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Nature Communications Feb 2024The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many...
The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein. So far, its structure as well as the mechanism underlining the synthesis have not been clarified. Here we use cryo-electron microscopy (cryo-EM) and functional approaches to study Cgs from A. tumefaciens. We determine the structure of this complex protein machinery and clarify key aspects of CβG synthesis, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain. Our research opens possibilities for combating pathogens that rely on polysaccharide virulence factors and may lead to synthetic biology approaches for producing complex cyclic sugars.
Topics: Humans; Agrobacterium tumefaciens; Brucella abortus; Cryoelectron Microscopy; beta-Glucans; Glucans; Sugars; Glucosyltransferases
PubMed: 38418509
DOI: 10.1038/s41467-024-45415-8 -
Frontiers in Immunology 2024Guanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3....
INTRODUCTION
Guanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3. It comprises the genes for GBP1-to-3, GBP5 and GBP7. In humans, all GBPs are present in a single cluster on chromosome 1. Brucella abortus is a Gram-negative bacterium known to cause brucellosis, a debilitating disease that affects both humans and animals. Our group demonstrated previously that GBPs present on murine chromosome 3 (GBPchr3) is important to disrupt Brucella-containing vacuole and GBP5 itself is important to Brucella intracellular LPS recognition. In this work, we investigated further the role of GBPs during B. abortus infection.
METHODS AND RESULTS
We observed that all GBPs from murine chromosome 3 are significantly upregulated in response to B. abortus infection in mouse bone marrow-derived macrophages. Of note, GBP5 presents the highest expression level in all time points evaluated. However, only GBPchr3-/- cells presented increased bacterial burden compared to wild-type macrophages. Brucella DNA is an important Pathogen-Associated Molecular Pattern that could be available for inflammasome activation after BCV disruption mediated by GBPs. In this regard, we observed reduced IL-1β production in the absence of GBP2 or GBP5, as well as in GBPchr3-/- murine macrophages. Similar result was showed by THP-1 macrophages with downregulation of GBP2 and GBP5 mediated by siRNA. Furthermore, significant reduction on caspase-1 p20 levels, LDH release and Gasdermin-D conversion into its mature form (p30 N-terminal subunit) was observed only in GBPchr3-/- macrophages. In an perspective, we found that GBPchr3-/- mice had increased B. abortus burden and higher number of granulomas per area of liver tissue, indicating increased disease severity.
DISCUSSION/CONCLUSION
Altogether, these results demonstrate that although GBP5 presents a high expression pattern and is involved in inflammasome activation by bacterial DNA in macrophages, the cooperation of multiple GBPs from murine chromosome 3 is necessary for full control of Brucella abortus infection.
Topics: Animals; Mice; Brucella abortus; Brucellosis; Carrier Proteins; DNA, Bacterial; Inflammasomes; GTP-Binding Proteins
PubMed: 38404575
DOI: 10.3389/fimmu.2024.1341464 -
Heliyon Feb 2024In developing countries like Ethiopia, zoonotic diseases pose a significant health and economic burden, with high exposure of farmers to zoonotic infection given the...
In developing countries like Ethiopia, zoonotic diseases pose a significant health and economic burden, with high exposure of farmers to zoonotic infection given the prevailing traditional husbandry practices. A cross-sectional survey involving 388 farmers in the Ada'a district central Ethiopia was conducted to investigate their knowledge, attitudes, and practices (KAP) regarding the transmission of zoonotic diseases. The respondents' mean age was 41.0 ± 10.0 SD years. The majority of respondents (39.4%) were between the ages of 41 and 50, and 90.0% were married. Farmers claimed that conversations with family, colleagues, and friends were the primary sources of zoonoses information. Farmers stated that the primary sources of information on zoonotic diseases as community. They had a relatively low level (66.8%) of knowledge on zoonotic diseases and half of them (54.9%) did not have good information on zoonoses. Three-quarters (75.2%) of the farmers reported that they neither consume meat and milk nor use offal and hide/skin from sick or dead animals. Similarly, 71.1% of them stated that they do not eat meat from regularly aborting sheep/goats, and never consume raw meat and milk. Most of the respondents correctly answered that raw meat (82.7%) and raw milk (79.9%) are means of disease transmission from animals to humans. However, considerable proportions of them were unaware of zoonotic transmission of bovine tuberculosis (61.3%) and brucellosis (74.7%) transmission through raw milk intakes, and risk of taeniasis (71%) due to raw meat consumption. But, considerable proportions had never dewormed (48.7%), or tested their animals for brucellosis (82.7%) and bovine tuberculosis (83.3%), and more than three quarters (77.3%) did not used personal protective equipment when handling sick animals. Farmers who had a secondary education or above (OR = 6.8, CI = 2.4-18.0, p = 0.004), aged between 41 and 50 years (OR = 3.0, 95% CI: 1.2-7.2, p = 0.015), and those having good knowledge (OR = 2.1, CI = 1.3-3.5, p = 0.002), and positive attitude related to zoonotic diseases (OR = 7.8, CI = 4.7-12.9, p < 0.001) had better practices that reduce the risk of exposure to zoonotic infections than their counterparts. This study revealed a knowledge gaps, a low level of the desired attitude, and high-risk behavioral practices which call for awareness creation about zoonotic disease transmission.
