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Emerging Microbes & Infections Dec 2023The zoonotic bacteria, , is becoming the leading cause of canine brucellosis in Europe. In dogs, it causes reproductive problems as well as non-specific lameness or... (Review)
Review
The zoonotic bacteria, , is becoming the leading cause of canine brucellosis in Europe. In dogs, it causes reproductive problems as well as non-specific lameness or discospondilitis. In humans, can be origin of chronic debilitating conditions characteristic to its genus such as undulant fever, splenomegaly, and lymphadenopathy. Although shows some pathogenic characteristics similar to and , it lacks surface O-polysaccharide, like nonzoonotic . This review shows that host- interactions are still poorly understood, with many knowledge and capability gaps, causing relatively poor sensitivity and specificity of existing diagnostic tools. Currently, there is no vaccine for this rough species. Besides, antimicrobial therapy does not guarantee bacterial elimination, and infection relapses are frequently reported, increasing the risks of antibiotic resistance development. has been detected in dogs in almost all European countries which increased human exposure, but currently there is no systematic surveillance. Moreover, caused brucellosis is not included in Animal Health Law, and therefore there is no legal framework to tackle this emerging infectious disease. To map out the diagnostic strategies, identify risks for human infections and propose management scheme for infected pet and kennel dogs, we present current understanding of canine caused brucellosis, outline major knowledge gaps and propose future steps. To address and highlight challenges veterinary and public health services encounter in Europe, we developed two infection scenarios: of a single household pet and of a kennel dog in larger group.
Topics: Animals; Dogs; Humans; Sheep; Brucella canis; Public Health; Dog Diseases; Brucellosis; Europe
PubMed: 37649455
DOI: 10.1080/22221751.2023.2249126 -
Frontiers in Immunology 2023The mechanism of Brucella infection regulating macrophage phenotype has not been completely elucidated until now. This study aimed to determine the mechanism of in the...
OBJECTIVES
The mechanism of Brucella infection regulating macrophage phenotype has not been completely elucidated until now. This study aimed to determine the mechanism of in the modulation of macrophage phenotype using RAW264.7 cells as a model.
MATERIALS AND METHODS
RT-qPCR, ELISA and flow cytometry were used to detect the inflammatory factor production and phenotype conversion associated with M1/M2 polarization of macrophages by infection. Western blot and immunofluorescence were used to analyze the role of nuclear factor kappa B (NF-κB) signaling pathway in regulation of -induced macrophage polarization. Chromatin immunoprecipitation sequencing (Chip-seq), bioinformatics analysis and luciferase reporter assay were used to screen and validate NF-κB target genes associated with macrophage polarization and further verify its function.
RESULTS
The results demonstrate that induces a macrophage phenotypic switch and inflammatory response in a time-dependent manner. , infection-induced M1-type increased first, peaked at 12 h, and then decreased, whereas the M2-type decreased first, trough at 12 h, and then increased. The trend of intracellular survival of was consistent with that of M2 type. When NF-κB was inhibited, M1-type polarization was inhibited and M2-type was promoted, and the intracellular survival of increased significantly. Chip-seq and luciferase reporter assay results showed that NF-κB binds to the glutaminase gene (). expression was down-regulated when NF-κB was inhibited. Furthermore, when was inhibited, M1-type polarization was inhibited and M2-type was promoted, the intracellular survival of increased significantly. Our data further suggest that NF-κB and its key target gene play an important role in controlling macrophage phenotypic transformation.
CONCLUSIONS
Taken together, our study demonstrates that infection can induce dynamic transformation of M1/M2 phenotype in macrophages. Highlighting NF-κB as a central pathway that regulates M1/M2 phenotypic transition. This is the first to elucidate the molecular mechanism of regulation of macrophage phenotype switch and inflammatory response by regulating the key gene , which is regulated by the transcription factor NF-κB.
Topics: NF-kappa B; Brucella abortus; Glutaminase; Signal Transduction; Macrophages
PubMed: 37325614
DOI: 10.3389/fimmu.2023.1180837 -
The EMBO Journal Jul 2023The facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic...
The facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic reticulum. However, little is known about the interplay between the intracellular bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers substantive mitochondrial network fragmentation, accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles during the late steps of cellular infection. Brucella-induced expression of the mitophagy receptor BNIP3L is essential for these events and relies on the iron-dependent stabilisation of the hypoxia-inducible factor 1α. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit from the host cell as BNIP3L depletion drastically reduces the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.
