Microbial Pathogenesis

Mesenchymal stem cells (MSCs) are multipotent cells commonly derived from the bone marrow, adipose tissue and placenta. Human bone marrow derived MSCs migrate to a site of injury, release proinflammatory cytokines and modulate T-cell proliferation. At sites of injury, MSCs may well encounter bacterial pathogens most commonly the Gram positive pathogen Staphylococcus aureus. However, the precise molecular mechanism(s) of this interaction remain to be elucidated. In the present study we aim to show if a direct interaction occurs between S. aureus and bone marrow derived MSCs and identify if MSCRAMMs have a role in this interaction. We further aim to compare S. aureus interaction with cells that differentiate from MSCs, namely; osteoblasts, adipocytes and chondrocytes, since MSCs co-exist in the niche of these cells. Our results showed that S. aureus is able to interact with MSCs in the form of adhesion and invasion to the cells, and that this interaction is largely dependent on the expression of fibronecting-binding protein (FnBP) by S. aureus. We also showed that the same mechanism of interaction to osteoblasts, adipocytes and chondrocytes that are directly differentiated from the same MSCs. Finally, we have found that the presence of 10% FBS in the infection medium is essential as it helps in achieving the best specific bacterial-cell association with the least background association. The results reveals a mechanism of interaction between S. aureus and MSCs that could pave the way for therapeutic intervention that minimises the burden of infection in inflammatory diseases.

Adipokines have not been studied in acute dengue, despite their emerging role in inducing and regulating inflammation. Therefore, we sought to identify adipokine levels in patients with varying severities of acute dengue to understand their role in disease pathogenesis. We determined the levels of leptin, resistin, omentin, adiponectin, as well as IFN{beta}, and NS1 using quantitative ELISA in patients with dengue fever (DF=49) and dengue haemorrhagic fever (DHF=22) at admission (febrile phase) and at the time of discharge (recovery phase). The viral loads and serotypes of all samples were quantified using quantitative real-time RT-PCR. Resistin levels (p =0.04) and omentin (p=0.006) levels were significantly higher in patients who developed DHF. Omentin levels in the febrile phase also correlated with the AST (Spearmans r=0.38, p=0.001) and ALT levels (Spearmans r=0.24, p=0.04); as well as serum leptin levels with both AST (Spearmans r=0.27, p=0.02) and ALT (Spearmans r=0.28, p=0.02). Serum adiponectin levels in the febrile phase did not correlate with any of the other adipokines or with liver enzymes, but inversely correlated with CRP levels (Spearmans r=-0.31, p=0.008). Although not significant (p=0.14) serum IFN{beta} levels were lower in the febrile phase in those who progressed to develop DHF (median 0, IQR 0 to 39.4 pg/ml), compared to those who had DF (median 37.1, IQR 0 to 65.6 pg.ml). The data suggest that adipokines are likely to play a role in the pathogenesis of dengue, which should be further explored for the potential to be used as prognostic markers and as therapeutic targets.

Metacaspases are cysteine proteases and are found in every group of organisms except animals. They are structural orthologs of caspases, which orchestrate apoptosis in animals. Caspases, metacaspases, paracaspases and orthocaspases are class C14 proteases with a similar active site (the hemoglobinase fold) and a catalytic cysteine residue. However, metacaspases cleave after arginine and lysine instead of aspartate and some researchers point out that a name ending with caspase is unsuitable. Also, most metacaspases are activated by calcium, they do not target the same proteins as caspases and they cut multiply instead of once. The Candida albicans metacaspase Mca1p mediates cell death in response to various stresses but also has pro-life functions. Many plant and protist metacaspases lack cell death roles and are involved in development, differentiation and immunity. This article highlights an interesting phenomenon, whereby the promotion of stress sensitivity and reduction of virulence, by Mca1p in C. albicans cells from exponential culture are abolished and reversed, respectively in cells from stationary-phase culture. This hints at the proteases's dual nature and at the conditions that might initiate a switch between pro-life and pro-death functions.

