ENTRY ko01501 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: antimicrobial PATHWAY_MAP ko01501 beta-Lactam resistance MODULE M00625 Methicillin resistance [PATH:ko01501] M00627 beta-Lactam resistance, Bla system [PATH:ko01501] M00649 Multidrug resistance, efflux pump AdeABC [PATH:ko01501] M00851 Carbapenem resistance [PATH:ko01501] DRUG D12817 Enmetazobactam (USAN/INN) REFERENCE PMID:23034325 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) DOI:10.1128/CMR.00043-12 REFERENCE PMID:21149619 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) DOI:10.1128/AAC.01252-10 REFERENCE PMID:20351243 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) DOI:10.1073/pnas.0912115107 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) DOI:10.1128/AAC.42.11.2799 REFERENCE PMID:23163477 AUTHORS Johnson JW, Fisher JF, Mobashery S TITLE Bacterial cell-wall recycling. JOURNAL Ann N Y Acad Sci 1277:54-75 (2013) DOI:10.1111/j.1749-6632.2012.06813.x REFERENCE PMID:22438804 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) DOI:10.1371/journal.ppat.1002571 REFERENCE PMID:19154333 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) DOI:10.1111/j.1365-2958.2008.06583.x REFERENCE PMID:18248419 AUTHORS Zapun A, Contreras-Martel C, Vernet T TITLE Penicillin-binding proteins and beta-lactam resistance. JOURNAL FEMS Microbiol Rev 32:361-85 (2008) DOI:10.1111/j.1574-6976.2007.00095.x REFERENCE PMID:19258280 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) DOI:10.1128/AAC.01024-08 REFERENCE PMID:15387820 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) DOI:10.1111/j.1365-2958.2004.04210.x REFERENCE PMID:11895293 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) DOI:10.2174/1568026013395605 REFERENCE PMID:15855496 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) DOI:10.1128/AAC.49.5.1782-1786.2005 REFERENCE PMID:15105114 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) DOI:10.1128/AAC.48.5.1630-1639.2004 REFERENCE PMID:16048914 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) DOI:10.1128/AAC.49.8.3129-3135.2005 REFERENCE PMID:22371895 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) DOI:10.1128/AAC.06422-11 REFERENCE PMID:21173183 AUTHORS Coyne S, Courvalin P, Perichon B TITLE Efflux-mediated antibiotic resistance in Acinetobacter spp. JOURNAL Antimicrob Agents Chemother 55:947-53 (2011) DOI:10.1128/AAC.01388-10 REFERENCE PMID:19026770 AUTHORS Nikaido H, Takatsuka Y TITLE Mechanisms of RND multidrug efflux pumps. JOURNAL Biochim Biophys Acta 1794:769-81 (2009) DOI:10.1016/j.bbapap.2008.10.004 REFERENCE PMID:17277059 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) DOI:10.1128/JB.01819-06 REFERENCE PMID:12222968 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) DOI:10.1007/s00018-002-8500-0 REFERENCE PMID:16143832 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) DOI:10.1007/s00018-005-5148-6 REL_PATHWAY ko00550 Peptidoglycan biosynthesis ///