Abstract
The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. Antibiotic resistance has become a major clinical problem today. In addition, multidrug resistance also develops various structurally and functionally unrelated toxic compounds. To overcome this problem, a new target efflux pump was recognized that, if inhibited, reduces the level of resistance or potentiates or produces a synergistic effect in combination with antibiotics. Keeping this in view, the present review article aims to describe the families of efflux pumps and the various natural components to be employed as good efflux pump inhibitors.
Keywords: Efflux pump, EPIs, families, MDR, drug resistance, piperine.
Graphical Abstract
[http://dx.doi.org/10.1353/pbm.1989.0003] [PMID: 2648321]
[PMID: 3879679]
[http://dx.doi.org/10.1351/pac200274101957]
[http://dx.doi.org/10.1126/science.8153626]
[http://dx.doi.org/10.1021/jf0302714] [PMID: 12952418]
[http://dx.doi.org/10.1086/514920] [PMID: 9710669]
[http://dx.doi.org/10.1016/S1369-5274(98)80083-0] [PMID: 10066525]
[http://dx.doi.org/10.1016/S0006-2952(00)00291-4] [PMID: 10874120]
[http://dx.doi.org/10.1021/np050227d] [PMID: 16562846]
[http://dx.doi.org/10.1016/j.bbrc.2004.09.146] [PMID: 15485663]
[http://dx.doi.org/10.1016/S0006-291X(80)80247-6] [PMID: 6990931]
[http://dx.doi.org/10.1073/pnas.77.7.3974] [PMID: 7001450]
[http://dx.doi.org/10.1016/j.sbi.2015.07.015] [PMID: 26282926]
[http://dx.doi.org/10.1128/MMBR.64.4.672-693.2000] [PMID: 11104814]
[http://dx.doi.org/10.1146/annurev.micro.61.080706.093329] [PMID: 18537473]
[http://dx.doi.org/10.3390/molecules22030468] [PMID: 28294992]
[http://dx.doi.org/10.1126/science.1125629] [PMID: 16675700]
[http://dx.doi.org/10.1073/pnas.1311485110] [PMID: 24127585]
[http://dx.doi.org/10.1038/emboj.2010.309] [PMID: 21131908]
[http://dx.doi.org/10.1038/nature12042] [PMID: 23542591]
[http://dx.doi.org/10.1038/nature14909] [PMID: 26416735]
[http://dx.doi.org/10.1016/j.drup.2016.04.003] [PMID: 27449594]
[http://dx.doi.org/10.3389/fmicb.2016.01483] [PMID: 27708632]
[http://dx.doi.org/10.1016/j.bbrc.2009.01.081] [PMID: 19171121]
[http://dx.doi.org/10.1074/jbc.M206983200] [PMID: 12130659]
[http://dx.doi.org/10.1039/b413734p] [PMID: 16047044]
[http://dx.doi.org/10.1128/JB.182.8.2307-2310.2000] [PMID: 10735876]
[http://dx.doi.org/10.1248/bpb.25.1533] [PMID: 12499635]
[http://dx.doi.org/10.1021/bi960094i] [PMID: 8679552]
[http://dx.doi.org/10.1038/nature13205] [PMID: 24747401]
[http://dx.doi.org/10.3389/fmicb.2015.00377] [PMID: 25972857]
[http://dx.doi.org/10.4103/1947-2714.183015] [PMID: 27298819]
[http://dx.doi.org/10.3389/fmicb.2015.00660] [PMID: 26217310]
[http://dx.doi.org/10.1002/mbo3.182] [PMID: 24942069]
