Abstract
Bacterial Persister Cells (BPCs) are quiescent, slow-growing or growth-arrested phenotypic variants of normal bacterial cells that are transiently tolerant to antibiotics. It seems that persister cells are the main cause of the recurrence of various chronic infections. Stress response (RpoS-mediated), Toxin-Antitoxin (TA) systems, inhibition of ATP production, Reactive Oxygen Species (ROS), efflux pumps, bacterial SOS response, cell-to-cell communication and stringent response (ppGpp- mediated) are the primary potential mechanisms for persistence cell formation. However, eradicating persistent cells is challenging as the specific molecular mechanisms that initiate their formation remain fuzzy and unknown. Here we reviewed and summarized the current understanding of how bacterial persister cells are formed, controlled, and destroyed.
Graphical Abstract
[http://dx.doi.org/10.1016/j.micpath.2021.104998] [PMID: 34044041]
[http://dx.doi.org/10.1016/j.micpath.2020.104585] [PMID: 33075520]
[http://dx.doi.org/10.1080/14760584.2018.1488590] [PMID: 29902092]
[http://dx.doi.org/10.1038/nrmicro1557] [PMID: 17143318]
[http://dx.doi.org/10.3181/00379727-50-13773]
[http://dx.doi.org/10.1016/S0140-6736(00)74210-3]
[http://dx.doi.org/10.1128/AAC.06288-11] [PMID: 22391538]
[http://dx.doi.org/10.1007/978-3-540-75418-3_6]
[http://dx.doi.org/10.1128/AAC.49.4.1483-1494.2005] [PMID: 15793130]
[http://dx.doi.org/10.1146/annurev.micro.112408.134306] [PMID: 20528688]
[http://dx.doi.org/10.3390/antibiotics10010003] [PMID: 33374551]
[http://dx.doi.org/10.1128/JB.188.10.3494-3497.2006] [PMID: 16672603]
[http://dx.doi.org/10.1038/msb4100050] [PMID: 16738554]
[http://dx.doi.org/10.1038/nrmicro1743] [PMID: 17694072]
[http://dx.doi.org/10.1038/239500a0] [PMID: 4563019]
[http://dx.doi.org/10.1016/j.bbrc.2020.01.102] [PMID: 32007277]
[PMID: 31957618]
[http://dx.doi.org/10.1126/science.1163806] [PMID: 19150849]
[http://dx.doi.org/10.1371/journal.pbio.1000317] [PMID: 20186264]
[http://dx.doi.org/10.1126/science.aaf4268] [PMID: 27980159]
[http://dx.doi.org/10.1016/j.cell.2014.02.050] [PMID: 24766804]
[http://dx.doi.org/10.3389/fmicb.2017.00191] [PMID: 28261163]
[http://dx.doi.org/10.1128/mBio.02267-16] [PMID: 28174313]
[http://dx.doi.org/10.1126/science.1244705] [PMID: 24408438]
[http://dx.doi.org/10.1038/srep38204] [PMID: 27910884]
[http://dx.doi.org/10.1111/1462-2920.12567] [PMID: 25041421]
[http://dx.doi.org/10.1042/BJ20140073] [PMID: 24502667]
[http://dx.doi.org/10.1046/j.1365-2958.2003.03512.x] [PMID: 12787364]
[http://dx.doi.org/10.1016/S0022-2836(03)00922-7] [PMID: 12972253]
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a003313] [PMID: 12473202]
[http://dx.doi.org/10.1371/journal.ppat.1002121] [PMID: 21829345]
