Optimizing the restored chemotactic behavior of anticancer agent Salmonella enterica serovar Typhimurium VNP20009

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dc.contributor.authorBroadway, Katherine M.en
dc.contributor.authorSuh, SeungBeumen
dc.contributor.authorBehkam, Baharehen
dc.contributor.authorScharf, Birgit E.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentBiomedical Engineering and Sciencesen
dc.date.accessioned2017-12-18T20:19:18Zen
dc.date.available2017-12-18T20:19:18Zen
dc.date.issued2017-06-10en
dc.description.abstractBacteria, including strains of Salmonella, have been researched and applied as therapeutic cancer agents for centuries. Salmonella are particularly of interest due to their facultative anaerobic nature, facilitating colonization of differentially oxygenated tumor regions. Additionally, Salmonella can be manipulated with relative ease, resulting in the ability to attenuate the pathogen or engineer vectors for drug delivery. It was recently discovered that the anti-cancer Salmonella enterica serovar Typhimurium strain VNP20009 is lacking in chemotactic ability, due to a non-synonymous single nucleotide polymorphism in cheY. Replacing the mutated copy of cheY with the wild-type sequence restored chemotaxis to 70% of the parental strain. We aimed to investigate further if chemotaxis of VNP20009 can be optimized. By restoring the gene msbB in VNP20009 cheY+, which confers attenuation by lipid A modification, we observed a 9% increase in swimming speed, 13% increase in swim plate performance, 19% increase in microfluidic device partitioning towards the attractant at the optimum concentration gradient, and mitigation of a non-motile cell subpopulation. We conclude that chemotaxis can be enhanced further but at the cost of changing one defining characteristic of VNP20009. A less compromised strain might be needed to employ for investigating bacterial chemotaxis in tumor interactions.en
dc.description.versionPublisheden
dc.format.extent76 - 83 (8) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.jbiotec.2017.04.006en
dc.identifier.eissn1873-4863en
dc.identifier.issn0168-1656en
dc.identifier.orcidScharf, BE [0000-0001-6271-8972]en
dc.identifier.urihttp://hdl.handle.net/10919/81271en
dc.identifier.volume251en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000402470300010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBiotechnologyen
dc.subjectBacterial anti-tumor therapyen
dc.subjectChemotaxisen
dc.subjectMicrofluidic chemotaxis assayen
dc.subjectTumor-colonizing bacteriaen
dc.subjectApplied Microbiologyen
dc.subjectSalmonellaen
dc.subjectTUMOR-GROWTHen
dc.subjectDNA VACCINEen
dc.subjectESCHERICHIA-COLIen
dc.subjectANTITUMOR AGENTen
dc.subjectApplied Microbiologyen
dc.subjectCANCER-THERAPYen
dc.subjectBREAST-CANCERen
dc.subjectMOUSE MODELSen
dc.titleOptimizing the restored chemotactic behavior of anticancer agent Salmonella enterica serovar Typhimurium VNP20009en
dc.title.serialJournal of Biotechnologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineering/Mechanical Engineeringen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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