PubMed: 38384538
DOI: 10.1016/j.heliyon.2024.e25713 -
The Canadian Journal of Infectious... 2024Brucellosis is a widespread zoonotic disease of veterinary and public health importance with considerably higher prevalence in developing/underdeveloped countries. This...
Brucellosis is a widespread zoonotic disease of veterinary and public health importance with considerably higher prevalence in developing/underdeveloped countries. This study reports the prevalence and risk determinants of brucellosis in small ruminants of peri-urban and rural areas of district Multan, Southern Punjab, Pakistan. For this purpose, sera samples ( = 392) of small ruminants were collected and subjected to preliminary screening using commercially available RBPT reagents followed by serodetection of brucellosis using multispecies i-ELISA kit (ID.vet, France). All the ELISA positive samples were confirmed by PCR using genus-specific primers, and frequencies of species in positive samples were enumerated using species-specific primers. Results indicated seropositivity rates of 9.69, 9.95, and 10.20% in study population using RBPT reagents of IDEXX-USA, ID.Vet-France, and VRI-Pakistan, respectively, with a statistically nonsignificant difference ( > 0.05). Results of ELISA showed an overall seroprevalence rate of 7.14% in target population with a slightly higher rate in sheep (7.65%) as compared to goat (6.63%) population ( = 0.695; OR = 1.16, 95% CI = 0.53, 2.57). Results revealed that out of total positive samples, was detected in 60.71% of seropositive samples and was detected in 14.28% of positive samples. It was revealed that risk factors including body condition scores, hygienic conditions of the housing facility, farming system, reproductive disorders, educational status of farmers, and awareness of farmers about brucellosis had significant association with brucellosis in small ruminants of study area ( < 0.05). Conversely, farm/herd size, locality, gender, age, weight, and parity showed a nonsignificant association ( > 0.05) with brucellosis. In conclusion, brucellosis is prevalent in small ruminants of Multan, Pakistan. It is recommended to devise and implement effective control strategies with a major focus on raising awareness about brucellosis in farmers for the containment of infection in the region.
PubMed: 38384430
DOI: 10.1155/2024/8898827 -
Frontiers in Veterinary Science 2024is the causative agent of brucellosis in cattle and in humans, resulting in economic losses in the agricultural sector and representing a major threat to public health....
INTRODUCTION
is the causative agent of brucellosis in cattle and in humans, resulting in economic losses in the agricultural sector and representing a major threat to public health. Elk populations in the American Northwest are reservoirs for this bacterium and transmit the agent to domestic cattle herds. One potential strategy to mitigate the transmission of brucellosis by elk is vaccination of elk populations against ; however, elk appear to be immunologically distinct from cattle in their responses to current vaccination strategies. The differences in host response to between cattle and elk could be attributed to differences between the cattle and elk innate and adaptive immune responses. Because species-specific interactions between the host microbiome and the immune system are also known to affect immunity, we sought to investigate interactions between the elk microbiome and infection and vaccination.
METHODS
We analyzed the fecal and vaginal microbial communities of -vaccinated and unvaccinated elk which were challenged with during the periparturient period.
RESULTS
We observed that the elk fecal and vaginal microbiota are similar to those of other ruminants, and these microbial communities were affected both by time of sampling and by vaccination status. Notably, we observed that taxa representing ruminant reproductive tract pathogens tended to increase in abundance in the elk vaginal microbiome following parturition. Furthermore, many of these taxa differed significantly in abundance depending on vaccination status, indicating that vaccination against affects the elk vaginal microbiota with potential implications for animal reproductive health.
DISCUSSION
This study is the first to analyze the vaginal microbiota of any species of the genus and is also the first to assess the effects of vaccination and challenge on the vaginal microbiome.
PubMed: 38352039
DOI: 10.3389/fvets.2024.1334858 -
MSphere Mar 2024Brucellosis, caused by the bacterium , poses a significant global threat to both animal and human health. Although commercial live vaccines including S19, RB51, and...