[http://dx.doi.org/10.1128/JB.02607-14] [PMID: 25802299]
[http://dx.doi.org/10.1016/j.bbapap.2008.10.004] [PMID: 19026770]
[http://dx.doi.org/10.1128/JB.178.20.5853-5859.1996] [PMID: 8830678]
[PMID: 11321576]
[http://dx.doi.org/10.1128/JB.176.22.6957-6964.1994] [PMID: 7961458]
[http://dx.doi.org/10.1146/annurev.cb.08.110192.000435] [PMID: 1282354]
[http://dx.doi.org/10.1038/nature05155] [PMID: 16943773]
[http://dx.doi.org/10.1021/bi0362018] [PMID: 15182191]
[http://dx.doi.org/10.1021/bi300762p] [PMID: 22950454]
[http://dx.doi.org/10.1073/pnas.0709388104] [PMID: 18024585]
[http://dx.doi.org/10.1046/j.1365-2958.1999.01162.x] [PMID: 9987140]
[http://dx.doi.org/10.1016/j.drup.2016.06.007] [PMID: 27620952]
[http://dx.doi.org/10.1128/CMR.19.2.382-402.2006] [PMID: 16614254]
[http://dx.doi.org/10.1016/j.tube.2015.01.005] [PMID: 25680943]
[http://dx.doi.org/10.1146/annurev.biochem.78.082907.145923] [PMID: 19231985]
[http://dx.doi.org/10.2165/11317030-000000000-00000] [PMID: 19678712]
[http://dx.doi.org/10.1016/S0889-8588(01)00016-8] [PMID: 12094476]
[http://dx.doi.org/10.1093/jac/46.5.852] [PMID: 11062217]
[PMID: 12139181]
[http://dx.doi.org/10.1016/S0140-6736(01)05410-1] [PMID: 11476839]
[http://dx.doi.org/10.1016/S0002-9343(98)00354-4]
[http://dx.doi.org/10.3201/eid0501.990118] [PMID: 10081683]
[http://dx.doi.org/10.1093/infdis/163.6.1279] [PMID: 2037793]
[http://dx.doi.org/10.1128/AAC.35.9.1911] [PMID: 1952866]
[http://dx.doi.org/10.2307/30140945] [PMID: 7759821]
[PMID: 12418544]
[http://dx.doi.org/10.1016/j.bmc.2007.04.023] [PMID: 17498961]
[http://dx.doi.org/10.1007/s11101-015-9436-y]
[http://dx.doi.org/10.1093/jac/dkl460] [PMID: 17145734]
[http://dx.doi.org/10.1055/s-2008-1074518] [PMID: 18446673]
[http://dx.doi.org/10.1128/AAC.37.1.128] [PMID: 8431010]
[http://dx.doi.org/10.1073/pnas.030540597] [PMID: 10677479]
[http://dx.doi.org/10.1016/j.phytochem.2005.06.008] [PMID: 16051285]
[http://dx.doi.org/10.1016/j.phytochem.2004.10.009] [PMID: 15561190]
[http://dx.doi.org/10.1093/jac/dks232] [PMID: 22807321]
[http://dx.doi.org/10.1016/j.biochi.2005.04.012] [PMID: 15951096]
[http://dx.doi.org/10.1128/AAC.50.2.810-812.2006] [PMID: 16436753]
[http://dx.doi.org/10.1093/jac/dkq186] [PMID: 20525733]
[http://dx.doi.org/10.1093/jac/40.3.458] [PMID: 9338508]
[http://dx.doi.org/10.1128/AAC.43.2.335] [PMID: 9925528]
[http://dx.doi.org/10.1093/jac/42.6.807] [PMID: 10052906]
[http://dx.doi.org/10.1002/(SICI)1099-1573(200003)14:2<139::AID-PTR608>3.0.CO;2-8] [PMID: 10685116]
[http://dx.doi.org/10.1016/S0966-842X(01)02175-8] [PMID: 11597450]
[http://dx.doi.org/10.1016/j.bmc.2012.05.025] [PMID: 22682300]
[http://dx.doi.org/10.1016/j.bmcl.2006.12.059] [PMID: 17275293]
[http://dx.doi.org/10.1016/S0924-8579(03)00085-2] [PMID: 12842327]
