KEGG   PATHWAY: ko00312Help
Entry
ko00312                     Pathway                                

Name
beta-Lactam resistance
Description
The beta-lactam antibiotics are the most widely used group of antibiotics, which exert their effect by interfering with the structural crosslinking of peptidoglycans in bacterial cell walls. Over the past decades, a rapid increase in the number of beta-lactam-resistant clinical isolates is observed. Bacterial resistance to beta-lactam antibiotics can be achieved by any of the following strategies: producing inactivating enzymes called beta-lactamases, altering the beta-lactam targets of penicillin-binding proteins (PBPs), reducing transport of beta-lactams into the periplasmic space via changes in porins, and using the mechanisms for exclusion of beta-lactams by way of efflux pumps. Resistance may result from intrinsic properties of organisms, through gene mutations, and through plasmid- and transposon-specified genes.
Class
Human Diseases; Drug resistance
BRITE hierarchy
Pathway map
beta-Lactam resistance
ko00312

All organismsOrtholog table
Module
M00625  
Methicillin resistance [PATH:ko00312]
M00626  
beta-Lactam resistance, penicillin-binding protein variants [PATH:ko00312]
M00627  
beta-Lactam resistance, Bla system [PATH:ko00312]
M00628  
beta-Lactam resistance, AmpC system [PATH:ko00312]
M00629  
beta-Lactam resistance, outer membrane pore variants [PATH:ko00312]
M00649  
Multidrug resistance, efflux pump AdeABC [PATH:ko00312]
M00654  
ParS-ParR (polymyxin-adaptive resistance) two-component regulatory system [PATH:ko00312]
M00655  
AdeS-AdeR two-component regulatory system [PATH:ko00312]
Drug
D00660  
Tazobactam (JP16/USAN/INN)
D01668  
Sultamicillin tosilate hydrate (JP16)
D02223  
Sulbactam sodium (JP16/USP)
D02370  
Clavulanate potassium (JP16/USP)
D03705  
Sulbactam benzathine (USAN)
D03706  
Sulbactam pivoxil (USAN)
D03707  
Tazobactam sodium (USAN)
D05972  
Sultamicillin (USAN/INN)
D07711  
Clavulanic acid (INN)
D08533  
Sulbactam (INN)
Orthology
K18093  
imipenem/basic amino acid-specific outer membrane pore [EC:3.4.21.-]
K09476  
outer membrane pore protein F
K09475  
outer membrane pore protein C
K08720  
outer membrane protein OmpU
K18133  
major outer membrane protein P.IB
K08218  
MFS transporter, PAT family, beta-lactamase induction signal transducer AmpG
K01207  
beta-N-acetylhexosaminidase [EC:3.2.1.52]
K17850  
LysR family transcriptional regulator, regulator of gene expression of beta-lactamase
K01467  
beta-lactamase class C [EC:3.5.2.6]
K15580  
oligopeptide transport system substrate-binding protein
K15581  
oligopeptide transport system permease protein
K15582  
oligopeptide transport system permease protein
K15583  
oligopeptide transport system ATP-binding protein
K10823  
oligopeptide transport system ATP-binding protein
K02172  
bla regulator protein blaR1
K02171  
BlaI family transcriptional regulator, penicillinase repressor
K17836  
beta-lactamase class A [EC:3.5.2.6]
K02547  
methicillin resistance protein
K02546  
BlaI family transcriptional regulator, methicillin resistance regulatory protein
K02545  
penicillin-binding protein 2 prime
K18072  
two-component system, OmpR family, sensor kinase ParS [EC:2.7.13.3]
K18073  
two-component system, OmpR family, response regulator ParR
K18148  
release factor H-coupled RctB family protein
K18129  
TetR/AcrR family transcriptional regulator, mexXY operon repressor
K18094  
membrane fusion protein
K18095  
multidrug efflux pump
K18130  
TetR/AcrR family transcriptional regulator, transcriptional repressor NalC
K18150  
antirepressor for MexR
K18131  
MarR family transcriptional regulator, repressor of the mexAB-oprM multidrug resistance operon
K18135  
TetR/AcrR family transcriptional regulator, repressor of the mexAB-oprM multidrug resistance operon
K18136  
TetR/AcrR family transcriptional regulator, multidrug resistance operon repressor
K18137  
TetR/AcrR family transcriptional regulator, repressor of of the adeIJK operon
K03585  
membrane fusion protein
K18138  
multidrug efflux pump
K18139  
outer membrane protein
K18143  
two-component system, OmpR family, sensor histidine kinase AdeS [EC:2.7.13.3]
K18144  
two-component system, OmpR family, response regulator AdeR
K18145  
membrane fusion protein
K18146  
multidrug efflux pump
K18147  
outer membrane protein
K12340  
outer membrane channel protein
K18104  
ATP-binding cassette, subfamily B, bacterial AbcA/BmrA [EC:3.6.3.44]
K18149  
penicillin-binding protein
K12552  
penicillin-binding protein 1 [EC:3.4.-.-]
K12553  
penicillin-binding protein 3 [EC:3.4.-.-]
K05366  
penicillin-binding protein 1A [EC:3.4.-.- 2.4.1.-]
K03693  
penicillin-binding protein
K12555  
penicillin-binding protein 2A [EC:2.3.2.- 2.4.1.129]
K00687  
penicillin-binding protein 2B [EC:2.3.2.-]
K12556  
