%
Organism	Citrobacter freundii strain 04A19CPO003
Curation	Manually annotated

Plasmid map

Notes

The empty site of I2 insertion is intact. The presence of the Type1-specific alleles orf1832 and RHS1 and the Type2-specific insertion I1 suggests that this is an IncC1/C2 hybrid plasmid.

Characteristic genes

Gene name	Length	Location	Length of alignment	Identity (%)	Coverage (%)
repA	1101	1 - 1101 (+)	1101	100	100
ORF1832	5499	102525 - 108023 (-)	5499	100	100
I1	428	20829 - 21256 (+)	428	100	100
RHS1	4254	151904 - 156157 (+)	4254	100	100
AriB	1558	134804 - 136361 (-)	1558	100	59
AriB	429	134383 - 134811 (-)	429	100	16

Antimicrobial resistance genes

Type match	Model name	Model type	Location	E-value	Identity
Strict	dfrA14	protein homolog model	32094 - 32567(+)	2.51244e-118	98.73 %
trimethoprim resistant dihydrofolate reductase dfr AMR Gene Family Alternative dihydropteroate synthase dfr present on plasmids produces alternate proteins that are less sensitive to trimethoprim from inhibiting its role in folate synthesis, thus conferring trimethoprim resistance. trimethoprim Antibiotic Trimethoprim is a synthetic 5-(3,4,5- trimethoxybenzyl) pyrimidine inhibitor of dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the de novo synthesis of the DNA nucleotide thymidine. Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections in combination with sulfamethoxazole, a sulfonamide antibiotic. diaminopyrimidine antibiotic Drug Class Diaminopyrimidines are a class of organic compounds containing a pyrimidine ring substituted by two amine groups. They are inhibitors of dihydrofolate reductase, an enzyme critical for DNA synthesis. antibiotic target replacement Resistance Mechanism Replacement or substitution of antibiotic action target, which process will result in antibiotic resistance.
Perfect	arr-2	protein homolog model	32678 - 33130(+)	2.33764e-112	100 %
rifampin ADP-ribosyltransferase (Arr) AMR Gene Family Enzyme responsible for the ADP-ribosylative inactivation of rifampin at the 23-OH position using NAD+. rifampin Antibiotic Rifampin is a semi-synthetic rifamycin, and inhibits RNA synthesis by binding to RNA polymerase. Rifampin is the mainstay agent for the treatment of tuberculosis, leprosy and complicated Gram-positive infections. rifaximin Antibiotic Rifaximin is a semi-synthetic rifamycin used to treat traveller's diarrhea. Rifaximin inhibits RNA synthesis by binding to the beta subunit of bacterial RNA polymerase. rifabutin Antibiotic Rifabutin is a semisynthetic rifamycin used in tuberculosis therapy. It inhibits DNA-dependent RNA synthesis. rifapentine Antibiotic Rifapentine is a semisynthetic rifamycin that inhibits DNA-dependent RNA synthesis. It is often used in the treatment of tuberculosis and leprosy. rifamycin antibiotic Drug Class Rifamycin antibiotics are a group of broad-spectrum ansamycin antibiotics that inhibit bacterial RNA polymerase by binding to a highly conserved region, blocking the oligonucleotide exit tunnel, and preventing the extension of nascent mRNAs. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.
Perfect	cmlA5	protein homolog model	33451 - 34710(+)	0	100 %
major facilitator superfamily (MFS) antibiotic efflux pump AMR Gene Family Directed pumping of antibiotic out of a cell to confer resistance. Major facilitator superfamily (MFS) transporters and ABC transporters comprise the two largest and most functionally diverse of the transporter superfamilies. However, MFS transporters are distinct from ABC transporters in both their primary sequence and structure and in the mechanism of energy coupling. As secondary transporters they are, like RND and SMR transporters, energized by the electrochemical proton gradient. chloramphenicol Antibiotic Chloramphenicol is a bacteriostatic antimicrobial originally derived from the bacterium Streptomyces venezuelae. It was the first antibiotic to be manufactured synthetically on a large scale. It functions by inhibiting peptidyl transferase activity of the bacterial ribosome, binding to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit and preventing peptide bond formation. phenicol antibiotic Drug Class Phenicols are broad spectrum bacteriostatic antibiotics acting on bacterial protein synthesis. More specifically, the phenicols block peptide elongation by binding to the peptidyltansferase centre of the 70S ribosome. efflux pump complex or subunit conferring antibiotic resistance Efflux Component Efflux proteins that pump antibiotic out of a cell to confer resistance. antibiotic efflux Resistance Mechanism Antibiotic resistance via the transport of antibiotics out of the cell.
