{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:13:46Z","timestamp":1775664826587,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030B_201273"],"award-info":[{"award-number":["310030B_201273"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Bartonella<\/jats:italic>\n                    spp. are Gram-negative facultative intracellular pathogens that infect diverse mammals and cause a long-lasting intra-erythrocytic bacteremia in their natural host. These bacteria translocate\n                    <jats:italic>Bartonella<\/jats:italic>\n                    effector proteins (Beps) into host cells\n                    <jats:italic>via<\/jats:italic>\n                    their VirB\/VirD4 type 4 secretion system (T4SS) in order to subvert host cellular functions, thereby leading to the downregulation of innate immune responses. Most studies on the functional analysis of the VirB\/VirD4 T4SS and the Beps were performed with the major zoonotic pathogen\n                    <jats:italic>Bartonella henselae<\/jats:italic>\n                    for which efficient\n                    <jats:italic>in vitro<\/jats:italic>\n                    infection protocols have been established. However, its natural host, the cat, is unsuitable as an experimental infection model.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies were mostly confined to rodent models using rodent-specific\n                    <jats:italic>Bartonella<\/jats:italic>\n                    species, while the\n                    <jats:italic>in vitro<\/jats:italic>\n                    infection protocols devised for\n                    <jats:italic>B. henselae<\/jats:italic>\n                    are not transferable for those pathogens. The disparities of\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies in different species have hampered progress in our understanding of\n                    <jats:italic>Bartonella<\/jats:italic>\n                    pathogenesis. Here we describe the murine-specific strain\n                    <jats:italic>Bartonella taylorii<\/jats:italic>\n                    IBS296 as a new model organism facilitating the study of bacterial pathogenesis both\n                    <jats:italic>in vitro<\/jats:italic>\n                    in cell cultures and\n                    <jats:italic>in vivo<\/jats:italic>\n                    in laboratory mice. We implemented the split NanoLuc luciferase-based translocation assay to study BepD translocation through the VirB\/VirD4 T4SS. We found increased effector-translocation into host cells if the bacteria were grown on tryptic soy agar (TSA) plates and experienced a temperature shift immediately before infection. The improved infectivity\n                    <jats:italic>in vitro<\/jats:italic>\n                    was correlating to an upregulation of the VirB\/VirD4 T4SS. Using our adapted infection protocols, we showed BepD-dependent immunomodulatory phenotypes\n                    <jats:italic>in vitro<\/jats:italic>\n                    . In mice, the implemented growth conditions enabled infection by a massively reduced inoculum without having an impact on the course of the intra-erythrocytic bacteremia. The established model opens new avenues to study the role of the VirB\/VirD4 T4SS and the translocated Bep effectors\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2022.913434","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T10:28:23Z","timestamp":1657880903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Bartonella taylorii: A Model Organism for Studying Bartonella Infection in vitro and in vivo"],"prefix":"10.3389","volume":"13","author":[{"given":"Katja","family":"Fromm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Boegli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Ortelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Bohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Malmsheimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Dehio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1128\/JB.01972-12","article-title":"The Bartonella quintana extracytoplasmic function sigma factor RpoE has a role in bacterial adaptation to the arthropod vector environment","volume":"195","author":"Abromaitis","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/978-3-319-75241-9_2","article-title":"Structural and molecular biology of type IV secretion systems","volume":"413","author":"Berge","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7439","DOI":"10.1128\/AEM.02598-13","article-title":"Assessment of persistence of Bartonella henselae in Ctenocephalides felis","volume":"79","author":"Bouhsira","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5313","DOI":"10.1128\/iai.69.9.5313-5317.2001","article-title":"Kinetics of Bartonella birtlesii infection in experimentally infected mice and pathogenic effect on reproductive functions","volume":"69","author":"Boulouis","year":"2001","journal-title":"Infect. Immun."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1051\/vetres\/2009011","article-title":"Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors","volume":"40","author":"Chomel","year":"2009","journal-title":"Vet. Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1111\/j.1365-2672.2010.04679.x","article-title":"Bartonellosis, an increasingly recognized zoonosis","volume":"109","author":"Chomel","year":"2010","journal-title":"J. Appl. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1128\/JCM.34.8.1952-1956.1996","article-title":"Experimental transmission of Bartonella henselae by the cat flea","volume":"34","author":"Chomel","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0882-4010(87)90078-7","article-title":"Transcription of the yop regulon from Y. enterocolitica requires trans acting pYV and chromosomal genes","volume":"2","author":"Cornelis","year":"1987","journal-title":"Microb. Pathog."