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During the natural enzootic life cycle of Borrelia burgdorferi (also known as Borreliella burgdorferi ), the bacteria must sense conditions within the vertebrate and arthropod and appropriately regulate expression of genes necessary to persist within these distinct environments. bb0345 of B. burgdorferi encodes a hypothetical protein of unknown function that is predicted to contain an N-terminal helix-turn-helix (HTH) domain. Because HTH domains can mediate protein-DNA interactions, we hypothesized that BB0345 might represent a previously unidentified borrelial transcriptional regulator with the ability to regulate events critical for the B. burgdorferi enzootic cycle. To study the role of BB0345 within mammals, we generated a bb0345 mutant and assessed its virulence potential in immunocompetent mice. The bb0345 mutant was able to initiate localized infection and disseminate to distal tissues but was cleared from all sites by 14 days postinfection. In vitro growth curve analyses revealed that the bb0345 mutant grew similar to wild-type bacteria in standard Barbour-Stoenner-Kelley II (BSK-II) medium; however, the mutant was not able to grow in dilute BSK-II medium or dialysis membrane chambers (DMCs) implanted in rats. Proteinase K accessibility assays and whole-cell partitioning indicated that BB0345 was intracellular and partially membrane associated. Comparison of protein production profiles between the wild-type parent and the bb0345 mutant revealed no major differences, suggesting BB0345 may not be a global transcriptional regulator. Taken together, these data show that BB0345 is essential for B. burgdorferi survival in the mammalian host, potentially by aiding the spirochete with a physiological function that is required by the bacterium during infection.

Titel:	The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection.
Autor/in / Beteiligte Person:	Graham, DE ; Groshong, AM ; Jackson-Litteken, CD ; Moore, BP ; Caimano, MJ ; Blevins, JS
Link:	Full Text Finder (Volltext)
Zeitschrift:	Infection and immunity, Jg. 88 (2020-11-16), Heft 12
Veröffentlichung:	Washington, DC : American Society For Microbiology ; <i>Original Publication</i>: [Bethesda, Md.] American Society for Microbiology., 2020
Medientyp:	academicJournal
ISSN:	1098-5522 (electronic)
DOI:	10.1128/IAI.00472-20
Schlagwort:	Animals Bacterial Proteins chemistry Bacterial Proteins genetics Borrelia burgdorferi genetics Borrelia burgdorferi growth & development Borrelia burgdorferi pathogenicity Computational Biology Female Lipoproteins chemistry Lipoproteins genetics Membrane Proteins genetics Membrane Proteins metabolism Mice Rats Rats, Sprague-Dawley Recombinant Proteins Spirochaetales genetics Spirochaetales metabolism Spirochaetales pathogenicity Bacterial Proteins metabolism Borrelia burgdorferi metabolism Gene Expression Regulation, Bacterial genetics Host Microbial Interactions genetics Lipoproteins metabolism Lyme Disease microbiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Infect Immun] 2020 Nov 16; Vol. 88 (12). <i>Date of Electronic Publication: </i>2020 Nov 16 (<i>Print Publication: </i>2020). MeSH Terms: Bacterial Proteins / metabolism ; Borrelia burgdorferi / metabolism ; Gene Expression Regulation, Bacterial / genetics ; Host Microbial Interactions / genetics ; Lipoproteins / metabolism ; Lyme Disease / microbiology ; Animals ; Bacterial Proteins / chemistry ; Bacterial Proteins / genetics ; Borrelia burgdorferi / genetics ; Borrelia burgdorferi / growth & development ; Borrelia burgdorferi / pathogenicity ; Computational Biology ; Female ; Lipoproteins / chemistry ; Lipoproteins / genetics ; Membrane Proteins / genetics ; Membrane Proteins / metabolism ; Mice ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; Spirochaetales / genetics ; Spirochaetales / metabolism ; Spirochaetales / pathogenicity References: Nature. 1997 Dec 11;390(6660):580-6. (PMID: 9403685) ; PLoS One. 2016 Oct 5;11(10):e0164165. (PMID: 27706236) ; J Bacteriol. 2017 Feb 28;199(6):. (PMID: 28069820) ; PLoS One. 2009 Oct 19;4(10):e7526. (PMID: 19838305) ; Infect Immun. 2010 Jan;78(1):265-74. 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(PMID: 14722614) Grant Information: R21 AI126146 United States AI NIAID NIH HHS; R25 GM083247 United States GM NIGMS NIH HHS; R21 AI119532 United States AI NIAID NIH HHS; R01 AI029735 United States AI NIAID NIH HHS; R01 AI087678 United States AI NIAID NIH HHS; P20 GM103625 United States GM NIGMS NIH HHS Contributed Indexing: Keywords: Borrelia; Borrelia burgdorferi; Borreliella; Lyme disease; molecular genetics; pathogenesis; spirochetes Substance Nomenclature: 0 (BB0365 protein, Borrelia burgdorferi) ; 0 (Bacterial Proteins) ; 0 (Lipoproteins) ; 0 (Membrane Proteins) ; 0 (Recombinant Proteins) Entry Date(s): Date Created: 20200915 Date Completed: 20210519 Latest Revision: 20210723 Update Code: 20240513 PubMed Central ID: PMC7671889

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The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection.