ENTRY ko01503 Pathway NAME Cationic antimicrobial peptide (CAMP) resistance DESCRIPTION Cationic antimicrobial peptides (CAMPs) play an important role in host defense against microbial infection and are key components of the innate immune response. These are found among all classes of life ranging from prokaryotes to humans. In addition to the natural peptides, thousands of synthetic variants have been produced. CAMPs weaken the integrity of the bacterial inner and outer membranes and subsequently kill bacterial cells. On the other hand, bacteria have developed a number of mechanisms against CAMPs. These resistance mechanisms include decreased affinity to CAMPs by substitution of anionic cell surface constituents with cationic molecules; biosynthesis and crosslinking of cell envelope components; external trapping mechanisms that bind or neutralize the CAMPs by direct secretion of proteins, or the release of CAMPs binding molecules from the host cell surface; membrane efflux pumps; and production of peptidases. CLASS Human Diseases; Drug resistance: antimicrobial PATHWAY_MAP ko01503 Cationic antimicrobial peptide (CAMP) resistance MODULE M00725 Cationic antimicrobial peptide (CAMP) resistance, dltABCD operon [PATH:ko01503] M00726 Cationic antimicrobial peptide (CAMP) resistance, lysyl-phosphatidylglycerol (L-PG) synthase MprF [PATH:ko01503] M00730 Cationic antimicrobial peptide (CAMP) resistance, VraFG transporter [PATH:ko01503] REFERENCE PMID:16450883 AUTHORS Nizet V TITLE Antimicrobial peptide resistance mechanisms of human bacterial pathogens. JOURNAL Curr Issues Mol Biol 8:11-26 (2006) REFERENCE PMID:22339775 AUTHORS Gruenheid S, Le Moual H TITLE Resistance to antimicrobial peptides in Gram-negative bacteria. JOURNAL FEMS Microbiol Lett 330:81-9 (2012) DOI:10.1111/j.1574-6968.2012.02528.x REFERENCE PMID:25419466 AUTHORS Nawrocki KL, Crispell EK, McBride SM TITLE Antimicrobial Peptide Resistance Mechanisms of Gram-Positive Bacteria. JOURNAL Antibiotics (Basel) 3:461-492 (2014) DOI:10.3390/antibiotics3040461 REFERENCE PMID:22799636 AUTHORS Anaya-Lopez JL, Lopez-Meza JE, Ochoa-Zarzosa A TITLE Bacterial resistance to cationic antimicrobial peptides. JOURNAL Crit Rev Microbiol 39:180-95 (2013) DOI:10.3109/1040841X.2012.699025 REFERENCE PMID:23748343 AUTHORS Needham BD, Trent MS TITLE Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. JOURNAL Nat Rev Microbiol 11:467-81 (2013) DOI:10.1038/nrmicro3047 REFERENCE PMID:17928292 AUTHORS Yan A, Guan Z, Raetz CR TITLE An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli. JOURNAL J Biol Chem 282:36077-89 (2007) DOI:10.1074/jbc.M706172200 REFERENCE PMID:15695810 AUTHORS Breazeale SD, Ribeiro AA, McClerren AL, Raetz CR. TITLE A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose. JOURNAL J Biol Chem 280:14154-67 (2005) DOI:10.1074/jbc.M414265200 REFERENCE PMID:25505462 AUTHORS Olaitan AO, Morand S, Rolain JM TITLE Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. JOURNAL Front Microbiol 5:643 (2014) DOI:10.3389/fmicb.2014.00643 REFERENCE PMID:21645016 AUTHORS Martinez JL, Rojo F TITLE Metabolic regulation of antibiotic resistance. JOURNAL FEMS Microbiol Rev 35:768-89 (2011) DOI:10.1111/j.1574-6976.2011.00282.x REFERENCE PMID:20843473 AUTHORS Falagas ME, Rafailidis PI, Matthaiou DK TITLE Resistance to polymyxins: Mechanisms, frequency and treatment options. JOURNAL Drug