Background Group B Streptococcus (GBS) is a leading cause of bacterial sepsis globally. Late-onset (LO) GBS disease is preceded by colonization within the gastrointestinal tract in vulnerable neonates. Previous studies demonstrate that Candida albicans (C. albicans) promotes GBS colonization of host tissues including the bladder and vagina. However, its impact on GBS colonization of the intestinal tract is unknown. Methods We established a new animal model to study GBS and C. albicans co-colonization model in the context of the newborn host to examine C. albicans impact on GBS and further evaluated fluconazole prophylactic treatment to these same outcomes. Physical interactions between organisms in vivo were imaged and GBS gene expression was evaluated. Results C. albicans increased GBS burden in the neonatal gut and GBS was physically colocalized with C. albicans hyphae as evidenced by the colocalization analysis. Fluconazole treatment of co-colonized mice decreased extraintestinal GBS dissemination. C. albicans presence upregulated genes encoding proteins responsible for GBS adhesion and invasion of intestinal epithelial cells. Conclusion C. albicans enhances GBS burden and pathogenicity in the neonatal gut. These findings highlight the need for further investigation into C. albicans as a potential risk factor for GBS colonization and LO disease in human infants.

The game theory describes the interactions between two players and the pay-off from wining, losing or compromising. Mycobacterium tuberculosis (Mtb)-host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and three Mtb virulence factors were assessed in broncho-alveolar lavage of TB+ and TB- patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the "Nash equilibrium", Ag85B is the main virulence factor for Mtb in active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation, Mtb can express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-{beta} and IDO. Consistently, The IDO expression was 134-times higher in TB+s than the TB-s, and the T-bet expression, ~200-times higher in the TB-s than the TB+s. Furthermore, Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO.

BackgroundHLA-B27 is a class I MHC protein that is associated with different diseases collectively called, spondyloarthropathies. It includes; 2. Ankylosing spondylitis, which causes inflammation of the bones in your spine 3. Reactive arthritis, which causes inflammation of your joints, urethra, and eyes, and in some cases lesions on your skin 4. Juvenile rheumatoid arthritis 5. Anterior Uveitis, which causes swelling and irritation in the middle layer of your eye ObjectivesTo determine the prevalence of HLA-B27 in patients with backache at the Armed Forces Institute of Pathology in Rawalpindi. This descriptive cross-sectional study was conducted between June 2020 and Nov 2020. Material and methodsOf the 243 patients, 167 males and 76 females were tested for HLA-B27 during the study period. Venous blood samples (3 mL) were collected in EDTA tubes and processed for HLA-B27 gene identification on the cell surface. A two-color flow cytometry panel was used to analyze samples using a BD FACS Canto II flow cytometer on BD FACS Diva software. The dot plot was created using an isotype control in four quadrants, and positive and negative populations of cells were identified. ResultsA total of 243 patients were analyzed for the presence of HLA-B27 using flow cytometry. Of the 243 patients, 167 were male and 76 were female patient.51 male patients tested positive, with a positivity rate of 30.53% among the male population and 20.98% among the general population. In contrast to the male population, 12 female patients tested positive for the HLA-B27 gene, with a positivity rate of 15.78% among the female population and 4.93% among the general population. The total positivity rate was 25.92%, with a higher prevalence in the male population included in this study. ConclusionAll individuals tested for HLA B27 were included in this study. This study showed that positivity rate of HLA-B27 is more in males with a percentage of 20.98% as compared to female population (4.93%).

