The Terminal Immunoglobulin-Like Repeats of LigA and LigB of Leptospira Enhance Their Binding to Gelatin Binding Domain of Fibronectin and Host Cells

Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KD = 1.91±0.40 µM). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction

Exposure and risk factors to Coxiella burnetii, spotted fever group and typhus group rickettsiae, and Bartonella henselae among volunteer blood donors in Namibia

Background: The role of pathogen-mediated febrile illness in sub-Saharan Africa is receiving more attention, especially in Southern Africa where four countries (including Namibia) are actively working to eliminate malaria. With a high concentration of livestock and high rates of companion animal ownership, the influence of zoonotic bacterial diseases as causes of febrile illness in Namibia remains unknown.Methodology/Principal Findings: The aim of the study was to evaluate exposure to Coxiella burnetii, spotted fever and typhus group rickettsiae, and Bartonella henselae using IFA and ELISA (IgG) in serum collected from 319 volunteer blood donors identified by the Blood Transfusion Service of Namibia (NAMBTS). Serum samples were linked to a basic questionnaire to identify possible risk factors. The majority of the participants (64.8%) had extensive exposure to rural areas or farms. Results indicated a C. burnetii prevalence of 26.1% (screening titre 1:16), and prevalence rates of 11.9% and 14.9% (screening titre 1:100) for spotted fever group and typhus group rickettsiae, respectively. There was a significant spatial association between C. burnetii exposure and place of residence in southern Namibia (P0.012), especially cattle (P>0.006), were also significantly associated with C. burnetii exposure. Males were significantly more likely than females to have been exposed to spotted fever (P<0.013) and typhus (P<0.011) group rickettsiae. Three (2.9%) samples were positive for B. henselae possibly indicating low levels of exposure to a pathogen never reported in Namibia.Conclusions/Significance: These results indicate that Namibians are exposed to pathogenic fever-causing bacteria, most of which have flea or tick vectors/reservoirs. The epidemiology of febrile illnesses in Namibia needs further evaluation in order to develop comprehensive local diagnostic and treatment algorithms.Peer reviewedEntomology and Plant Patholog