Abstract
Bacterial engineering modifies bacteria's genomic sequence using genetic engineering tools. These engineered bacteria can produce modified proteins, peptides, nucleic acids, and other biomolecules that can be used to treat various medical conditions. Engineered bacteria can target diseased tissues or organs, detect specific biomarkers in the diseased environment, and even induce specific conditions. Furthermore, a meticulously designed intracellular metabolic pathway can activate or inhibit the expression of related genes, synthesise biologically active therapeutic molecules, and precisely deliver drug payloads to diseased tissues or organs. Lactococcus (L. lactis), Salmonella (S. typhi), and E. coli (E. coli Nissle) are the most studied engineered microorganisms used as drug carriers. These have been used in vaccines to treat multifactorial diseases such as cancer, autoimmune diseases, metabolic diseases, and inflammatory conditions. Other promising strains include Bifidobacterium animalis, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus lugdunensis, and Clostridium sporogenes. Despite the low reported risk, toxic effects associated with bacterial cells, limiting their efficacy and rapid clearance due to immune responses stimulated by high bacterial concentrations, remain major drawbacks. As a result, a better and more effective method of drug delivery must be developed by combining bacterial-based therapies with other available treatments, and more research in this area is also needed.
Graphical Abstract
[http://dx.doi.org/10.1038/nrmicro929] [PMID: 15197394]
[http://dx.doi.org/10.1016/j.mib.2020.07.014] [PMID: 32828048]
[http://dx.doi.org/10.1038/nrmicro2392] [PMID: 20514043]
[http://dx.doi.org/10.1016/j.addr.2016.09.007] [PMID: 27641944]
[http://dx.doi.org/10.1007/s40199-019-00291-2] [PMID: 31376116]
[http://dx.doi.org/10.1016/B978-0-12-384947-2.00356-1]
[http://dx.doi.org/10.1007/BF03194657] [PMID: 17272861]
[http://dx.doi.org/10.1007/s10295-011-1082-9] [PMID: 22252444]
[http://dx.doi.org/10.1016/j.tibtech.2006.09.001] [PMID: 16971006]
[http://dx.doi.org/10.1007/s00253-019-09628-y] [PMID: 30656391]
[http://dx.doi.org/10.1016/j.ijmm.2005.12.015] [PMID: 16446113]
[http://dx.doi.org/10.1038/nature02759] [PMID: 15241422]
[http://dx.doi.org/10.1016/S0140-6736(10)61265-2] [PMID: 21227500]
[http://dx.doi.org/10.1146/annurev.med.58.070605.115320] [PMID: 17059365]
[http://dx.doi.org/10.1007/s00253-013-4926-6] [PMID: 23644748]
[http://dx.doi.org/10.1111/j.1742-4658.2011.08182.x] [PMID: 21585657]
[http://dx.doi.org/10.1038/sj.cgt.7701003] [PMID: 17068487]
[http://dx.doi.org/10.1038/ncomms15028] [PMID: 28398304]
[http://dx.doi.org/10.1016/j.copbio.2015.05.004] [PMID: 26070111]
[http://dx.doi.org/10.2174/1566523034578357] [PMID: 12762480]
[http://dx.doi.org/10.1002/advs.202003572] [PMID: 33854892]
[http://dx.doi.org/10.1111/jam.13446] [PMID: 28295939]
[http://dx.doi.org/10.1007/978-1-4419-1132-2_12]
[http://dx.doi.org/10.1016/j.jsps.2017.12.006] [PMID: 30166921]