Perfect	OXA-10	protein homolog model	34975 - 35775(+)	0	100 %
OXA beta-lactamase AMR Gene Family OXA beta-lactamases were long recognized as a less common but also plasmid-mediated beta-lactamase variety that could hydrolyze oxacillin and related anti-staphylococcal penicillins. These beta-lactamases differ from the TEM and SHV enzymes in that they belong to molecular class D and functional group 2d. The OXA-type beta-lactamases confer resistance to ampicillin and cephalothin and are characterized by their high hydrolytic activity against oxacillin and cloxacillin and the fact that they are poorly inhibited by clavulanic acid. Amino acid substitutions in OXA enzymes can also give the ESBL phenotype. The OXA beta-lactamase family was originally created as a phenotypic rather than a genotypic group for a few beta-lactamases that had a specific hydrolysis profile. Therefore, there is as little as 20% sequence homology among some of the members of this family. However, recent additions to this family show some degree of homology to one or more of the existing members of the OXA beta-lactamase family. Some confer resistance predominantly to ceftazidime, but OXA-17 confers greater resistance to cefotaxime and cefepime than it does resistance to ceftazidime. cephalosporin Drug Class Cephalosporins are a class of beta-lactam antibiotics, containing the beta-lactam ring fused with a dihydrothiazolidine ring. Together with cephamycins they belong to a sub-group called cephems. Cephalosporin are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. penam Drug Class Penams, often referred to as penicillins, are a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections. Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are beta-lactam antibiotics in the penam sub-group, and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.
Strict	ANT(3'')-IIa	protein homolog model	35768 - 36583(+)	0	99.63 %
ANT(3'') AMR Gene Family Nucleotidylylation of streptomycin at the hydroxyl group at position 3'' aminoglycoside antibiotic Drug Class Aminoglycosides are a group of antibiotics that are mostly effective against Gram-negative bacteria. These molecules consist of aminated sugars attached to a dibasic cyclitol. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.
Perfect	sul1	protein homolog model	37088 - 37927(+)	0	100 %
sulfonamide resistant sul AMR Gene Family The sul genes encode forms of dihydropteroate synthase that confer resistance to sulfonamide. sulfadiazine Antibiotic Sulfadiazine is a potent inhibitor of dihydropteroate synthase, interfering with the tetrahydrofolic biosynthesis pathway. Tetrahydrofolic acid is essential for folate synthesis, a precursor to many nucleotides and amino acids. sulfadimidine Antibiotic Sulfadimidine is an alkaline sulfonamide antibiotic that inhibits dihydropteroate synthase, and enzyme in the tetrahydrofolic acid biosynthesis pathway. This interferes with the production of folate, which is a precursor to many amino acids and nucleotides. sulfadoxine Antibiotic Sulfadoxine is an inhibitor of dihydropteroate synthase, interfering with the tetrahydrofolic biosynthesis pathway. Tetrahydrofolic acid is essential for folate synthesis, a precursor to many nucleotides and amino acids. sulfamethoxazole Antibiotic Sulfamethoxazole is a sulfonamide antibiotic usually taken with trimethoprim, a diaminopyrimidine antibiotic. Sulfamethoxazole inhibits dihydropteroate synthase, essential to tetrahydrofolic acid biosynthesis. This pathway generates compounds used in the synthesis of many amino acids and nucleotides. sulfisoxazole Antibiotic Sulfisoxazole is an inhibitor of dihydropteroate synthase, interfering with the tetrahydrofolic biosynthesis