Topics: Brucella abortus; Mitophagy; Vacuoles; Endoplasmic Reticulum; Mitochondria
PubMed: 37232029
DOI: 10.15252/embj.2022112817 -
Veterinary Medicine and Science Jul 2023Most Brucella infections take place on mucosal membranes. Therefore, creating vaccinations delivered through the mucosa may be crucial for managing brucellosis....
BACKGROUND
Most Brucella infections take place on mucosal membranes. Therefore, creating vaccinations delivered through the mucosa may be crucial for managing brucellosis. Consequently, we assessed the efficacy of a recombinant oral antigen delivery system based on Lactococcus lactis for Brucella abortus omp25 antigen.
METHOD
Oral vaccinations with L. lactis transformed with pNZ8148 variants encoding for omp25 (pNZ8148:omp25) and free-pNZ8148 were administered to mice. On day 30, following immunization in animal groups, anti-omp25-specific IgG1 antibodies were assessed by the ELISA test. Additionally, nasal and bronchoalveolar lavages containing omp25-specific secretory IgA (sIgA) were analysed by ELISA. ELISA test and real-time PCR were also used to analyse cytokine responses up to 28 days following the last boost. In addition, the protective potential of L. lactis pNZ8148:omp25 vaccines was assessed in BALB/c mice by exposing them to the B. abortus strain.
RESULTS
Based on the initial screening results, the omp25 protein was identified for immunogenicity because it had the maximum solubility and flexibility and antigenic values of 0.75. The produced plasmid was digested using KpnI and XbaI. By electrophoretic isolation of the digestion fragments at 786 bp, the omp25 gene, the successful production of the recombinant plasmid, was confirmed. Antigen expression at the protein level revealed that the target group generated the 25 kDa-sized omp25 protein, but there was no protein expression in the control group. Fourteen days after priming, there was a considerable amount of omp25-specific IgG1 in the sera of mice vaccinated with pNZ8148-Usp45-omp25-L. lactis (p < 0.001 in target groups compared to the phosphate-buffered saline control group). IFN-γ and TNF-α levels were more significant in samples from mice that had been given the pNZ8148-Usp45-omp25-L. lactis and IRBA vaccinations, in samples taken on days 14 and 28, respectively (p < 0.001). The pNZ8148-Usp45-omp25-L. lactis and IRBA immunization groups had significantly greater IL-4 and IL-10 transcription levels than the other groups. The spleen portions from the pNZ8148-Usp45-omp25-L. lactis and IRIBA vac group had less extensive spleen injuries, alveolar oedema, lymphocyte infiltration and morphological damage due to the inflammatory process.
CONCLUSION
Our study offers a novel method for using the food-grade, non-pathogenic and noncommercial bacterium L. lactis as a protein cell factory to produce the novel immunogenic fusion candidate romp25. This method offers an appealing new approach to assessing the cost-effective, safe, sustainable, simple pilot development of pharmaceutical products.
Topics: Animals; Mice; Antigens, Bacterial; Bacterial Vaccines; Brucella abortus; Brucella Vaccine; Brucellosis; Immunoglobulin G; Lactococcus lactis; Mice, Inbred BALB C
PubMed: 37276346
DOI: 10.1002/vms3.1173 -
Pathogens (Basel, Switzerland) Sep 2023is an intracellular parasitic bacterium that uses multiple strategies to evade the host's defense mechanisms. However, how manipulates the host-induced oxidative...
is an intracellular parasitic bacterium that uses multiple strategies to evade the host's defense mechanisms. However, how manipulates the host-induced oxidative stress and relevant biological processes are still poorly understood. In this study, a comparative transcriptome assay of macrophages infected with S2308 and its rough mutant RB14 was performed to investigate the differentially expressed genes which might be associated with the pathogenic mechanism of . Our results showed that numerous host pro-oxidative and antioxidative stress genes were differentially expressed in macrophages infected with S2308 and mutant RB14 at 4, 8, 24, and 48 h post-infection. Interestingly, we found that several ferroptosis-associated genes were differentially expressed during RB14 infection. Moreover, we found that the rough mutant RB14-induced macrophage death was associated with reduced levels of host glutathione and glutathione peroxidase 4, together with increased free iron, lipid peroxidation, and ROS, all of which are important hallmarks of ferroptosis. The ferroptosis occurring during infection with RB14 was reduced by treatment with the inhibitor ferrostatin-1. However, S2308 infection did not induce these hallmarks of ferroptosis. Taken together, our results demonstrate that ferroptosis is involved in rough infection. Investigating how manipulates oxidative stress and ferroptosis in its host will be helpful to clarify the pathogenicity of .