[http://dx.doi.org/10.15562/tcp.11]
[http://dx.doi.org/10.1016/j.addr.2005.01.027] [PMID: 15878634]
[http://dx.doi.org/10.1016/0168-1656(95)00123-9] [PMID: 8717400]
[http://dx.doi.org/10.4161/bbug.1.5.12540] [PMID: 21326832]
[http://dx.doi.org/10.1016/S0168-3659(02)00267-5] [PMID: 12480307]
[http://dx.doi.org/10.1111/j.1574-6968.1999.tb13524.x] [PMID: 10227165]
[http://dx.doi.org/10.1016/j.mimet.2021.106208] [PMID: 33766606]
[http://dx.doi.org/10.1089/fpd.2016.2184] [PMID: 27982711]
[http://dx.doi.org/10.1016/0300-9084(90)90145-7] [PMID: 2143087]
[http://dx.doi.org/10.1007/BF00248685] [PMID: 1534215]
[http://dx.doi.org/10.1111/j.1574-6976.1995.tb00203.x] [PMID: 7669347]
[http://dx.doi.org/10.1002/bit.10610] [PMID: 12673762]
[http://dx.doi.org/10.1002/bit.20014] [PMID: 14760686]
[http://dx.doi.org/10.1002/eji.1830171210] [PMID: 3500861]
[http://dx.doi.org/10.1016/j.ymben.2007.10.003] [PMID: 18164227]
[http://dx.doi.org/10.1002/bit.22542] [PMID: 19777583]
[http://dx.doi.org/10.1186/s12934-015-0313-6] [PMID: 26377321]
[http://dx.doi.org/10.1053/j.gastro.2007.04.073] [PMID: 17681173]
[http://dx.doi.org/10.3892/ol.2013.1743] [PMID: 24396491]
[http://dx.doi.org/10.7150/jca.13566] [PMID: 26918060]
[http://dx.doi.org/10.1016/j.molmet.2016.06.006] [PMID: 27656410]
[http://dx.doi.org/10.1371/journal.pone.0162733] [PMID: 27610615]
[http://dx.doi.org/10.5114/fn.2016.62534] [PMID: 27764517]
[PMID: 23210237]
[http://dx.doi.org/10.1016/j.cell.2014.03.011] [PMID: 24679531]
[http://dx.doi.org/10.1001/jama.1992.03490240060037] [PMID: 1460735]
[http://dx.doi.org/10.1001/jama.1993.03500140081040] [PMID: 8459516]
[PMID: 8867865]
[PMID: 14115686]
[http://dx.doi.org/10.1016/S1470-2045(03)01194-X] [PMID: 12965276]
[http://dx.doi.org/10.1021/sb500258b] [PMID: 25079685]
[http://dx.doi.org/10.1016/j.trecan.2020.11.004] [PMID: 33303401]
[http://dx.doi.org/10.1186/1423-0127-17-21] [PMID: 20331869]
[http://dx.doi.org/10.1038/nrc2934] [PMID: 20944664]
[http://dx.doi.org/10.1016/j.cyto.2016.01.002] [PMID: 26778055]
[http://dx.doi.org/10.1016/j.phrs.2016.10.016] [PMID: 27771464]
[http://dx.doi.org/10.1038/mt.2009.295] [PMID: 20051939]
[http://dx.doi.org/10.1038/s41467-020-16602-0] [PMID: 32483165]
[http://dx.doi.org/10.1038/s12276-018-0191-1] [PMID: 30546008]
[http://dx.doi.org/10.1002/advs.201903394] [PMID: 32328428]
[http://dx.doi.org/10.1056/NEJMra1703481] [PMID: 29320654]
[http://dx.doi.org/10.1126/scitranslmed.aax0876]
[http://dx.doi.org/10.4049/jimmunol.1601999] [PMID: 28615418]
[http://dx.doi.org/10.1016/j.celrep.2019.09.089] [PMID: 31618645]
[http://dx.doi.org/10.1126/science.aad1067]
[http://dx.doi.org/10.1146/annurev-biophys-070816-033903] [PMID: 29547341]
[http://dx.doi.org/10.1073/pnas.0701959104] [PMID: 17652173]
[http://dx.doi.org/10.1038/cgt.2008.48] [PMID: 18654612]
[http://dx.doi.org/10.1093/toxsci/kfi316] [PMID: 16162850]
[http://dx.doi.org/10.1006/anae.1998.0161] [PMID: 16887640]
[http://dx.doi.org/10.1038/s41568-018-0070-z] [PMID: 30405213]
[http://dx.doi.org/10.1016/S0168-9525(99)01950-2] [PMID: 10729833]