UNLABELLED
Brucellosis, caused by the bacterium , poses a significant global threat to both animal and human health. Although commercial live vaccines including S19, RB51, and Rev1 are available for animals, their unsuitability for human use and incomplete efficacy in animals necessitate the further study of vaccine-mediated immunity to . In this study, we employed B-cell depletion, as well as immunodeficient and transgenic mouse models, to comprehensively investigate the roles of B cells, antigen uptake and presentation, antibody production, and class switching in the context of S19-mediated immunity against brucellosis. We found that antibody production, and in particular secretory IgM plays a protective role in S19-mediated immunity against virulent early after the challenge in a manner associated with complement activation. While T follicular helper cell deficiency dampened IgG production and vaccine efficacy at later stages of the challenge, this effect appeared to be independent of antibody production and rather was associated with altered T-cell function. By contrast, B-cell MHCII expression negatively impacted vaccine efficacy at later timepoints after the challenge. In addition, B-cell depletion after vaccination, but before the challenge, enhanced S19-mediated protection against brucellosis, suggesting a deleterious role of B cells during the challenge phase. Collectively, our findings indicate antibody production is protective, while B-cell MHCII expression is deleterious, to live vaccine-mediated immunity against brucellosis.
IMPORTANCE
is a neglected zoonotic pathogen with a worldwide distribution. Our study delves into B-cell effector functions in live vaccine-mediated immunity against brucellosis. Notably, we found antibody production, particularly secretory IgM, confers protection against virulent in vaccinated mice, which was associated with complement activation. By contrast, B-cell MHCII expression negatively impacted vaccine efficacy. In addition, B-cell depletion after vaccination, but before the challenge, enhanced protection against infection, suggesting a detrimental B-cell role during the challenge phase. Interestingly, deficiency of T follicular helper cells, which are crucial for aiding germinal center B cells, dampened vaccine efficacy at later stages of challenge independent of antibody production. This study underscores contrasting and phase-dependent roles of B-cell effector functions in vaccine-mediated immunity against .
Topics: Mice; Animals; Humans; Brucella abortus; Brucellosis; Brucella melitensis; Brucella Vaccine; B-Lymphocytes; Vaccines, Attenuated; Mice, Transgenic
PubMed: 38349167
DOI: 10.1128/msphere.00750-23 -
Heliyon Feb 2024In Ethiopia, , Leptospira Hardjo, and spp are recognized as the primary factors contributing to cattle reproductive issues. A cross-sectional study was conducted in...
In Ethiopia, , Leptospira Hardjo, and spp are recognized as the primary factors contributing to cattle reproductive issues. A cross-sectional study was conducted in southwest Ethiopia from October 2020 to October 2021 to assess the risk of reproductive disorders associated with L. Hardjo, , and spp. Moreover, the study aimed to identify the factors associated with reproductive disorders. Using an indirect ELISA, antibodies against these pathogens were observed in serum samples collected from 461 cattle. We employed multivariable random effect logistic regression analysis to identify potential risk factors associated with reproductive disorders in cattle. The study areas showed a prevalence of 25.16 % (95 % CI: 21.20-29.12) for cattle reproductive disorders. The presence of Leptospira Hardjo (OR = 2.9, 95 % CI: 1.17-4.02) and (OR = 3.0, 1.49-5.94) antibodies was associated to the occurrence of cattle reproductive disorders. Seropositivity to pathogens , , and L. Hardjo, along with co-infection of all three, showed association with cattle abortion. The presence of L. Hardjo seropositivity and co-infection with were related to dystocia in cattle. Cattle with retained fetal membranes were associated with co-infection seropositivity to these pathogens. Additionally, seropositivity was linked to cases of repeated breeding in cattle. Age, breeding practices, and dog access to cattle showed associations with reproductive disorders, with odds ratios of 2.3 (95 % CI: 2.03-4.69), 2.9 (95 % CI: 1.83-4.82), and 6.5 (95 % CI: 1.04-2.53) respectively. This research indicates that , , and Leptospira Hardjo, which are responsible for severe zoonotic diseases, have a substantial negative impact on cattle production by causing reproductive disorders. To address the transmission of these diseases, it is essential to implement effective mitigation strategies and enhance public awareness. Additional investigation is necessary to identify and understand the factors contributing to cattle reproductive disorders in the specified area.
PubMed: 38327482
DOI: 10.1016/j.heliyon.2024.e25558 -
Frontiers in Immunology 2023Inflammation plays a key role in the pathogenesis of neurobrucellosis where glial cell interactions are at the root of this pathological condition. In this study, we...