Klebsiella quasivariicola was a novel strain of Klebsiella species and had potential pathogenicity. Our previously studies showed dopamine, one of the most commonly used rescue drugs for critically ill patients, had clear effects on the growth of K. quasivariicola in culture medium, however, its effects on host immune system were ignored. Therefore, in consideration of the host immunity, the interactions of K. quasivariicola, dopamine and macrophages were explored. In this study, RAW264.7 cells and C57/BL6 mice were infected with K. quasivariicola, and the bacterial growth in macrophage, the production of inflammatory cytokines and the pathological changes of mice lung were detected, in the absence or presence of dopamine. Our results showed dopamine inhibited the K. quasivariicola growth in medium, but promoted the bacterial growth when K. quasivariicola was co-cultured with macrophages; The expression of proinflammatory cytokines in K. quasivariicola infected RAW 264.7 were increased, while a sharp rise was observed with the addition of dopamine; Infection of K. quasivariicola to mice induced an inflammatory response and lung injury, which were exacerbated by dopamine administration. It can be concluded that dopamine administration resulted in a significantly increase of K. quasivariicola burdens in the presence of macrophage, consequently, aggravated the inflammatory response and inflammatory injury. ImportanceDopamine is one of the most commonly used rescue drugs for critically ill patients. Here we indicated K. quasivariicola was a potential pathogen of pulmonary infection, and dopamine significantly increased the proliferation of K. quasivariicola when exposed to macrophage, subsequently result in severe inflammatory response and inflammatory injury. We also proposed an in vitro model of microbes-drugs-host immune cells that could better mimic in vivo environment and more suitable for the studies of inhibitor screening. This fundamental work had contributed to the present understanding of the crosstalk between pathogen, dopamine and host immune cells. Furthermore, our data showed dopamine was one of the risk factors for patients with K. quasivariicola infection, which provided a basis for clinical precision medicine.

In 2021, 273 Rocky Mountain Spotted Fever cases have been reported nationwide. In Chihuahua City, fourteen samples were obtained from children suspected of rickettsial infection. The analysis of samples collected from January to December 2021 showed a prevalence of 28.5%, 43% and 28.5% for Rickettsia rickettsii, Ehrlichia canis, and both pathogens in coinfection, respectively. The analysis of clinical hematological and biochemistry analytes showed alterations such as 100% of the children coursed with elevated liver enzymes and coagulation times, 64% showed leukocytosis due to neutrophilia, 55% of them had thrombocytopenia, lymphopenia and hypoalbuminemia, and 45% showed normocytic normochromic anemia. Statistically significant differences were obtained in the chemokines IL-8, RANTES, CXCL9/MIG, and CXCL10/IP-10 across the coinfected and control groups; the differences in IP-10 were significant for patients infected by R. rickettsii compared to the control group. Also, significant differences were observed for IL-1{beta}, IL-6, IL-17, IFN{gamma}, and TNF among the R. rickettsii positive group compared to the control group; on the other hand; the coinfected group exhibited modified levels of IL-6, IL-8, and IL-10 compared with the control group. Finally, significant differences were obtained for CD8 + T lymphocytes subpopulations between positive individuals for R. rickettsii and E. canis.

To investigate how host cells respond to the hijacking of host cells by Listeria monocytogenes (LM) and affect their gene expression in the process of infection by LM. In this study, three data lines in the GEO database were used for differential expression analysis. The results showed that 34 co-expressed genes (DEGs) were selected from the differential expression analysis of three data lines. Among them, 30 genes were co-up-regulated and 4 genes were co-down-regulated. In the blood test group, 131 genes were up-regulated and 28 genes were down-regulated. In the liver, 132 genes were up-regulated and 18 genes were down-regulated. In the spleen, 142 genes were up-regulated and 11 genes were down-regulated. Among the 30 upregulated IDEGs, GBP3, MB21D1, FPR2, SAMHD1, CXCL10, STAT2, IRF1, and STAT1 genes were involved in the defense response to the virus, type i interferon signaling pathway, and inflammatory response. Functional enrichment analysis revealed that 30 up-regulated genes were enriched in cytoplasmic spermatoproteasome complex, proteasome core complex, and cell membrane lateral signaling pathway, which were involved in the regulation of threonine-type endopeptidase activity and guanosine triphosphate (GTP) signaling process.