pathway. Tetrahydrofolic acid is essential for folate synthesis, a precursor to many nucleotides and amino acids. sulfacetamide Antibiotic Sulfacetamide is a very soluable sulfonamide antibiotic previously used to treat urinary tract infections. Its relatively low activity and toxicity to those with Stevens-Johnson syndrome have reduced its use and availability. mafenide Antibiotic Mafenide is a sulfonamide used topically for treating burns. sulfasalazine Antibiotic Sulfasalazine is a derivative of the early sulfonamide sulfapyridine (salicylazosulfapyridine). It was developed to increase water solubility and is taken orally for ulcerative colitis. sulfamethizole Antibiotic Sulfamethizole is a short-acting sulfonamide that inhibits dihydropteroate synthetase. sulfonamide antibiotic Drug Class Sulfonamides are broad spectrum, synthetic antibiotics that contain the sulfonamide group. Sulfonamides inhibit dihydropteroate synthase, which catalyzes the conversion of p-aminobenzoic acid to dihydropteroic acid as part of the tetrahydrofolic acid biosynthetic pathway. Tetrahydrofolic acid is essential for folate synthesis, a precursor of many nucleotides and amino acids. Many sulfamides are taken with trimethoprim, an inhibitor of dihydrofolate reductase, also disturbing the trihydrofolic acid synthesis pathway. antibiotic target replacement Resistance Mechanism Replacement or substitution of antibiotic action target, which process will result in antibiotic resistance.
Perfect	determinant of bleomycin resistance	protein homolog model	46018 - 46383(-)	3.54274e-89	100 %
Bleomycin resistant protein AMR Gene Family Bleomycin resistant proteins (BRP) confer resistance to bleomycin and to bleomycin-like molecules. bleomycinic acid Antibiotic Bleomycinic acid is a glycopeptide antibiotic produced by Streptomyces verticillus taken as a mixture of bleomycins. It induces stand breaks in bacterial nucleic acids. bleomycin A2 Antibiotic Bleomycin A2 is a glycopeptide antibiotic produced by Streptomyces verticillus taken as a mixture of bleomycins. It induces stand breaks in bacterial nucleic acids. bleomycin B2 Antibiotic Bleomycin B2 is a glycopeptide antibiotic produced by Streptomyces verticillus taken as a mixture of bleomycins. It induces stand breaks in bacterial nucleic acids. glycopeptide antibiotic Drug Class Glycopeptide antibiotics are natural products produced non-ribosomally by Actinomycetales bacteria. With the exception of bleomycins, they act by binding the terminal D-Ala-D-Ala in peptidoglycan precursors of the growing bacterial cell wall and are generally active against Gram-positive bacteria. This inhibits transglycosylation leading to cell death due to osmotic stress. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.
Perfect	NDM-1	protein homolog model	46387 - 47199(-)	0	100 %
clavulanic acid Adjuvant Clavulanic acid is a beta-lactamase inhibitor (marketed by GlaxoSmithKline, formerly Beecham) combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. It is used to overcome resistance in bacteria that secrete beta-lactamase, which otherwise inactivates most penicillins. NDM beta-lactamase AMR Gene Family NDM beta-lactamases or New Delhi metallo-beta-lactamases are class B beta-lactamases that confer resistance to a broad range of antibiotics including carbapenems, cephalosporins and penicillins. amoxicillin Antibiotic Amoxicillin is a moderate-spectrum, bacteriolytic, beta-lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. A derivative of penicillin, it has a wider range of treatment but remains relatively ineffective against Gram-negative bacteria. It is commonly taken with clavulanic acid, a beta-lactamase inhibitor. Like other beta-lactams, amoxicillin interferes with the synthesis of peptidoglycan. ertapenem Antibiotic Ertapenem is a carbapenem antibiotic and is highly resistant to beta-lactamases like other carbapenems. It inhibits bacterial cell wall synthesis. meropenem Antibiotic Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. imipenem Antibiotic Imipenem is a broad-spectrum antibiotic and is usually taken with cilastatin, which prevents hydrolysis of imipenem by renal dehydropeptidase-I. It