KEGG image  Antimicrobial Resistance: KEGG Signatures

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Signature KOs for antimicrobial resistance

beta-Lactamase KOs (see also beta-lactamase genes)

Class KO Name Threat Level Drug group
MT A 2b K18698 beta-lactamase class A TEM MT A3 B1 B4 B6 B7 B8 B12 Extended-spectrum cephalosporin (DG01776, DG01777),
Monobactam (DG01454)
K18699 beta-lactamase class A SHV MT B1 B4 B5
K18767 beta-lactamase class A CTX-M MT B1 B4 B7 B8 B9
K18797 beta-lactamase class A PER MT B1 B4 B6 B7 B8
K19097 beta-lactamase class A VEB MT B1 B4 B6 Extended-spectrum cephalosporin (DG01776, DG01777)
K19317 beta-lactamase class A BEL MT B6
K18796 beta-lactamase class A LAP MT
2f K18768 beta-lactamase class A KPC MT A2 B1 B6 Carbapenem (DG01458)
K18970 beta-lactamase class A GES MT B1 B4 B6 Extended-spectrum cephalosporin (DG01776, DG01777),
Carbapenem (DG01458)
K19316 beta-lactamase class A IMI/SME MT A2 Carbapenem (DG01458)
K22346 beta-lactamase class A SME MT A2 Carbapenem (DG01458)
Second-generation cephalosporin (DG01775)
Monobactam (DG01454)
2c K18795 beta-lactamase class A CARB-1 MT B6 B7 Carbenicillin (DG00519)
K19218 beta-lactamase class A CARB-5 MT B1 Carbenicillin (DG00519)
K19217 beta-lactamase class A CARB-17 MT
D 2d K18794 beta-lactamase class D OXA-51 MT B1 Carbapenem (DG01458)
K19318 beta-lactamase class D OXA-213 MT B1 Carbapenem (DG01458)
K18971 beta-lactamase class D OXA-24 MT B1 Carbapenem (DG01458)
K18793 beta-lactamase class D OXA-23 MT A2 B1 Carbapenem (DG01458)
K19319 beta-lactamase class D OXA-134 MT B1 Carbapenem (DG01458)
K19320 beta-lactamase class D OXA-211 MT B1 Carbapenem (DG01458)
K19321 beta-lactamase class D OXA-214 MT B1 Extended spectrum penicillin (DG01780)
Carbapenem (DG01458) (weak)
K19322 beta-lactamase class D OXA-229 MT B1 Carbapenem (DG01458)
K18972 beta-lactamase class D OXA-58 MT B1 Carbapenem (DG01458)
K21266 beta-lactamase class D OXA-286 MT B1
K18973 beta-lactamase class D OXA-50 MT B6 Narrow-spectrum penicillin (DG01779)
K19211 beta-lactamase class D OXA-62 MT Carbapenem (DG01458)
K18791 beta-lactamase class D OXA-2 MT B1 B4 B6 B7 B8 Extended-spectrum cephalosporin (DG01776, DG01777)
K18792 beta-lactamase class D OXA-10 MT B1 B4 B6 Extended-spectrum cephalosporin (DG01776, DG01777)
K18976 beta-lactamase class D OXA-48 MT A2 Carbapenem (DG01458)
K19210 beta-lactamase class D OXA-61 MT B2 Narrow-spectrum penicillin (DG01779)
K19212 beta-lactamase class D OXA-63 MT Narrow-spectrum penicillin (DG01779)
K18790 beta-lactamase class D OXA-1 MT B4 B6 B7 B9 Extended-spectrum cephalosporin (DG01776, DG01777)
Extended spectrum penicillin (DG01780)
K19098 beta-lactamase class D OXA-9 MT Narrow-spectrum penicillin (DG01779)
K19209 beta-lactamase class D OXA-42 MT Narrow-spectrum penicillin (DG01779)
K19213 beta-lactamase class D OXA-12 MT Narrow-spectrum penicillin (DG01779)
K21276 beta-lactamase class D OXA-22 MT Narrow-spectrum penicillin (DG01779)
K21277 beta-lactamase class D OXA-60 MT Narrow-spectrum penicillin (DG01779)
Carbapenem (DG01458) (weak)
K22331 beta-lactamase class D OXA-184 MT B2
K22332 beta-lactamase class D OXA-548 MT
K22333 beta-lactamase class D OXA-493 MT
K22334 beta-lactamase class D OXA-464 MT
K22335 beta-lactamase class D OXA-114 MT Extended spectrum penicillin (DG01780)
Third-generation cephalosporin (DG01776)
K22351 beta-lactamase class D OXA-209 MT Extended-spectrum penicillin (DG01780)
K22352 beta-lactamase class D OXA-29 MT Extended-spectrum penicillin (DG01780)
C 1 K19095 beta-lactamase class C CMY-1 MT B4 Extended-spectrum cephalosporin (DG01776, DG01777)
K19096 beta-lactamase class C CMY-2 MT B4 B7 Second-generation cephalosporin (DG01775)
Third-generation cephalosporin (DG01776)
K19100 beta-lactamase class C DHA MT
K19101 beta-lactamase class C FOX MT
K19214 beta-lactamase class C ACC MT
K19215 beta-lactamase class C ACT/MIR MT Extended-spectrum penicillin (DG01780)
Second-generation cephalosporin (DG01775)
K20319 beta-lactamase class C ADC MT
K20320 beta-lactamase class C PDC MT
B 3 K18782 metallo-beta-lactamase class B IMP MT A2 B1 B4 B6 B9 Extended-spectrum cephalosporin (DG01776, DG01777),
Carbapenem (DG01458)
K18781 metallo-beta-lactamase class B VIM MT B4 B6 Extended-spectrum cephalosporin (DG01776, DG01777),
Carbapenem (DG01458)
K18780 metallo-beta-lactamase class B NDM MT A2 B1 Carbapenem (DG01458)
K19099 metallo-beta-lactamase class B GIM MT A2 B6 Carbapenem (DG01458)
K19216 metallo-beta-lactamase class B IND MT Carbapenem (DG01458)

Other resistance KOs (see also aminoglycoside resistance genes, tetracycline resistance genes,
macrolide resistance genes, phenicol resistance genes, trimethoprim resistance genes)

KO Name Threat Level Drug group
MT K17840 aminoglycoside 2'-N-acetyltransferase I MT B6 B12 Aminoglycoside (DG01447)
K03395 aminoglycoside 3-N-acetyltransferase I MT B1 B6 B7
K19275 aminoglycoside 3-N-acetyltransferase II MT B1 B7
K19276 aminoglycoside 3-N-acetyltransferase IV MT B6
K19277 aminoglycoside 3-N-acetyltransferase VI MT B7
K19278 aminoglycoside 6'-N-acetyltransferase Ib MT B1 B6
K19301 aminoglycoside 6'-N-acetyltransferase II MT B1 B6
K18815 aminoglycoside 6'-N-acetyltransferase I MT B1 B6 B7
K18816 aminoglycoside 6'-N-acetyltransferase I MT B1 B6 B7 B11
K17881 aminoglycoside 2''-adenylyltransferase MT B1
K19544 aminoglycoside 4'-adenylyltransferase MT B6
K19272 aminoglycoside 3'-phosphotransferase I MT B1 B7
K19300 aminoglycoside 3'-phosphotransferase II MT B6
K19299 aminoglycoside 3'-phosphotransferase III MT B11
K19274 aminoglycoside 3'-phosphotransferase VI MT B1
K19315 aminoglycoside 3'-phosphotransferase XV MT B6
K10673 streptomycin 3"-kinase MT B1 B6 B7
K04343 streptomycin 6-kinase MT B1 B6 B7
K18845 16S rRNA (guanine(1405)-N(7))-methyltransferase MT B1 B6
MT K18220 ribosomal protection tetracycline resistance protein MT A1 Tetracycline (DG00005)
MT K00561 23S rRNA (adenine-N6)-dimethyltransferase MT B11 Macrolide antibiotic (DG01551)
K18231 macrolide transport system ATP-binding/permease protein MT B1 B11
K06979 macrolide phosphotransferase MT B1
K08217 MFS transporter, DHA3 family, macrolide efflux protein MT B7 B11
MT K18552 MFS transporter, DHA1 family,
florfenicol/chloramphenicol resistance protein
MT B6 B7 Phenicol (DG01576)
K19271 chloramphenicol O-acetyltransferase type A MT A3 B1 B6 B7 B11
K00638 chloramphenicol O-acetyltransferase type B MT B1 B6 B7
K18554 chloramphenicol 3-O phosphotransferase MT B12
MT K18589 dihydrofolate reductase DfrA MT B1 B6 B7 Trimethoprim (DG01581)
K19643 dihydrofolate reductase DfrA MT B1
K18590 dihydrofolate reductase DfrA MT B7
K19644 dihydrofolate reductase DfrA MT B7
K19645 dihydrofolate reductase DfrB MT B6 B7