BackgroundIntestinal parasitic infections (IPIs) are a public health issue affecting young children in low and middle income countries (LMICs). These factors may induce malnutrition, as well as systemic and/or intestinal inflammation, depending on the species, intensity of infection, and host response. This study aimed at determining the effect of intestinal parasites on nutritional status and inflammatory responses in pre- and school-aged children in rural areas of the southern province of Rwanda. MethodsA cross-sectional study involving 127 children under 12 years of age was conducted at two health centers in Huye District, Southern Province, Rwanda, from January to February 2022. A structured questionnaire was used to collect sociodemographic information, feeding habits, anthropometric measurements, and information on infection/malnutrition risk factors. Stool samples were collected to test for intestinal parasites by using microscope, while serum was collected to measure (anti)inflammatory markers [interleukin-10 (IL-10), tumour necrosis factor-alpha (TNF-), total protein, and C-reactive protein (CRP)]. ResultsThe overall prevalence of IPIs was 38.6%, with non-pathogenic Entamoeba coli being the most prevalent (21.3%), followed by Ascaris lumbricoides (18.1%), Entamoeba histolytica (11.8%), and Trichuris trichiura (1.6%). Coinfections accounted for 12.6% of the infections. Moreover, 48.0%, 25.2%, and 9.4% of the children were stunted, underweight, and stunted, respectively. Underweight, IL-10, and total protein levels were significantly associated with IPIs. Our findings also indicated that food supplements had a significant positive effect on stunting. ConclusionAscaris lumbricoides, Entamoeba histolytica, and Trichuris trichiura were the predominant parasites. Intestinal parasitic infections in preschool children and schoolchildren affect the nutritional status, possibly through chronic inflammation. Further mechanistic investigations will shed more light on the regulation of the inflammatory response.

Aeromonas hydrophila is a primary bacterial pathogen affecting freshwater fish, including Labeo rohita (rohu), leading to significant losses in aquaculture. This study investigates the probable role of intimin/invasin, known virulence factors in several bacterial pathogens, in the pathogenesis of A. hydrophila in L. rohita. Using an in-silico approach, we explore the genetic and structural features of these proteins to predict their potential function in facilitating infection. We analysed the distribution of invasin and intimin across 53 A. hydrophila genomes and examined their physicochemical properties, including molecular weight and stability. Additionally, we evaluated the secondary structures to understand their functional roles in host-pathogen interactions. Using homology-based modelling, we generated 3D (tertiary) structures of invasin and intimin and selected the most suitable models for in silico docking experiments with all eight Rohu (Labeo rohita) {beta}-integrins-a crucial step in understanding their interactions with the fish (Rohu) host cells. Due to the unavailability of the crystal structure of Rohu {beta}-integrins, we performed homology-based modelling prior to the docking experiments. Our findings reveal that invasin and intimin are present in only 6 of the 53 A. hydrophila strains examined, primarily in highly virulent strains previously reported. Notably, invasin lacks disulfide bonds and beta turns. 3D modelling indicates a significant binding affinity of invasin with all human {beta}-integrins, suggesting a critical role in host-pathogen interactions.

Little is currently known about the regulation of PL fimbriae produced by some pathogenic E. coli strains. We identified PlfB, a transcriptional regulator of the PapB family, as a negative regulator of PL fimbriae (Plf). Deletion of plfB significantly increased plfA transcription and Plf production. PlfB bound specifically to the plfA promoter region. Using a PplfA-lux reporter system, the deletion of plfB caused sustained and increased expression across serial passages. Global regulatory genes such as lrp, argR, and hns were also implicated in regulation of plf expression. Loss of lrp or argR decreased plf expression, suggesting these regulators positively regulate PL fimbriae. By contrast, loss of hns increased levels of plf expression, supporting its role as a negative regulator. Interestingly, loss of plfB significantly increased bacterial colonization in the lung of 6-day-old turkey poults. Further, complementation of plfB restored plf fimbrial expression and colonization of turkey lungs to wild-type levels. This further supports an important role for PL fimbriae for colonization of turkey lungs, since loss of plfB which resulted in increased plf gene expression in turkey lungs also correlated with higher bacterial numbers in the lungs. Taken together, these results indicate that PlfB acts as a negative regulator to reduce levels of PL fimbrial expression, under some conditions, but that it is not required for plf expression. This contrasts with the role the PapB regulator, which has been shown to play an essential role in expression of P fimbriae in uropathogenic E. coli strains.