PubMed: 37887705
DOI: 10.3390/pathogens12101189 -
Frontiers in Veterinary Science 2023
PubMed: 37520004
DOI: 10.3389/fvets.2023.1245623 -
Veterinary Medicine International 2023Despite the implementation of brucellosis eradication programs in Iran, this disease is still endemic and highly prevalent among ruminants in this country. The infection...
Despite the implementation of brucellosis eradication programs in Iran, this disease is still endemic and highly prevalent among ruminants in this country. The infection of small ruminants with may play a significant role in the continuation of brucellosis among the herds of ruminants. This study investigated the proportion of and in 150 samples of sheep and goat's raw milk which were obtained from Lorestan and Hamadan provinces in the western part of Iran using the PCR method. The results revealed that among the spp. positive samples, 26.5% and 73.4% of the samples were infected with and , respectively. The incidence rates of among the sheep and goats samples were 6.8% and 12.5%, respectively. There was a significant difference between goats and sheep regarding the proportion of . Three samples (2%) (2 goats and one sheep) were simultaneously infected with both and . This article renews our knowledge about the causative agent of brucellosis in small ruminants and shows that has a relatively high prevalence among those animals in the western regions of Iran, and its role as one of the main factors of abortion among small ruminants should not be ignored. The information provided in the present study is important for the surveillance program, as eradication programs and strategies to prevent the spread of among small ruminants that have not been vaccinated against this microorganism may be adapted accordingly.
PubMed: 38044961
DOI: 10.1155/2023/6751152 -
Infection Ecology & Epidemiology 2023Brucellosis is a worldwide zoonosis that is endemic in Namibia. This study estimated seroprevalence of brucellosis, and determined the presence of infection in...
Brucellosis is a worldwide zoonosis that is endemic in Namibia. This study estimated seroprevalence of brucellosis, and determined the presence of infection in slaughtered cattle using the genus-specific 16-23S rRNA interspacer PCR (ITS-PCR), and the species-specific AMOS-PCR. Between December 2018 and May 2019, sera ( 304), pooled lymph nodes ( 304), and individual spleen ( 304) were collected from slaughtered cattle from 52 farms. Sera were tested for anti-Brucella antibodies using the Rose Bengal test (RBT), and the complement fixation test (CFT). Seroprevalence was 2.3% (7/304) (RBT) and 1.6% (5/304) (CFT). Prevalence of positive herds was 9.6% (5/52). Lymph node ( 200) and spleen ( 200) samples from seronegative cattle tested negative for spp. DNA on ITS-PCR, but spp. DNA was detected in lymph nodes (85.7%, 6/7) and spleen (85.7%, 6/7) from RBT positive cattle. ITS-PCR confirmed isolates from lymph node (51.4%, 4/7) and spleen (85.7%, 6/7) as spp.; while AMOS-PCR and species specific (BaSS) PCR confirmed the isolates as , and field strains, respectively. Provision of adequate protective gear, and the promotion of brucellosis awareness among abattoir workers is recommended to prevent zoonotic infection.
PubMed: 37398877
DOI: 10.1080/20008686.2023.2229589 -
Infection and Drug Resistance 2023Brucellosis is a serious public health issue in Qinghai (QH), China. Surveying the seroprevalence and isolation of strains from marmots is key to understanding the role...
OBJECTIVE
Brucellosis is a serious public health issue in Qinghai (QH), China. Surveying the seroprevalence and isolation of strains from marmots is key to understanding the role of wildlife in the maintenance and spread of brucellosis.
METHODS
In this study, a set of methods, including a serology survey, bacteriology, antibiotic susceptibility, molecular genotyping (MLST and MLVA), and genome sequencing, were employed to characterize the two strains.
RESULTS
The seroprevalence of brucellosis in marmots was 7.0% (80/1146) by serum tube agglutination test (SAT); one strain was recovered from these positive samples, and another strain from a human. Two strains were identified as bv. 1 and were susceptible to all eight drugs examined. The distribution patterns of the accessory genes, virulence associated genes, and resistance genes of the two strains were consistent, and there was excellent collinearity between the two strains on chromosome I, but they had significant SVs in chromosome II, including inversions and translocations. MLST genotyping identified two strains as ST2, and MLVA-16 analysis showed that the two strains clustered with strains from northern China. WGS-SNP phylogenetic analysis showed that the strains were genetically homogeneous with strains from the northern region, implying that strains from a common lineage were spread continuously in different regions and hosts.
CONCLUSION
Seroprevalence and molecular clues demonstrated frequent direct or indirect contact between sheep/goats, cattle, and marmots, implying that wildlife plays a vital role in the maintenance and spread of in the Qinghai-Tibet Plateau.
PubMed: 38144222
DOI: 10.2147/IDR.S436950