Strain-dependent arthritogenic potential of the zoonotic pathogen Corynebacterium ulcerans

Dias, André Alves; Silva, F.C.; Santos, Louisy Sanches dos; Ribeiro-Carvalho, Marilza Moura; Sabbadini, Priscila Soares; Santos, Cíntia Silva; Filardy, Alessandra A.; Myioshi, Anderson; Azevedo, Vasco; Hirata, Raphael; Villas-Bôas, Maria Helena Simões; Mattos‐Guaraldi, Ana Luíza

doi:10.1016/j.vetmic.2011.06.007

Cited by 25 publications

(18 citation statements)

References 31 publications

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“…Based on these genome sequences and comparative genomics approaches, a number of putative virulence factors were annotated; however, functional data were scarce. Up to now, data on fibrinogen, fibronectin and collagen binding, antimicrobial profiles, and arthritogenic potential of isolates have been published (Dias et al, 2011;Simpson-Louredo et al, 2014). In the study presented here, C. ulcerans 809 and BR-AD22 were characterized for the first time to the best of our knowledge with respect to adhesion to epithelial cells, invasion of epithelial cells and the function of two putative virulence factors in these initial processes of infection.…”

Section: Introductionmentioning

confidence: 92%

Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources

et al. 2015

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Corynebacterium ulcerans is an emerging pathogen transmitted by a zoonotic pathway to humans. Despite rising numbers of infections and potentially fatal outcomes, data on the colonization of the human host are lacking up to now. In this study, adhesion of two C. ulcerans isolates to human epithelial cells, invasion of host cells and the function of two putative virulence factors with respect to these processes were investigated. C. ulcerans strains BR-AD22 and 809 were able to adhere to Detroit562 and HeLa cells, and invade these epithelial cell lines with a rate comparable to other pathogens as shown by scanning electron microscopy, fluorescence microscopy and replication assays. Infection led to detrimental effects on the cells as deduced from measurements of transepithelial resistance. Mutant strains of putative virulence factors phospholipase D and DIP0733 homologue CULC22_00609 generated in this study showed no influence on colonization under the experimental conditions tested. The data presented here indicate a high infectious potential of this emerging pathogen.

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Section: Introductionmentioning

confidence: 92%

Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources

et al. 2015

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“…Up to now, data on adhesion and invasion of epithelial cells, fibrinogen, fibronectin and collagen binding, antimicrobial profiles and arthritogenic potential of isolates were published. [26][27][28] In the study presented here, C. ulcerans 809 and BR-AD22 were characterized for the first time to our knowledge in respect to their interaction with macrophages as important part of the innate immune system in order to get deeper insight into the pathogenicity of this emerging pathogen. The interaction with macrophages was of special interest, since the closely related animal pathogen Corynebacterium pseudotuberculosis, a facultative intracellular bacterium, is able to survive and grow in macrophages in order to disseminate within the host, 3,29 and also the human pathogen C. diphtheriae is able to survive within human macrophages.…”

Section: Introductionmentioning

confidence: 99%

The killing of macrophages byCorynebacterium ulcerans

et al. 2015

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Corynebacterium ulcerans is an emerging pathogen transmitted by a zoonotic pathway with a very broad host spectrum to humans. Despite rising numbers of infections and potentially fatal outcomes, data on the molecular basis of pathogenicity are scarce. In this study, the interaction of 2 C. ulcerans isolates - one from an asymptomatic dog, one from a fatal case of human infection - with human macrophages was investigated. C. ulcerans strains were able to survive in macrophages for at least 20 hours. Uptake led to delay of phagolysosome maturation and detrimental effects on the macrophages as deduced from cytotoxicity measurements and FACS analyses. The data presented here indicate a high infectious potential of this emerging pathogen.

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“…in patients. A few studies in the mouse model have started to investigate tissue tropism and inflammatory responses (14), revealing strain-dependent arthritogenic potential independent of toxin and phospholipase D production (15,16).…”

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confidence: 99%

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids

et al. 2017

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Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic Corynebacterium strains directly bound to recombinant Mincle in vitro. Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcR␥) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular C. diphtheriae strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors.KEYWORDS C-type lectin receptor, Mincle, Toll-like receptor, macrophage, Corynebacterium diphtheriae, cell wall lipids, mycolate, mycolic acid, corynomycolate D iphtheria caused by toxin-producing Corynebacterium diphtheriae is a severe, life-threatening infection, which has become rare in Europe due to the efficacy and coverage of toxoid immunization but still causes a considerable burden of disease globally. Corynebacterium ulcerans and Corynebacterium pseudotuberculosis can also harbor the tox gene encoding diphtheria toxin (1) and in addition may secrete the exotoxin phospholipase D, a virulence factor involved in caseous lymphadenitis of sheep and goats (2, 3). Rates of infections with nontoxigenic strains of C. diphtheriae, including bloodstream infections and endocarditis, appear to be increasing in Europe (4,5). Of the 90 species that comprise the genus Corynebacterium, many inhabit the human skin or mucosa as commensals (6), with C. striatum, C. tuberculostearicum, C. amycolatum, and C. jeikeium being typical examples of skin inhabitants, whereas C. urealyticum and C. glucuronolyticum are frequently found in the urogenital tract. All

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Strain-dependent arthritogenic potential of the zoonotic pathogen Corynebacterium ulcerans

Cited by 25 publications

References 31 publications

Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources

Colonization of human epithelial cell lines by Corynebacterium ulcerans from human and animal sources

The killing of macrophages byCorynebacterium ulcerans

Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids

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