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1128\/MMBR.00046-09","article-title":"ppGpp conjures bacterial virulence","volume":"74","author":"Dalebroux","year":"2010","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.micpath.2016.05.007","article-title":"Identification and functional analysis of invasion associated locus B (IalB) in Bartonella species","volume":"98","author":"Deng","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/jmedent\/35.5.625","article-title":"Experimental infection of domestic cats with Bartonella henselae by inoculation of Ctenocephalides felis (Siphonaptera: Pulicidae) feces","volume":"35","author":"Foil","year":"1998","journal-title":"J. Med. Entomol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"762582","DOI":"10.3389\/fmicb.2021.762582","article-title":"The impact of Bartonella VirB\/VirD4 type IV secretion system effectors on eukaryotic host cells","volume":"12","author":"Fromm","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1128\/CMR.05009-11","article-title":"Intruders below the radar: molecular pathogenesis of Bartonella spp.","volume":"25","author":"Harms","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1093\/gbe\/evx042","article-title":"Evolutionary dynamics of pathoadaptation revealed by three independent acquisitions of the VirB\/D4 type IV secretion system in Bartonella","volume":"9","author":"Harms","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1590\/s0036-46652002000600006","article-title":"A prospective study of cat-scratch disease in Lima-Peru","volume":"44","author":"Huarcaya","year":"2002","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1128\/IAI.01584-07","article-title":"Characterization of murine dendritic cell line JAWS II and primary bone marrow-derived dendritic cells in chlamydia muridarum antigen presentation and induction of protective immunity","volume":"76","author":"Jiang","year":"2008","journal-title":"Infect. Immun."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1080\/08998280.2021.1984791","article-title":"Diagnosis and interpretation of testing for cat scratch disease","volume":"35","author":"Khalfe","year":"2022","journal-title":"Proc. (Baylor Univ. Med. Cent.)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4049\/jimmunol.167.1.11","article-title":"Cutting edge: antibody-mediated cessation of hemotropic infection by the intraerythrocytic mouse pathogen Bartonella grahamii","volume":"167","author":"Koesling","year":"2001","journal-title":"J. Immunol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.2353\/ajpath.2008.070591","article-title":"Lymphadenopathy in a novel mouse model of Bartonella-induced cat scratch disease results from lymphocyte immigration and proliferation and is regulated by interferon-alpha\/beta","volume":"172","author":"Kunz","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"852","DOI":"10.4161\/21505594.2014.970949","article-title":"Thermal control of virulence factors in bacteria: a hot topic","volume":"5","author":"Lam","year":"2014","journal-title":"Virulence"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"7981","DOI":"10.1128\/AEM.02041-15","article-title":"High prevalence and genetic heterogeneity of rodent-borne Bartonella species on Heixiazi Island, China","volume":"81","author":"Li","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1111\/cmi.12070","article-title":"Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB\/D4 type IV secretion system","volume":"15","author":"Lu","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref23","article-title":"Bartonellosis","volume-title":"StatPearls","author":"Mada","year":"2022"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.clindermatol.2008.10.006","article-title":"Bartonellosis","volume":"27","author":"Maguina","year":"2009","journal-title":"Clin. Dermatol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e1008548","DOI":"10.1371\/journal.ppat.1008548","article-title":"Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane","volume":"17","author":"Marlaire","year":"2021","journal-title":"PLoS Pathog."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5735","DOI":"10.1128\/IAI.73.9.5735-5742.2005","article-title":"Interaction of Bartonella henselae with endothelial cells promotes monocyte\/macrophage chemoattractant protein 1 gene expression and protein production and triggers monocyte migration","volume":"73","author":"McCord","year":"2005","journal-title":"Infect. Immun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"5974","DOI":"10.1128\/IAI.69.10.5974-5980.2001","article-title":"Interaction of Bartonella henselae with the murine macrophage cell line J774: infection and proinflammatory response","volume":"69","author":"Musso","year":"2001","journal-title":"Infect. Immun."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e1004187","DOI":"10.1371\/journal.ppat.1004187","article-title":"A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors","volume":"10","author":"Okujava","year":"2014","journal-title":"PLoS Pathog."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1016\/j.jmb.2019.03.007","article-title":"A high-resolution luminescent assay for rapid and continuous monitoring of protein translocation across biological membranes","volume":"431","author":"Pereira","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/s0923-2508(97)83619-4","article-title":"A role for H-NS in the regulation of the virF gene of Shigella and enteroinvasive Escherichia coli","volume":"149","author":"Prosseda","year":"1998","journal-title":"Res. Microbiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1128\/JB.01676-09","article-title":"The BatR\/BatS two-component regulatory system controls the adaptive response of Bartonella henselae during human endothelial cell infection","volume":"192","author":"Quebatte","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1111\/mmi.12396","article-title":"Dual input control: activation of the Bartonella henselae VirB\/D4 type IV secretion system by the stringent sigma factor RpoH1 and the BatR\/BatS two-component system","volume":"90","author":"Quebatte","year":"2013","journal-title":"Mol. Microbiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/0092-8674(78)90101-0","article-title":"Functional macrophage cell lines transformed by Abelson leukemia virus","volume":"15","author":"Raschke","year":"1978","journal-title":"Cell"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5534","DOI":"10.1128\/IAI.66.11.5534-5536.1998","article-title":"Murine model of Bartonella henselae infection in the immunocompetent host","volume":"66","author":"Regnath","year":"1998","journal-title":"Infect. Immun."