Signature modules for antimicrobial resistance

Module Name Threat Level
MT M00625 Methicillin resistance MT B10
M00627 beta-Lactam resistance, Bla system MT B10
M00745 Imipenem resistance, repression of porin OprD MT B6
M00651 Vancomycin resistance, D-Ala-D-Lac type MT B5
M00652 Vancomycin resistance, D-Ala-D-Ser type MT B5
M00704 Tetracycline resistance, efflux pump Tet38 MT B10
M00725 CAMP resistance, dltABCD operon MT B10
M00726 CAMP resistance, lysyl-phosphatidylglycerol (L-PG) synthase MprF MT B10
M00730 CAMP resistance, VraFG transporter MT B10
M00744 CAMP resistance, protease PgtE MT B7 B8
M00718 Multidrug resistance, efflux pump MexAB-OprM MT B6
M00639 Multidrug resistance, efflux pump MexCD-OprJ MT B6
M00641 Multidrug resistance, efflux pump MexEF-OprN MT B6
M00642 Multidrug resistance, efflux pump MexJK-OprM MT B1 B6
M00643 Multidrug resistance, efflux pump MexXY-OprM MT B6
M00769 Multidrug resistance, efflux pump MexPQ-OpmE MT B6
M00649 Multidrug resistance, efflux pump AdeABC MT B1
M00696 Multidrug resistance, efflux pump AcrEF-TolC MT A2 B4 B7 B8
M00697 Multidrug resistance, efflux pump MdtEF-TolC MT B9
M00698 Multidrug resistance, efflux pump BpeEF-OprC MT B1
M00700 Multidrug resistance, efflux pump AbcA MT B10
M00702 Multidrug resistance, efflux pump NorB MT B10 C1
M00714 Multidrug resistance, efflux pump QacA MT B10 C1
M00705 Multidrug resistance, efflux pump MepA MT B10 C1
M00746 Multidrug resistance, repression of porin OmpF MT B7 B8 B9

Threat level by CDC

A. Urgent threats
A1. Clostridium difficile
A2. Carbapenem-resistant Enterobacteriaceae (CRE)
A3. Drug-resistant Neisseria gonorrhoeae
B. Serious threats
B1. Multidrug-resistant Acinetobacter
B2. Drug-resistant Campylobacter
B3. Fluconazole-resistant Candida (a fungus)
B4. Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBLs)
B5. Vancomycin-resistant Enterococcus (VRE)
B6. Multidrug-resistant Pseudomonas aeruginosa
B7. Drug-resistant non-typhoidal Salmonella
B8. Drug-resistant Salmonella enterica serovar Typhi
B9. Drug-resistant Shigella
B10. Methicillin-resistant Staphylococcus aureus (MRSA)
B11. Drug-resistant Streptococcus pneumoniae
B12. Drug-resistant tuberculosis
C. Concerning threats
C1. Vancomycin-resistant Staphylococcus aureus (VRSA)
C2. Erythromycin-resistant group A Streptococcus
C3. Clindamycin-resistant group B Streptococcus

According to: Antibiotic Resistance Threats in the United States, 2013

Priority pathogens list by WHO

Priority 1: Critical
1. Acinetobacter baumannii, carbapenem-resistant
2. Pseudomonas aeruginosa, carbapenem-resistant
3. Enterobacteriaceae, carbapenem-resistant, ESBL-producing
Priority 2: High
1. Enterococcus faecium, vancomycin-resistant
2. Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant
3. Helicobacter pylori, clarithromycin-resistant
4. Campylobacter spp., fluoroquinolone-resistant
5. Salmonellae, fluoroquinolone-resistant
6. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant
Priority 3: Medium
1. Streptococcus pneumoniae, penicillin-non-susceptible
2. Haemophilus influenzae, ampicillin-resistant
3. Shigella spp., fluoroquinolone-resistant

According to: WHO priority pathogens list for R&D of new antibiotics, 2017

Last updated: February 1, 2018