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Papers by Olena Rakhimova

Scientific Reports, Apr 18, 2017

Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common... more Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2−/− mice that do not have functional B or T cells, and in MyD88−/−, TLR2−/− and TLR4−/− mice that are defective in toll like receptor signaling. The presence of other bacteria had no effect on BabA expression as shown by infection of germ free mice. Moreover, loss of BabA expression was not dependent on Le b expression or the capacity of BabA to bind Le b. Surprisingly, gender was the host determinant most associated with loss of BabA expression, which was maintained to a greater extent in male mice and was associated with greater bacterial load. These results suggest the possibility that loss of BabA expression is not driven by adaptive immunity or toll-like receptor signaling, and that BabA may have other, unrecognized functions in addition to serving as an adhesin that binds Le b. Helicobacter pylori infects the gastric mucosa of about 50% of the world's population 1. The majority of those infected have only asymptomatic gastritis, but about 10% develop peptic ulcer and 1-3% develop gastric cancer 1-3 , which is the third most common cause of cancer death worldwide (~1 million cases per year). Given the large number of infected individuals, increasing development of antibiotic resistance 4,5 , and accumulating evidence that in some people H. pylori may be beneficial 6-9 , treatment of all infected individuals may not be warranted. Therefore, it is important to determine the elements of the host-H. pylori interaction that influence whether an individual will develop clinical disease or asymptomatic infection. One risk factor associated with more severe disease outcomes is the virulence factor, blood group antigen binding adhesin (BabA), which belongs to a family of H. pylori outer membrane proteins 10 that also includes LabA 11 , SabA 12 , and the recently characterized HopQ 13,14. BabA is a well-characterized adhesin 15-18 that binds to ABO blood group antigens, fucosylated carbohydrates expressed on the gastric epithelium and the protective mucus layer. BabA exhibits highest affinity for Lewis b (Le b) 19 , owing to a polymorphic, three-pronged carbohydrate binding domain identified recently by X-ray structural analysis 20,21. Epidemiologic studies of an association of BabA with disease 22,23 are supported by in vitro evidence that BabA-mediated attachment to host gastric epithelium facilitates translocation of the CagA oncoprotein into host cells 24. Translocation occurs via the type IV secretion system encoded on the cytotoxin associated gene pathogenicity island (cagPAI), itself a well-recognized risk factor for disease 25-29. BabA mediated attachment and development of disease are influenced by host expression of Lewis antigens, which is determined by a number of factors, including ABO blood type and secretor status 30-33. The risk of ulcer is increased in individuals with blood group O, and in non-secretor individuals who do not express Le b and ABO antigens on gastric epithelial cells or on mucins 30-34. Thus, disease outcome is related to both bacterial expression of the BabA adhesin and to ABO glycosylation on gastric epithelial cells and gastric mucins.

International Endodontic Journal, 2022

Frontiers in Cellular and Infection Microbiology, 2020

The use of stem cells from the apical papilla (SCAPs) has been proposed as a means of promoting r... more The use of stem cells from the apical papilla (SCAPs) has been proposed as a means of promoting root maturation in permanent immature teeth, and plays a significant role in regenerative dental procedures. However, the role of SCAPs may be compromised by microenvironmental factors, such as hypoxic conditions and the presence of bacteria from infected dental root canals. We aim to investigate oral bacterial modulation of SCAP in terms of binding capacity using flow cytometry and imaging, real-time cell proliferation monitoring, and cytokine secretion (IL-6, IL-8, and TGF-β isoforms) under anaerobic conditions. SCAPs were exposed to key species in dental root canal infection, namely Actinomyces gerensceriae, Slackia exigua, Fusobacterium nucleatum, and Enterococcus faecalis, as well as two probiotic strains, Lactobacillus gasseri strain B6 and Lactobacillus reuteri (DSM 17938). We found that A. gerensceriae, S. exigua, F. nucleatum, and E. faecalis, but not the Lactobacillus probiotic ...

Journal of Clinical Medicine, 2020

Traumatic dental injuries in young individuals are often exposed to the invasion of oral microorg... more Traumatic dental injuries in young individuals are often exposed to the invasion of oral microorganisms that leads to pulp necrosis. Infective necrosis in permanent teeth not-fully-developed causes aberrant root formation. Regeneration endodontic treatments (RETs) have shown promising results by promoting continued root development by stem cells. Critical to the success of RET is the thorough disinfection of the pulpal space. To establish effective antimicrobial protocols for root canal disinfection, the invading microorganisms need to be identified. In the present study, we use a combination of culture-based and high-throughput molecular sequencing techniques to investigate the microbial profiles from traumatized teeth (30 cases) and controls, i.e., teeth with pulp infections not caused by trauma (32 cases). Overall, a high microbial diversity in traumatized necrotic teeth was observed. Eubacterium yurii subsps. yurii and margaretiae, as well as key ‘bridging oral species’ F. nucle...

Thrombosis and haemostasis, May 21, 2016

Wound healing is a complicated biological process that consist of partially overlapping inflammat... more Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen-deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chroni...