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1084\/jem.20040500","article-title":"Bartonella adhesin a mediates a proangiogenic host cell response","volume":"200","author":"Riess","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.1016\/j.bbamcr.2017.09.008","article-title":"Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling","volume":"1864","author":"Rouault","year":"2017","journal-title":"Biochim. Biophys. Acta, Mol. Cell Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s00109-005-0014-4","article-title":"Autophagy in innate and adaptive immunity against intracellular pathogens","volume":"84","author":"Schmid","year":"","journal-title":"J. Mol. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e115","DOI":"10.1371\/journal.ppat.0020115","article-title":"A translocated bacterial protein protects vascular endothelial cells from apoptosis","volume":"2","author":"Schmid","year":"","journal-title":"PLoS Pathog."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1046\/j.1365-2958.2002.03208.x","article-title":"The VirB\/VirD4 type IV secretion system of Bartonella is essential for establishing intraerythrocytic infection","volume":"46","author":"Schulein","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1073\/pnas.0406796102","article-title":"A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells","volume":"102","author":"Schulein","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1078\/1438-4221-00167","article-title":"Bacterial persistence within erythrocytes: a unique pathogenic strategy of Bartonella spp.","volume":"291","author":"Seubert","year":"2002","journal-title":"Int. J. Med. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e00238","DOI":"10.1128\/mBio.00238-12","article-title":"Thermal control of microbial development and virulence: molecular mechanisms of microbial temperature sensing","volume":"3","author":"Shapiro","year":"2012","journal-title":"mBio"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e2202059119","DOI":"10.1073\/pnas.2202059119","article-title":"Identification of the Bartonella autotransporter CFA as a protective antigen and hypervariable target of neutralizing antibodies in mice","volume":"119","author":"Siewert","year":"2022","journal-title":"PNAS"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"476.e7","DOI":"10.1016\/j.chom.2020.01.015","article-title":"A Bartonella effector acts as signaling hub for intrinsic STAT3 activation to trigger anti-inflammatory responses","volume":"27","author":"Sorg","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12879-019-3929-z","article-title":"First isolation and genotyping of Bartonella henselae from a cat living with a patient with cat scratch disease in Southeast Europe","volume":"19","author":"Stepanic","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.micpath.2015.12.010","article-title":"Characterization of the general stress response in Bartonella henselae","volume":"92","author":"Tu","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e1000946","DOI":"10.1371\/journal.ppat.1000946","article-title":"The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes","volume":"6","author":"Vayssier-Taussat","year":"2010","journal-title":"PLoS Pathog."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1073\/pnas.0406241102","article-title":"Positive charge is an important feature of the C-terminal transport signal of the VirB\/D4-translocated proteins of agrobacterium","volume":"102","author":"Vergunst","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e13004","DOI":"10.1111\/cmi.13004","article-title":"Role of distinct type-IV-secretion systems and secreted effector sets in host adaptation by pathogenic Bartonella species","volume":"21","author":"Wagner","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"921","DOI":"10.3389\/fmicb.2019.00921","article-title":"Versatility of the BID domain: conserved function as type-IV-secretion-signal and secondarily evolved effector functions within Bartonella-infected host cells","volume":"10","author":"Wagner","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e47012","DOI":"10.15252\/embr.201847012","article-title":"From conjugation to T4S systems in gram-negative bacteria: a mechanistic biology perspective","volume":"20","author":"Waksman","year":"2019","journal-title":"EMBO Rep."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"e12984","DOI":"10.1111\/cmi.12984","article-title":"Bartonella quintana type IV secretion effector BepE-induced selective autophagy by conjugation with K63 polyubiquitin chain","volume":"21","author":"Wang","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"E5776","DOI":"10.1073\/pnas.1804668115","article-title":"ABC transporter content diversity in Streptococcus pneumoniae impacts competence regulation and bacteriocin production","volume":"115","author":"Wang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1111\/mmi.14490","article-title":"A NanoLuc luciferase-based assay enabling the real-time analysis of protein secretion and injection by bacterial type III secretion systems","volume":"113","author":"Westerhausen","year":"2020","journal-title":"Mol. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.913434\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T10:28:27Z","timestamp":1657880907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.913434\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":54,"alternative-id":["10.3389\/fmicb.2022.913434"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.913434","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.03.11.483615","asserted-by":"object"}]},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]},"article-number":"913434"}}