[http://dx.doi.org/10.1073/pnas.251543698] [PMID: 11724950]
[http://dx.doi.org/10.1021/acsabm.0c01286] [PMID: 35019596]
[http://dx.doi.org/10.1038/5205] [PMID: 9920266]
[http://dx.doi.org/10.1002/jcb.22078] [PMID: 19199339]
[http://dx.doi.org/10.1016/j.urology.2014.05.020] [PMID: 25123427]
[http://dx.doi.org/10.1038/sj.bjc.6605403] [PMID: 19861961]
[http://dx.doi.org/10.1038/cgt.2009.7] [PMID: 19229287]
[http://dx.doi.org/10.1126/science.1130651]
[http://dx.doi.org/10.18632/oncotarget.17197] [PMID: 28473665]
[http://dx.doi.org/10.1016/j.tibtech.2018.09.005] [PMID: 30318171]
[http://dx.doi.org/10.1038/srep30591] [PMID: 27464652]
[http://dx.doi.org/10.1006/anae.1999.0191] [PMID: 16887662]
[PMID: 11529249]
[http://dx.doi.org/10.1002/bit.23095] [PMID: 21337329]
[http://dx.doi.org/10.1097/MRM.0000000000000005]
[http://dx.doi.org/10.1186/1479-0556-7-4] [PMID: 19208231]
[http://dx.doi.org/10.1038/nature06005] [PMID: 17653185]
[http://dx.doi.org/10.1186/1475-2859-12-71] [PMID: 23876056]
[http://dx.doi.org/10.1126/science.289.5483.1352]
[http://dx.doi.org/10.1016/j.cgh.2006.03.028] [PMID: 16716759]
[http://dx.doi.org/10.1146/annurev-biochem-063011-092449] [PMID: 23495938]
[http://dx.doi.org/10.1038/mi.2009.116] [PMID: 19794409]
[http://dx.doi.org/10.1016/j.oraloncology.2010.04.008] [PMID: 20542722]
[http://dx.doi.org/10.1038/nbt.3879] [PMID: 28553941]
[http://dx.doi.org/10.1172/JCI72517] [PMID: 24960158]
[http://dx.doi.org/10.2337/db14-0635] [PMID: 25626737]
[http://dx.doi.org/10.1111/1751-7915.12778] [PMID: 28696008]
[http://dx.doi.org/10.3389/fcimb.2021.595575] [PMID: 33732656]
[http://dx.doi.org/10.1186/s12934-020-01350-z] [PMID: 32334588]
[http://dx.doi.org/10.1016/j.drup.2016.06.002] [PMID: 27449598]
[http://dx.doi.org/10.1016/j.copbio.2012.03.004] [PMID: 22459613]
[http://dx.doi.org/10.1128/IAI.68.2.543-549.2000]
[http://dx.doi.org/10.1007/s10534-010-9298-0] [PMID: 20148305]
[http://dx.doi.org/10.1002/adma.202102580] [PMID: 34347325]
[http://dx.doi.org/10.1086/508747] [PMID: 17083044]
[http://dx.doi.org/10.1038/mi.2011.30] [PMID: 21734653]
[http://dx.doi.org/10.1021/sb4000367] [PMID: 23808914]
[http://dx.doi.org/10.1038/nature18930] [PMID: 27437587]
[http://dx.doi.org/10.1371/journal.pone.0094051] [PMID: 24714362]
[http://dx.doi.org/10.1016/j.vaccine.2016.09.060] [PMID: 27742220]
[http://dx.doi.org/10.1111/jam.13353] [PMID: 27860045]
[http://dx.doi.org/10.1155/2013/316926] [PMID: 23766929]
[http://dx.doi.org/10.21873/anticanres.11218] [PMID: 27919942]
[http://dx.doi.org/10.1136/gutjnl-2020-322630] [PMID: 33106354]
[http://dx.doi.org/10.1007/s00253-015-6495-3] [PMID: 25794874]
[http://dx.doi.org/10.1016/j.tim.2012.05.008] [PMID: 22748513]
[PMID: 13240693]
[http://dx.doi.org/10.1038/nchembio.1979] [PMID: 26641934]
[http://dx.doi.org/10.1038/s41586-018-0092-4] [PMID: 29743671]
[http://dx.doi.org/10.1021/acssynbio.0c00497] [PMID: 33331760]
[http://dx.doi.org/10.3920/BM2012.0039] [PMID: 23257018]
[http://dx.doi.org/10.1038/509269a] [PMID: 24828169]
[http://dx.doi.org/10.1126/science.1104635]