[http://dx.doi.org/10.1126/science.1061315] [PMID: 11474114]
[http://dx.doi.org/10.1016/j.femsle.2004.11.005] [PMID: 15621433]
[http://dx.doi.org/10.1111/j.1751-7915.2011.00327.x] [PMID: 22221537]
[http://dx.doi.org/10.3389/fmicb.2015.01003] [PMID: 26483762]
[http://dx.doi.org/10.3389/fmicb.2017.01795] [PMID: 28979246]
[http://dx.doi.org/10.1128/JB.02210-12] [PMID: 23667235]
[http://dx.doi.org/10.1371/journal.pgen.1000760] [PMID: 20011100]
[http://dx.doi.org/10.1128/AAC.01218-09] [PMID: 20086164]
[http://dx.doi.org/10.1128/JB.00369-06] [PMID: 16816185]
[http://dx.doi.org/10.1128/jb.176.7.1977-1984.1994] [PMID: 8144465]
[http://dx.doi.org/10.1126/science.284.5418.1318] [PMID: 10334980]
[http://dx.doi.org/10.1128/JB.01237-06] [PMID: 17041039]
[http://dx.doi.org/10.1038/nbt1126] [PMID: 16151404]
[http://dx.doi.org/10.1111/j.1574-6968.2009.01657.x] [PMID: 19508279]
[http://dx.doi.org/10.1128/jb.155.2.768-775.1983] [PMID: 6348026]
[http://dx.doi.org/10.1128/AAC.00144-08] [PMID: 18519731]
[http://dx.doi.org/10.1016/j.resmic.2006.05.004] [PMID: 16854568]
[http://dx.doi.org/10.1016/j.molcel.2013.08.045] [PMID: 24095282]
[http://dx.doi.org/10.1073/pnas.0507850102] [PMID: 16227431]
[http://dx.doi.org/10.1128/JB.01285-09] [PMID: 20061486]
[http://dx.doi.org/10.1016/j.drup.2018.03.002] [PMID: 29857815]
[http://dx.doi.org/10.1016/j.micpath.2020.104393] [PMID: 32711113]
[http://dx.doi.org/10.1111/1751-7915.12774] [PMID: 28696066]
[http://dx.doi.org/10.1002/bit.25721] [PMID: 26264116]
[http://dx.doi.org/10.1111/1462-2920.12873] [PMID: 25858802]
[http://dx.doi.org/10.1128/AAC.00864-15] [PMID: 26014929]
[http://dx.doi.org/10.2217/fmb-2016-0064] [PMID: 27546386]
[http://dx.doi.org/10.1038/nature12790] [PMID: 24226776]
[http://dx.doi.org/10.1038/nature12790] [PMID: 24226776]
[http://dx.doi.org/10.4155/fmc.15.189] [PMID: 26910612]
[http://dx.doi.org/10.3389/fmicb.2015.00641] [PMID: 26157437]
[http://dx.doi.org/10.1371/journal.pone.0117207] [PMID: 25806811]
[http://dx.doi.org/10.1128/AEM.02440-10] [PMID: 21622798]
[http://dx.doi.org/10.1007/s00253-015-6645-7] [PMID: 26012420]
[http://dx.doi.org/10.1128/AEM.01576-14] [PMID: 25192989]
[http://dx.doi.org/10.1128/AAC.00708-11] [PMID: 21844322]
[http://dx.doi.org/10.3389/fmicb.2019.02028] [PMID: 31551965]
[http://dx.doi.org/10.1371/journal.pone.0085998] [PMID: 24523858]
[http://dx.doi.org/10.3389/fmicb.2018.01724] [PMID: 30123191]
[http://dx.doi.org/10.1093/infdis/jiu286] [PMID: 24837402]
[http://dx.doi.org/10.1038/nature10069] [PMID: 21562562]
[http://dx.doi.org/10.1126/scitranslmed.3006276] [PMID: 23785037]
[http://dx.doi.org/10.1038/ncomms10750] [PMID: 26892159]
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.02.003] [PMID: 26849946]
[http://dx.doi.org/10.1097/MRM.0000000000000216]
[http://dx.doi.org/10.1186/s12866-019-1506-7] [PMID: 31234796]