is resistant to hydrolysis by most other beta-lactamases. Notable exceptions are the KPC beta-lactamases and Ambler Class B enzymes. amoxicillin-clavulanic acid Antibiotic An antibiotic cocktail containing the beta-lactam antibiotic Amoxicillin and the beta-lactamase inhibitor Clavulanic Acid (potassium clavulanate). carbapenem Drug Class Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity, and have a structure which renders them highly resistant to beta-lactamases. Carbapenem antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. cephalosporin Drug Class Cephalosporins are a class of beta-lactam antibiotics, containing the beta-lactam ring fused with a dihydrothiazolidine ring. Together with cephamycins they belong to a sub-group called cephems. Cephalosporin are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. cephamycin Drug Class Cephamycins are a group of beta-lactam antibiotics, very similar to cephalosporins. Together with cephalosporins, they form a sub-group of antibiotics known as cephems. Cephamycins are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The 7-alpha-methoxy group increases resistance to beta-lactamases. penam Drug Class Penams, often referred to as penicillins, are a group of antibiotics derived from Penicillium fungi. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases such as syphilis and Staphylococcus infections. Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are beta-lactam antibiotics in the penam sub-group, and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.
Perfect	QnrS1	protein homolog model	52116 - 52772(+)	6.836e-167	100 %
quinolone resistance protein (qnr) AMR Gene Family Qnr proteins are pentapeptide repeat proteins that mimic DNA and protect the cell from the activity of fluoroquinolone antibiotics ciprofloxacin Antibiotic Ciprofloxacin is a bacteriocidal fluoroquinolone. It blocks bacterial DNA replication by binding to the toposiomerase II or IV-DNA complex (or cleavable complex), thereby causing double-stranded breaks in the bacterial chromosome. levofloxacin Antibiotic Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class. Its main target is topoisomerase IV, inhibiting its function and disrupting DNA replication. moxifloxacin Antibiotic Moxifloxacin is a fourth generation synthetic fluoroquinolone chemotherapeutic agent, and has been shown to be significantly more active than levofloxacin (4 to 8 times more) against Streptococcus pneumoniae. It acts by inhibiting bacterial DNA topoisomerases. gatifloxacin Antibiotic Gatifloxacin is an 8-methoxy, 7-piperazinyl, 6-fluoroquinolone that can be taken orally or by intravenous administration. It is active against most Gram-positive and Gram-negative bacteria, but inactive against non-fermenting Gram-negative rods including Pseudomonas aeruginosa. nalidixic acid Antibiotic Nalidixic acid is a quinolone derivative of naphthyridine active against many enterobacteria, but ineffective against Ps aeruginosa, Gram-positive bacteria, and anaerobes. Acquired resistance is common in nalidixic acid treatments. norfloxacin Antibiotic Norfloxacin is a 6-fluoro, 7-piperazinyl quinolone with a wide range of activity against Gram-negative bacteria. It is inactive against most anaerobes. sparfloxacin Antibiotic Sparfloxacin is a dimethylpiperazinyl difluoroquinolone that acts by inhibiting DNA gyrase. It is active against aerobic Gram-positive and Gram-negative bacteria, as well as some mycobacteria. It has moderate activity against some anaerobes. fluoroquinolone antibiotic Drug Class The fluoroquinolones are a family of synthetic broad-spectrum antibiotics that are 4-quinolone-3-carboxylates. These compounds interact with topoisomerase II (DNA gyrase) to disrupt bacterial DNA replication, damage DNA, and cause cell death. antibiotic target protection Resistance Mechanism Protection of antibiotic action target from antibiotic binding, which process will result in antibiotic resistance.
Strict	floR	protein homolog model	137895 - 139109(-)	0	99.75 %