[http://dx.doi.org/10.1128/AAC.35.7.1267] [PMID: 1929280]
[http://dx.doi.org/10.1128/CMR.13.4.686] [PMID: 11023964]
[http://dx.doi.org/10.1016/j.femsle.2005.02.034] [PMID: 15837373]
[http://dx.doi.org/10.1021/np030409c] [PMID: 15043439]
[http://dx.doi.org/10.1128/AAC.48.6.1968-1973.2004] [PMID: 15155186]
[http://dx.doi.org/10.1111/j.1348-0421.2005.tb03732.x] [PMID: 15840965]
[http://dx.doi.org/10.1016/S0924-8579(03)00200-0] [PMID: 13678829]
[http://dx.doi.org/10.1021/np800148w] [PMID: 18500841]
[http://dx.doi.org/10.1016/S0924-8579(02)00162-0] [PMID: 12385700]
[http://dx.doi.org/10.1016/j.ijantimicag.2010.09.011] [PMID: 21075604]
[http://dx.doi.org/10.1055/s-2002-36347] [PMID: 12494348]
[http://dx.doi.org/10.1002/ptr.2695] [PMID: 19224523]
[PMID: 21589765]
[http://dx.doi.org/10.1128/AAC.00216-07] [PMID: 17664318]
[http://dx.doi.org/10.1016/j.phytochem.2006.10.001] [PMID: 17109904]
[http://dx.doi.org/10.1016/j.ijantimicag.2011.01.016] [PMID: 21411294]
[http://dx.doi.org/10.3390/molecules15117750] [PMID: 21042264]
[http://dx.doi.org/10.1093/jac/dkn178] [PMID: 18430720]
[http://dx.doi.org/10.1002/ptr.1420] [PMID: 15597311]
[http://dx.doi.org/10.1016/j.phytol.2008.01.002]
[http://dx.doi.org/10.1093/jac/dkq079] [PMID: 20304975]
[http://dx.doi.org/10.1093/jac/dkn088] [PMID: 18334493]
[PMID: 11816833]
[http://dx.doi.org/10.1099/jmm.0.47823-0] [PMID: 18566143]
[http://dx.doi.org/10.1093/trstmh/trt059] [PMID: 23843564]
[PMID: 19149076]
[http://dx.doi.org/10.1128/JCM.42.6.2701-2706.2004] [PMID: 15184455]
[http://dx.doi.org/10.1021/jm9904598] [PMID: 10585202]
[http://dx.doi.org/10.1128/AAC.44.12.3441-3443.2000] [PMID: 11083655]
[http://dx.doi.org/10.1089/10766290260469543] [PMID: 12523625]
[http://dx.doi.org/10.1128/AAC.49.2.849-852.2005] [PMID: 15673787]
[http://dx.doi.org/10.2174/138945006777709557] [PMID: 16842215]
[http://dx.doi.org/10.1128/AAC.48.3.1043-1046.2004] [PMID: 14982806]
[http://dx.doi.org/10.1006/bbrc.1999.0357] [PMID: 10080959]
[http://dx.doi.org/10.1128/AAC.00223-06] [PMID: 16954315]
[http://dx.doi.org/10.1016/j.ijantimicag.2012.01.012] [PMID: 22445204]
[http://dx.doi.org/10.1128/JB.187.14.4707-4719.2005] [PMID: 15995185]
[http://dx.doi.org/10.1016/j.ijantimicag.2007.10.025] [PMID: 18180147]
[http://dx.doi.org/10.1128/AAC.01644-07] [PMID: 18362193]
[http://dx.doi.org/10.1128/AAC.37.8.1624] [PMID: 8215274]
[http://dx.doi.org/10.1016/j.bmc.2007.04.023] [PMID: 17498961]
[http://dx.doi.org/10.1016/j.bmcl.2008.06.093] [PMID: 18632270]
[http://dx.doi.org/10.1271/bbb.100433] [PMID: 21071837]
[http://dx.doi.org/10.1128/AAC.48.11.4171-4176.2004] [PMID: 15504837]
[http://dx.doi.org/10.1164/rccm.201304-0650OC] [PMID: 23805786]
[http://dx.doi.org/10.1073/pnas.93.20.10668] [PMID: 8855237]