Inflammation plays a key role in the pathogenesis of neurobrucellosis where glial cell interactions are at the root of this pathological condition. In this study, we present evidence indicating that soluble factors secreted by -infected astrocytes activate microglia to induce neuronal death. Culture supernatants (SN) from -infected astrocytes induce the release of pro-inflammatory mediators and the increase of the microglial phagocytic capacity, which are two key features in the execution of live neurons by primary phagocytosis, a recently described mechanism whereby -activated microglia kills neurons by phagocytosing them. IL-6 neutralization completely abrogates neuronal loss. IL-6 is solely involved in increasing the phagocytic capacity of activated microglia as induced by SN from -infected astrocytes and does not participate in their inflammatory activation. Both autocrine microglia-derived and paracrine astrocyte-secreted IL-6 endow microglial cells with up-regulated phagocytic capacity that allows them to phagocytose neurons. Blocking of IL-6 signaling by soluble gp130 abrogates microglial phagocytosis and concomitant neuronal death, indicating that IL-6 activates microglia via trans-signaling. Altogether, these results demonstrate that soluble factors secreted by -infected astrocytes activate microglia to induce, via IL-6 trans-signaling, the death of neurons. IL-6 signaling inhibition may thus be considered a strategy to control inflammation and CNS damage in neurobrucellosis.
Topics: Humans; Microglia; Brucella abortus; Astrocytes; Interleukin-6; Inflammation
PubMed: 38322014
DOI: 10.3389/fimmu.2023.1343503 -
Cureus Jan 2024Brucellosis is an infectious illness contracted by humans through the consumption of unpasteurized milk and dairy items. organisms are diminutive, gram-negative,...
INTRODUCTION
Brucellosis is an infectious illness contracted by humans through the consumption of unpasteurized milk and dairy items. organisms are diminutive, gram-negative, non-motile, and non-spore-forming facultative intracellular, aerobic intracellular coccobacilli residing within the reproductive organs of host animals, leading to conditions such as abortions and sterility. Numerous species of have been identified, with the following four exhibiting varying degrees of pathogenicity in humans: (originating from sheep), (associated with pigs), (linked to cattle), and (found in dogs). and demonstrate the highest level of pathogenicity, while and exhibit a more moderate degree of pathogenicity. The illness can progress to systemic involvement, with the musculoskeletal system being particularly susceptible to complications. Spinal epidural abscess is an infrequent complication that may occur during spondylitis caused by species. Epidural abscesses most commonly affect the lumbar vertebrae, while their involvement in the cervical spine is relatively rare.
OBJECTIVE
In this review, we explore spine brucellosis, covering its epidemiology, pathogenesis, clinical manifestations, diagnostics, and evolving treatments. We aim to enhance early detection, timely intervention, and patient outcomes.
PATIENTS AND METHODS
This retrospective chart analysis was conducted by revising all medical files for patients in whom spinal brucellosis was diagnosed and managed.
RESULTS
This study was conducted at King Hussein Medical Center (KHMC), Jordan, and included a total of 20 patients who were diagnosed with spine brucellosis during the study period. Within the final cohort, 65% of the patients were male (13/20), with an average age at diagnosis of 47.53±14.98 years (ranging from 4 to 61 years). The female group, on the other hand, had an average age at diagnosis of 51.12±15.55 years (ranging from 3 to 58 years). Statistical analysis of the data revealed no significant demographic differences between the two groups. Regarding the co-morbidities, no statistical differences were observed between the two groups. Examining the occupational status of the two groups, no differences were observed. Also, no differences were observed between the two groups regarding the residence place, or the spinal segment involved.
CONCLUSION
Spine brucellosis, although uncommon, poses a complex clinical challenge. Early diagnosis and a multidisciplinary approach are crucial for effective management. Further research is needed to refine diagnostic tools and treatment guidelines for spine brucellosis.
PubMed: 38318596
DOI: 10.7759/cureus.51761 -
Frontiers in Microbiology 2024Human brucellosis causes serious public health concerns in Ningxia, China.
OBJECTIVE
Human brucellosis causes serious public health concerns in Ningxia, China.
METHODS
This study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies.
RESULTS
Between 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including bv. 1, bv. 2, bv. 3, bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, bv. 1 and bv. 3, and . These data highlight the high species/biovars and host diversity of the population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, , emphasizing the requirement for strengthening surveillance of . Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and , indicating that all strains belong to the East Mediterranean lineage. cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia.
CONCLUSION
The epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge.
PubMed: 38314436
DOI: 10.3389/fmicb.2024.1320845