It has been demonstrated that Borrelia hermsii, a causative agent of relapsing fever, produces a factor H (FH) and FH-like protein 1 (FHL-1) binding protein. The binding protein has been designated FhbA. To determine if FH/FHL-1 binding is widespread among B. hermsii isolates, a diverse panel of strains was tested for the FH/FHL-1 binding phenotype and FhbA production. Most isolates (23/24) produced FhbA and bound FH/ FHL-1. Potential variation in FhbA among isolates was analyzed by DNA sequence analyses. Two genetically distinct FhbA types, designated fhbA1 and fhbA2, were delineated, and type-specific PCR primers were generated to allow for rapid differentiation. Pulsed-field gel electrophoresis and hybridization analyses demonstrated that all isolates that possess the gene carry it on a 200-kb linear plasmid (lp200), whereas isolates that lack the gene lack lp200 and instead carry an lp170. To determine if FhbA is antigenic during infection and to assess the specificity of the response, recombinant FhbA1 (rFhbA1) and rFhbA2 were screened with serum from infected mice and humans. FhbA was found to be expressed and antigenic and to elicit a potentially type-specific FhbA response. To localize the epitopes of FhbA1 and FhbA2, truncations were generated and screened with infection serum. The epitopes were determined to be conformationally defined. Collectively, these analyses indicate that FH/FHL-1 binding is a widespread virulence mechanism for B. hermsii and provide insight into the genetic and antigenic structure of FhbA. The data also have potential implications for understanding the epidemiology of relapsing fever in North America and can be applied to the future development of species-specific diagnostic tools.Tick-and louse-borne relapsing fever are significant health concerns in regions of endemicity (4). The impact of relapsing fever on human health can be staggering. In some districts of Tanzania and Ethiopia, approximately 40% of children under the age of 1 develop tick-borne relapsing fever (TBRF), with this infection being one of the top 10 killers of children under the age of 5 (7, 38). In North America, three closely related Borrelia species associated with TBRF exist (Borrelia hermsii, Borrelia turicatae, and Borrelia parkeri) (4). Several outbreaks of TBRF with serious illness have been reported in the United States (5, 14, 36, 40, 41). However, the true incidence of infection is not known because a definitive diagnosis is typically not obtained and the disease is not frequently reported. In addition, it remains to be determined if there is a correlation between severity of disease and the species of the infecting isolate. The lack of well-characterized species-specific antigens has slowed the development of diagnostic assays, epidemiological tools, and vaccines that could be used to diagnose, track, and prevent relapsing fever.We have identified a factor H (FH) and FH-like protein 1 (FHL-1) binding protein expressed by B. hermsii designated FhbA (17,25). The ability to bind FH and FHL-1 has impo...
ObjectiveFive to ten percent of interstitial cystitis/bladder pain syndrome (IC/BPS) patients have Hunner's lesions (HL), areas of non-specific inflammation and scarring. The poor quality of life of patients with HL is entwined in associated pain and loss of bladder capacity. Although the decrease in bladder capacity is usually dependent on pain, it may also be dependent upon scarring and associated compliance changes produced by the inflammatory process. This report reviews the potential role of endoscopic scar lysis using the holmium laser in the management of these patients whose only other therapeutic option is urinary diversion.MethodsTwo patients with HL and “end stage” bladders who underwent holmium laser division of bladder wall scar/tethering were identified. Clinical data were reviewed with emphasis on safety and efficacy.ResultsBoth patients selected for this procedure underwent holmium laser lysis of known scar tissue in an effort to increase bladder capacity and improve symptoms of urinary frequency and pain with bladder filling. The median age of patients who underwent the procedure was 63 (59–67) years. Incisions were made with the holmium laser at frequencies of 3–10 Hz of 300–700 J along the region of scarring. All procedures were performed by the same practitioner. There was an increase in bladder capacity by 58.3% (50.0%–66.7%). During a mean follow-up of 4.2 years, there appeared to be a significant improvement with an increase in interval time between voids and a decrease in pain with bladder filling.ConclusionPatients with IC/BPS may be severely debilitated by a clinically significant decrease in their bladder capacity, especially in the face of HL. The use of the holmium laser to incise regions of scar and bladder wall tethering may produce a clinically significant and durable increase in bladder capacity. The use of this technique as a means of treating bladder scarring poses an excellent adjunct to existing treatment strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.