Resist Updat 13:132-8 (2010) DOI:10.1016/j.drup.2010.05.002 REFERENCE PMID:19243444 AUTHORS Gooderham WJ, Hancock RE TITLE Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. JOURNAL FEMS Microbiol Rev 33:279-94 (2009) DOI:10.1111/j.1574-6976.2008.00135.x REFERENCE PMID:15205413 AUTHORS Lee H, Hsu FF, Turk J, Groisman EA TITLE The PmrA-regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica. JOURNAL J Bacteriol 186:4124-33 (2004) DOI:10.1128/JB.186.13.4124-4133.2004 REFERENCE PMID:24034668 AUTHORS Wang D, Seeve C, Pierson LS 3rd, Pierson EA TITLE Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa. JOURNAL BMC Genomics 14:618 (2013) DOI:10.1186/1471-2164-14-618 REFERENCE PMID:22123691 AUTHORS Falord M, Karimova G, Hiron A, Msadek T TITLE GraXSR proteins interact with the VraFG ABC transporter to form a five-component system required for cationic antimicrobial peptide sensing and resistance in Staphylococcus aureus. JOURNAL Antimicrob Agents Chemother 56:1047-58 (2012) DOI:10.1128/AAC.05054-11 REFERENCE PMID:16715050 AUTHORS Rowley G, Spector M, Kormanec J, Roberts M TITLE Pushing the envelope: extracytoplasmic stress responses in bacterial pathogens. JOURNAL Nat Rev Microbiol 4:383-94 (2006) DOI:10.1038/nrmicro1394 REFERENCE PMID:23267440 AUTHORS Piek S, Kahler CM TITLE A comparison of the endotoxin biosynthesis and protein oxidation pathways in the biogenesis of the outer membrane of Escherichia coli and Neisseria meningitidis. JOURNAL Front Cell Infect Microbiol 2:162 (2012) DOI:10.3389/fcimb.2012.00162 REFERENCE PMID:25294881 AUTHORS Weatherspoon-Griffin N, Yang D, Kong W, Hua Z, Shi Y TITLE The CpxR/CpxA two-component regulatory system up-regulates the multidrug resistance cascade to facilitate Escherichia coli resistance to a model antimicrobial peptide. JOURNAL J Biol Chem 289:32571-82 (2014) DOI:10.1074/jbc.M114.565762 REFERENCE PMID:22092948 AUTHORS Vogt SL, Raivio TL TITLE Just scratching the surface: an expanding view of the Cpx envelope stress response. JOURNAL FEMS Microbiol Lett 326:2-11 (2012) DOI:10.1111/j.1574-6968.2011.02406.x REFERENCE PMID:22072973 AUTHORS Shelton CL, Raffel FK, Beatty WL, Johnson SM, Mason KM TITLE Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus. JOURNAL PLoS Pathog 7:e1002360 (2011) DOI:10.1371/journal.ppat.1002360 REFERENCE PMID:19609257 AUTHORS Otto M TITLE Staphylococcus epidermidis--the 'accidental' pathogen. JOURNAL Nat Rev Microbiol 7:555-67 (2009) DOI:10.1038/nrmicro2182 REFERENCE PMID:21986630 AUTHORS Yang SJ, Bayer AS, Mishra NN, Meehl M, Ledala N, Yeaman MR, Xiong YQ, Cheung AL TITLE The Staphylococcus aureus two-component regulatory system, GraRS, senses and confers resistance to selected cationic antimicrobial peptides. JOURNAL Infect Immun 80:74-81 (2012) DOI:10.1128/IAI.05669-11 REFERENCE PMID:12366839 AUTHORS Schmidtchen A, Frick IM, Andersson E, Tapper H, Bjorck L TITLE Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. JOURNAL Mol Microbiol 46:157-68 (2002) DOI:10.1046/j.1365-2958.2002.03146.x REFERENCE PMID:23554414 AUTHORS Beceiro A, Tomas M, Bou G TITLE Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? JOURNAL Clin Microbiol Rev 26:185-230 (2013) DOI:10.1128/CMR.00059-12 REL_PATHWAY ko00520 Amino sugar and nucleotide sugar metabolism ko00540 Lipopolysaccharide biosynthesis ko02020 Two-component system ko05150 Staphylococcus aureus infection ///