Brucella abortus is a pathogen that survives in macrophages. Several virulence factors participate in this process, including the open reading frame (ORF) BAB1_0270 codifying of a Zinc-dependent metalloproteinase. Here, its contribution in the process of intracellular adaptation was analyzed by infecting RAW264.7 macrophages with the mutant B. abortus {Delta}270 strain. Results showed that this Zinc-dependent metalloproteinase is a cytoplasmic protein that conforms an operon with a transcriptional regulator, which may constitute a type II toxin-antitoxin system. Functionally, this Zinc-dependent metalloproteinase participated neither in the adherence nor the initial intracellular traffic of B. abortus in macrophages. Nevertheless, its deletion significantly increased the co-localization of B. abortus {Delta}270 with phagolysosomal cathepsin D, reducing both its co-localization with calnexin, present in endoplasmic reticulum derived vesicles, and its intracellular replication within macrophages. Besides, B. abortus {Delta}270-infected macrophages produced significantly higher levels of TNF-, IL-6, CD80 and CD86 than B. abortus 2308, even when several genes involved in virulence (vjbR, hutC, bvrR, virB1) were up-regulated in this mutant. Finally, its deletion significantly reduced the capacity of B. abortus {Delta}270 to adapt, grow and express several virulence factors under acidic conditions. Based on these results, we discuss the role of this Zinc-dependent metalloproteinase in the regulation of the virulence of this pathogen, concluding that it contributes significantly to the intracellular adaptation of B. abortus 2308 during the infection of macrophages. Author summaryBrucella abortus is the causative agent of the brucellosis, a highly contagious diseases. A Zinc-dependent metalloproteinase contributes significantly in the intracellular survival. Here, we demonstrate that this metalloproteinase has homology with ImmA/IrrE proteases, which are involved in the bacterial resistance to hostile environment. Furthermore, it conforms a gene pair with a transcriptional regulator, being required by B. abortus to escape from phagolysosomes, to achieve the endoplasmic reticulum and replicate within macrophages. Its deletion from B. abortus stimulated the macrophages, which produced higher levels of pro-inflammatory cytokines and co-stimulatory proteins. This pathogen showed a reduced ability to adapt and grow under acidic conditions, which would negatively affect its escape from phagolysosomes and consequently, stimulating macrophages. Therefore, this work describes how this Zinc-dependent metalloproteinase significantly contributes in the intracellular adaptation of B. abortus 2308 in macrophages.

Cell-mediated immunity (CMI), which includes T-cells (both T helper and cytotoxic), is critical for effective antiviral defenses against coronavirus disease-2019 (COVID-19). To better understand the immunological characteristics of CD markers on T-cells in post-COVID-19 patients, we investigated the expression of differential CD markers in the patient groups in this study. Flow cytometry was used to quantify total lymphocyte count and assess the levels of expression of CD markers in the samples. The percentage of Lymphocytes decreased significantly in the post-SARS-COV-2 patients in comparison to normal subjects, which is usually happening in any viral infection. In contrast to that, expression of CD8 was increased in the patient group having long SARS-COV-2 infection with comorbid complications with respect to the normal individuals and long SARS-COV-2 infection without comorbid complications. This data revealed that the cellular immunological responses corroborated with an earlier report of COVID-19 infection were mediated by CD8 upregulation and cytotoxic T lymphocyte hyperactivation.