major facilitator superfamily (MFS) antibiotic efflux pump AMR Gene Family Directed pumping of antibiotic out of a cell to confer resistance. Major facilitator superfamily (MFS) transporters and ABC transporters comprise the two largest and most functionally diverse of the transporter superfamilies. However, MFS transporters are distinct from ABC transporters in both their primary sequence and structure and in the mechanism of energy coupling. As secondary transporters they are, like RND and SMR transporters, energized by the electrochemical proton gradient. chloramphenicol Antibiotic Chloramphenicol is a bacteriostatic antimicrobial originally derived from the bacterium Streptomyces venezuelae. It was the first antibiotic to be manufactured synthetically on a large scale. It functions by inhibiting peptidyl transferase activity of the bacterial ribosome, binding to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit and preventing peptide bond formation. florfenicol Antibiotic Florfenicol is a fluorine derivative of chloramphenicol, where the nitro group (-NO2) is substituted by a sulfomethyl group (-SO2CH3) and the hydroxyl group (-OH), by a fluorine group (-F). The action mechanism is the same as chloramphenicol's, where the antibiotic binds to the 23S RNA of the 50S subunit of bacterial ribosomes to inhibit protein synthesis. phenicol antibiotic Drug Class Phenicols are broad spectrum bacteriostatic antibiotics acting on bacterial protein synthesis. More specifically, the phenicols block peptide elongation by binding to the peptidyltansferase centre of the 70S ribosome. efflux pump complex or subunit conferring antibiotic resistance Efflux Component Efflux proteins that pump antibiotic out of a cell to confer resistance. antibiotic efflux Resistance Mechanism Antibiotic resistance via the transport of antibiotics out of the cell.
Strict	AAC(6')-Ib10	protein homolog model	142005 - 142634(+)	4.96421e-150	96.65 %
AAC(6') AMR Gene Family Acetylation of the aminoglycoside antibiotic on the amino group at position 6'. neomycin Antibiotic Neomycin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Neomycin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. dibekacin Antibiotic Dibekacin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Dibekacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. amikacin Antibiotic Amikacin is an aminoglycoside antibiotic that works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. sisomicin Antibiotic Sisomicin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Sisomicin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. netilmicin Antibiotic Netilmicin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. Netilmicin is not absorbed from the gut and is therefore only given by injection or infusion. It is only used in the treatment of serious infections particularly those resistant to gentamicin. kanamycin A Antibiotic Kanamycin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Kanamycin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. tobramycin Antibiotic Tobramycin is an aminoglycoside antibiotic used to treat different types of bacterial infections. Tobramycin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth. isepamicin Antibiotic A semi-synthetic derivative of gentamicin B (hydroxyamino propionyl genamicin B). It is modified to combat microbial inactivation and has a slightly larger spectrum of activity compared to other aminoglycosides, including Ser marcescens, Enterobacteria, and K pneumoniae. arbekacin Antibiotic A synthetic derivative (1-N-(4-amino-2-hydroxybutyryl) of dibekacin used in Japan. It is active against methicillin-resistant Staph. aureus and shows synergy with ampicillin when treating gentamicin and vancomycin resistant enterocci. gentamicin B Antibiotic Gentamicin B is a semisynthetic aminoglycoside antibacterial. aminoglycoside antibiotic Drug Class Aminoglycosides are a group of antibiotics that are mostly effective against Gram-negative bacteria. These molecules consist of aminated sugars attached to a dibasic cyclitol. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. antibiotic inactivation Resistance Mechanism Enzymatic inactivation of antibiotic to confer drug resistance.

Plasmid genes

AMR genes

Plasmid map

Notes

Characteristic genes

Antimicrobial resistance genes