penicillin-binding protein 2X [EC:2.3.2.-]
K05515  
penicillin-binding protein 2
K03587  
cell division protein FtsI (penicillin-binding protein 3)
K17837  
metallo-beta-lactamase class B [EC:3.5.2.6]
K17838  
beta-lactamase class D [EC:3.5.2.6]
Compound
C00039  
DNA
C03438  
beta-Lactam antibiotics
C04702  
UDPMurAc(oyl-L-Ala-D-gamma-Glu-L-Lys-D-Ala-D-Ala)
D07746  
Colistin (INN)
D08401  
Polymyxin B (INN)
Reference
  Authors
Fernandez L, Hancock RE
  Title
Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance.
  Journal
Clin Microbiol Rev 25:661-81 (2012)
Reference
  Authors
Muller C, Plesiat P, Jeannot K
  Title
A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and beta-lactams in Pseudomonas aeruginosa.
  Journal
Antimicrob Agents Chemother 55:1211-21 (2011)
Reference
  Authors
Tanabe M, Nimigean CM, Iverson TM
  Title
Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB.
  Journal
Proc Natl Acad Sci U S A 107:6811-6 (2010)
Reference
PMID:9797206
  Authors
Gill MJ, Simjee S, Al-Hattawi K, Robertson BD, Easmon CS, Ison CA
  Title
Gonococcal resistance to beta-lactams and tetracycline involves mutation in loop  3 of the porin encoded at the penB locus.
  Journal
Antimicrob Agents Chemother 42:2799-803 (1998)
Reference
  Authors
Johnson JW, Fisher JF, Mobashery S
  Title
Bacterial cell-wall recycling.
  Journal
Ann N Y Acad Sci 1277:54-75 (2013)
Reference
  Authors
Amoroso A, Boudet J, Berzigotti S, Duval V, Teller N, Mengin-Lecreulx D, Luxen A, Simorre JP, Joris B
  Title
A peptidoglycan fragment triggers beta-lactam resistance in Bacillus licheniformis.
  Journal
PLoS Pathog 8:e1002571 (2012)
Reference
  Authors
Sala C, Haouz A, Saul FA, Miras I, Rosenkrands I, Alzari PM, Cole ST
  Title
Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis.
  Journal
Mol Microbiol 71:1102-16 (2009)
Reference
  Authors
Zapun A, Contreras-Martel C, Vernet T
  Title
Penicillin-binding proteins and beta-lactam resistance.
  Journal
FEMS Microbiol Rev 32:361-85 (2008)
Reference
  Authors
Vettoretti L, Plesiat P, Muller C, El Garch F, Phan G, Attree I, Ducruix A, Llanes C
  Title
Efflux unbalance in Pseudomonas aeruginosa isolates from cystic fibrosis patients.
  Journal
Antimicrob Agents Chemother 53:1987-97 (2009)
Reference
  Authors
Cao L, Srikumar R, Poole K
  Title
MexAB-OprM hyperexpression in NalC-type multidrug-resistant Pseudomonas aeruginosa: identification and characterization of the nalC gene encoding a repressor of PA3720-PA3719.
  Journal
Mol Microbiol 53:1423-36 (2004)
Reference
  Authors
Poole K, Srikumar R
  Title
Multidrug efflux in Pseudomonas aeruginosa: components, mechanisms and clinical significance.
  Journal
Curr Top Med Chem 1:59-71 (2001)
Reference
  Authors
Sobel ML, Hocquet D, Cao L, Plesiat P, Poole K
  Title
Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug  resistance in laboratory and clinical isolates of Pseudomonas aeruginosa.
  Journal
Antimicrob Agents Chemother 49:1782-6 (2005)
Reference
  Authors
Kaczmarek FS, Gootz TD, Dib-Hajj F, Shang W, Hallowell S, Cronan M
  Title
Genetic and molecular characterization of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin.
  Journal
Antimicrob Agents Chemother 48:1630-9 (2004)
Reference
  Authors
Dean CR, Narayan S, Daigle DM, Dzink-Fox JL, Puyang X, Bracken KR, Dean KE, Weidmann B, Yuan Z, Jain R, Ryder NS
  Title
Role of the AcrAB-TolC efflux pump in determining susceptibility of Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415.
  Journal
Antimicrob Agents Chemother 49:3129-35 (2005)
Reference
  Authors
Rosenfeld N, Bouchier C, Courvalin P, Perichon B
  Title
Expression of the resistance-nodulation-cell division pump AdeIJK in Acinetobacter baumannii is regulated by AdeN, a TetR-type regulator.
  Journal
Antimicrob Agents Chemother 56:2504-10 (2012)
Reference
  Authors
Coyne S, Courvalin P, Perichon B
  Title
Efflux-mediated antibiotic resistance in Acinetobacter spp.
  Journal
Antimicrob Agents Chemother 55:947-53 (2011)
Reference
  Authors
Nikaido H, Takatsuka Y
  Title
Mechanisms of RND multidrug efflux pumps.
  Journal
Biochim Biophys Acta 1794:769-81 (2009)
Reference
  Authors
Truong-Bolduc QC, Hooper DC
  Title
The transcriptional regulators NorG and MgrA modulate resistance to both quinolones and beta-lactams in Staphylococcus aureus.
  Journal
J Bacteriol 189:2996-3005 (2007)
Reference
  Authors
Sauvage E, Kerff F, Fonze E, Herman R, Schoot B, Marquette JP, Taburet Y, Prevost D, Dumas J, Leonard G, Stefanic P, Coyette J, Charlier P
  Title
The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.
  Journal
Cell Mol Life Sci 59:1223-32 (2002)
Reference
  Authors
Fuda CC, Fisher JF, Mobashery S
  Title
Beta-lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome.
  Journal
Cell Mol Life Sci 62:2617-33 (2005)

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