Infections with Pasteurella multocida can cause significant zoonotic respiratory problems in both humans and animals. In vivo tests in mouse infection models were used to investigate the mechanisms of respiratory epithelial barrier dysfunction during respiratory bacterial infection with these pathogens. Results revealed that P. multocida infection significantly increased epithelial permeability and increased expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in murine tracheae and lungs. In murine lung epithelial cell (MLE-12) models, P. multocida infection decreased the expression of tight junctions (ZO-1) and adherens junctions ({beta}-catenin, E-cadherin), but induced the activation of the hypoxia-inducible factor-1 (HIF-1) and VEGFA signaling. When expression of HIF-1 is suppressed, the induction of VEGFA and ZO-1expression by P. multocida infection is decreased. We also found that intervention of HIF-1 and VEGFA signaling affected infection outcomes caused by respiratory bacteria in mouse models. Most importantly, we demonstrated that P. multocida infection increased permeability of human respiratory epithelial cells and this process was associated with the activation of the HIF-1 and VEGFA signaling and likely contributes to the pathogenesis of P. multocida in humans. ImportanceMammalian respiratory epithelium forms the first line of defense against infections with Pasteurella multocida, an important zoonotic respiratory pathogen. In this study, we found P. multocida infection increased respiratory epithelial permeability and promoted the induction of the hypoxia-HIF-1-VEGFA axis in both mouse and murine cell models. Similar findings were also demonstrated in human respiratory epithelial cells. The results from this study gain important knowledge about the pathogenesis of P. multocida causing infections in both animals and humans.

Dengue virus (DENV) infection causes an acute febrile illness that is usually self-limiting but can become fatal. Thrombocytopenia, or a decrease in circulating platelets, is a major clinical feature of dengue and is strongly associated with the progression to dengue hemorrhagic fever and dengue shock syndrome. In this report, MYH9, a cytoskeletal protein involved in platelets maturation and release, was found to be down-regulated in DENV-infected Huh7 cell lines. The expression of RUNX1, an important transcription factor involved in megakaryopoiesis, was also decreased following DENV-infection. In-silico analysis identified three potential RUNX1 transcription-factor binding site in the promoter-region of MYH9 gene. We therefore investigated whether RUNX1 regulates MYH9 expression during DENV-infection. Luciferase-assay and ChIP assays showed that DENV-infection affect the binding of RUNX1 to the MYH9 promoter, providing insight into the molecular basis underlying the reduced expression of MYH9 expression. Furthermore, the megakaryocyte differentiation markers GATA1, ITGB3, and MYH9 were upregulated in PMA-induced K562-cells. However, DENV infection downregulated these genes and increased the expression of apoptosis marker gene CYCS. These findings suggest that the dengue affects megakaryopoiesis through multiple mechanisms, potentially reducing platelets production while also promoting platelets destruction. Additionally, Fluorescence and electron microscopy revealed that functional defects of MYH9 may affects megakaryopoiesis biogenesis. Overall, this study provides insights into the molecular mechanisms contributing to thrombocytopenia during DENV infection.

Microsporidia are difficult to completely eliminate. Their persistence may disrupt host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia infection upon dendritic cells (DCs). We used the zoonotic microsporidia species, Enterocytozoon hellem, in our studies. In vivo experiments showed that E. hellem-infected mice were more susceptible to further pathogenic challenges. DCs were identified as the most affected group of cells. In vitro assays revealed that E. hellem infection impaired the immune functions of DCs as reflected by down-regulation of cytokine expression, lower extent of maturation and antigen presentation. E. hellem infection decreased the ability of DCs to prime and stimulate T cells, thereby hampering host immune cell functions. We further demonstrate that E. hellem Ser/Thr protein phosphatase PP1 directly interacts with host p38(MAPK14) to manipulate the p38 (MAPK14)/NFAT-5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs immune functions. The emerging of microsporidiosis may be great threat to public health. HighlightsO_LIPersistence of Microsporidia within host impairs dendritic cell functions such as phagocytosis, maturation, antigen presentation and T cell priming, thereby disrupting both innate and adaptive immunities and making the host more vulnerable to secondary infections C_LIO_LIMicrosporidia impairs DCs function via Serine/Threonine Protein Phosphatase PP1 directly targeting DCs p38/MAPK pathway C_LIO_LILatent Microsporidia infection and persistence is a great threat to public health when assessing acute and emerging pathogen risk C_LI