[http://dx.doi.org/10.1016/j.bmcl.2004.04.018] [PMID: 15149651]
[http://dx.doi.org/10.1016/S0924-8579(03)00220-6] [PMID: 13678830]
[http://dx.doi.org/10.2174/0929867013371743] [PMID: 11562289]
[http://dx.doi.org/10.2217/fmb-2019-0235] [PMID: 32073314]
[http://dx.doi.org/10.1080/13543776.2019.1618273] [PMID: 31079547]
[http://dx.doi.org/10.3390/antibiotics2010028] [PMID: 27029290]
[http://dx.doi.org/10.1093/jac/dkv316] [PMID: 26472768]
[http://dx.doi.org/10.1002/med.21591] [PMID: 31004360]
[http://dx.doi.org/10.1016/S0014-827X(01)01002-3] [PMID: 11347972]
[http://dx.doi.org/10.1038/srep18877] [PMID: 26728712]
[http://dx.doi.org/10.1080/08927014.2015.1048686] [PMID: 26057498]
[http://dx.doi.org/10.1088/0957-4484/16/9/082]
[http://dx.doi.org/10.1016/j.nano.2009.04.006] [PMID: 19447203]
[http://dx.doi.org/10.1007/s00253-015-7154-4] [PMID: 26610805]
[http://dx.doi.org/10.1002/jbm.b.31615] [PMID: 20225250]
[http://dx.doi.org/10.1002/jctb.4766]
[http://dx.doi.org/10.1021/bi100268k] [PMID: 20540528]
[http://dx.doi.org/10.1007/s40097-016-0205-2]
[http://dx.doi.org/10.1016/j.jconrel.2008.08.021] [PMID: 18822327]
[http://dx.doi.org/10.1586/eri.12.57] [PMID: 22943401]
[http://dx.doi.org/10.1017/S1462399410001766] [PMID: 21342612]
[http://dx.doi.org/10.3390/molecules25092103] [PMID: 32365898]
[http://dx.doi.org/10.1007/s12274-017-1947-y]
[http://dx.doi.org/10.1590/S1517-83822010000300006] [PMID: 24031531]
[http://dx.doi.org/10.1016/j.jep.2011.06.039] [PMID: 21782012]
[http://dx.doi.org/10.3109/00365541003713630] [PMID: 20380543]
[PMID: 12493782]
[http://dx.doi.org/10.1002/ptr.1799] [PMID: 16397919]
[http://dx.doi.org/10.1016/j.phymed.2007.01.005] [PMID: 17303397]
[http://dx.doi.org/10.1016/S0031-9422(02)00446-6] [PMID: 12475623]
[http://dx.doi.org/10.1590/S0102-695X2011005000014]
[http://dx.doi.org/10.1159/000381175] [PMID: 25999020]
[http://dx.doi.org/10.2174/0929867323666160304150522] [PMID: 26947776]
[http://dx.doi.org/10.1016/j.jpha.2019.11.002]
[http://dx.doi.org/10.1128/AAC.00730-19] [PMID: 31209007]
[PMID: 28494730]
[http://dx.doi.org/10.4103/ijmr.IJMR_2079_17] [PMID: 31219077]
[http://dx.doi.org/10.1055/s-0032-1328259] [PMID: 23468310]
[http://dx.doi.org/10.1016/j.phymed.2015.02.003] [PMID: 25925969]
[http://dx.doi.org/10.1016/j.ijantimicag.2013.08.007] [PMID: 24119569]
[http://dx.doi.org/10.1111/jphp.12315] [PMID: 25212982]
[http://dx.doi.org/10.1002/ptr.1711] [PMID: 16114093]
[http://dx.doi.org/10.1139/w05-022] [PMID: 16175202]
[http://dx.doi.org/10.1016/j.fitote.2013.07.015] [PMID: 23892000]
[http://dx.doi.org/10.1055/s-0030-1250606] [PMID: 21157683]
[http://dx.doi.org/10.2174/1573407215666190318125023]
[http://dx.doi.org/10.2174/1874842201603010075]