[http://dx.doi.org/10.1016/j.bmc.2010.04.064] [PMID: 20483622]
[http://dx.doi.org/10.3389/fmicb.2017.00924] [PMID: 28596760]
[http://dx.doi.org/10.1002/bit.25963] [PMID: 26914280]
[http://dx.doi.org/10.1371/journal.pone.0084220] [PMID: 24349568]
[http://dx.doi.org/10.1371/journal.pone.0127640] [PMID: 26039584]
[http://dx.doi.org/10.1073/pnas.1203735109] [PMID: 22778419]
[http://dx.doi.org/10.1371/journal.pmed.0040344] [PMID: 18092886]
[http://dx.doi.org/10.1128/AAC.05293-11] [PMID: 21930883]
[http://dx.doi.org/10.1126/science.1208813] [PMID: 21835980]
[http://dx.doi.org/10.1128/mBio.02022-16] [PMID: 28196957]
[http://dx.doi.org/10.1038/ncomms8983] [PMID: 26246187]
[http://dx.doi.org/10.1073/pnas.1704376114] [PMID: 28396391]
[http://dx.doi.org/10.1128/AAC.01751-09] [PMID: 20855735]
[http://dx.doi.org/10.1093/jac/dkz034] [PMID: 30759206]
[http://dx.doi.org/10.1556/1886.2015.00031] [PMID: 26716015]
[http://dx.doi.org/10.2217/fmb-2019-0051] [PMID: 31271063]
[http://dx.doi.org/10.1016/j.ijantimicag.2018.11.004] [PMID: 30423343]
[http://dx.doi.org/10.1128/AAC.00987-17] [PMID: 28923873]
[http://dx.doi.org/10.1016/j.colsurfb.2020.110825] [PMID: 32006909]
[http://dx.doi.org/10.1101/312736]
[http://dx.doi.org/10.1111/php.12843] [PMID: 28881420]
[http://dx.doi.org/10.3389/fmicb.2017.01917] [PMID: 29046671]
[http://dx.doi.org/10.1002/cbic.201600622] [PMID: 27925693]
[http://dx.doi.org/10.1128/AAC.00285-16] [PMID: 27021321]
[http://dx.doi.org/10.1371/journal.ppat.1004321] [PMID: 25144274]
[http://dx.doi.org/10.1371/journal.pone.0183263] [PMID: 28837596]
[http://dx.doi.org/10.1038/srep17315] [PMID: 26616387]
[http://dx.doi.org/10.1038/srep14247] [PMID: 26435063]
[http://dx.doi.org/10.1128/AAC.01872-16] [PMID: 27736755]
[http://dx.doi.org/10.1016/j.pupt.2019.101884] [PMID: 31887372]
[http://dx.doi.org/10.1128/AAC.01481-16] [PMID: 27600051]
[http://dx.doi.org/10.1128/AAC.02136-13] [PMID: 24342644]
[http://dx.doi.org/10.2217/fmb-2015-0015] [PMID: 27158932]
[http://dx.doi.org/10.3389/fmed.2017.00169] [PMID: 29075628]
[http://dx.doi.org/10.1016/j.chembiol.2014.01.014] [PMID: 24684906]
[http://dx.doi.org/10.1016/j.chom.2008.02.003] [PMID: 18329613]
[http://dx.doi.org/10.3389/fmicb.2016.00199] [PMID: 26941723]
[http://dx.doi.org/10.1128/AAC.49.6.2294-2301.2005] [PMID: 15917524]
[http://dx.doi.org/10.1126/science.1164571] [PMID: 19039139]
[http://dx.doi.org/10.1073/pnas.1309171110] [PMID: 23776209]
[http://dx.doi.org/10.1128/mBio.03239-19] [PMID: 32047133]
[http://dx.doi.org/10.1038/s41557-019-0378-7] [PMID: 31844194]
[http://dx.doi.org/10.1128/mBio.01140-20] [PMID: 32605985]
[PMID: 32801796]
[http://dx.doi.org/10.1016/j.ejmech.2019.112026] [PMID: 31918072]
[http://dx.doi.org/10.1038/s41598-019-54212-z] [PMID: 31784584]