The eukaryotic protozoan Entamoeba gingivalis (E.g.) is strongly associated with inflamed periodontal pockets. Unlike other obligate anaerobic Entamoeba species, it is considered to not have a life cycle of actively dividing trophozoites and dormant cysts. Accordingly, it has been regarded as non-infectious. To investigate if E.g is capable of encystation in response to adverse environmental conditions, we cultivated clinical isolates of E.g. collected from inflamed periodontal pockets in antibiotics for 8 days. The cytomorphological and ultrastructure forms of the amoeba were investigated by transmission and scanning electron microscopy to reveal cyst formation. We observed exocysts and the encapsulated trophozoids separated by an intra-cystic space, a dense poorly vesiculated cytoplasma and polygonal surface areas of cysts. The cysts walls were composed of chitin. Cysts were conspicuously smaller compared to trophozoids and lacked pseudo- and filipodia. We did not observe multi-nucleated trophozoids after antibiotic induces encystation. Cyst formation in E.g may explain why established treatment approaches often do not stop periodontal tissue destruction during periodontitis and periimplantitis.

Bacillus cereus biovar anthracis (Bcbva) strains, which cause fatal anthrax-like disease, have been isolated from animals in Central and West Africa. Like B. anthracis, Bcbva produces a poly-{gamma}-D-glutamic acid (PDGA) capsule, as well as edema factor (EF), lethal factor (LF) and protective antigen (PA). Bcbva also possesses a hyaluronic acid capsule that is not expressed by B. anthracis. The pathogenesis of Bcbva has recently been characterized in inhalational infection models, in rabbits and guinea pigs. Here, we characterized the ki-netics of Bcbva infection and toxin production in a murine model of cutaneous infection using the Bcbva CA strain isolated in Cameroon. We found that spore germination oc-curred rapidly at the inoculation site, followed by bacterial dissemination to the draining cervical lymph nodes. Germination was associated with rapid production and diffusion of LF and EF. Bacteria rapidly disseminated to lymphoid organs and other compartments, with distal germination observed 18 hours post-infection. Infected mice developed septi-cemia within 24 hours, accompanied by high circulating LF levels and signs of cardiac and renal injury. These findings may contribute to the fulminant course of Bcbva infection observed in animals and highlight its potential risk to humans.

Pseudorabies virus (PRV) is an immunosuppressive disease that causes significant damage to the pig industry. This study aimed to detect the effects of PRV on oxidative stress related factors and cell apoptosis in the spleen, providing a basis for the research on the pathogenesis of PRV in mice model. Pathological observation was performed by hematoxylin and eosin Y staining. Biochemical and Flow cytometry method were performed to determine the reactive oxygen species profile of the spleen post-infection and apoptosis detection. In addition, q-PCR and Western blot were adopted to measure the apoptotic conditions of the spleen infected with PRV. The results indicated that the ROS level in the PRV infection group was remarkedly increased (p<0 01) at a time-dependent pattern. Furthermore, the Malondialdehyde levels in the spleen of mice in the infection group increased significantly (p<0.01) in a time-dependent mode. However, the Catalase, Superoxide dismutase, and Glutathione activity and expression levels in the infection group were significantly decreased with the control group (p<0 01) in a time-dependent manner. Furthermore, the ratio of splenocyte apoptosis in the infection group significantly increased (p<0 05, p<0 01) in a time-dependent manner. In conclusion, PRV infection causes apoptosis of the spleen via oxidative stress in mice.