Pathological changes, distribution and detection of<i>Brucella melitensis</i>in foetuses of experimentally-infected does

Mazlan, Mazlina; Khairani-Bejo, Siti; Hamzah, Hazilawati; Nasruddin, Nurrul Shaqinah; Salleh, Annas; Zamri‐Saad, Mohd

doi:10.1080/01652176.2020.1867328

Cited by 7 publications

(11 citation statements)

References 30 publications

(26 reference statements)

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“…Here, immunoreaction to Brucella yielded positive results in scattered cells in the umbilical cord, as well as in the areas of inflammation and in Kupffer cells in the liver. Positive immunoreactivity has been reported similarly in the umbilical cord and liver of stillborn and neonatal dogs infected with B. canis, 11 in the liver of a bovine fetus infected with B. abortus, 38 and in ovine, caprine, and mouse fetuses infected with B. melitensis, 24,28,46 mainly in macrophages located in periportal areas and in Kupffer cells.…”

Section: Discussionmentioning

confidence: 57%

“…Brucella detection utilizing IHC in cattle, ovine, caprine, bison, canine, and dolphin fetuses similarly revealed a cytoplasmic reaction in alveolar macrophages and occasionally in neutrophils, and was extracellular in the luminal debris and meconium. 4,11,28,38,41 B. abortus and B. melitensis infection in bison and caprine fetuses, respectively, cause splenic necrosis. 28,41 We observed less severe lesions in porcine fetuses, characterized by a lack of development of white pulp components.…”

Section: Discussionmentioning

confidence: 99%

“…4,11,28,38,41 B. abortus and B. melitensis infection in bison and caprine fetuses, respectively, cause splenic necrosis. 28,41 We observed less severe lesions in porcine fetuses, characterized by a lack of development of white pulp components. This contrasts with the white pulp hyperplasia reported in the B. melitensis infection of goat fetuses 28 and bovine abortions caused by B. abortus or B. abortus RB51, 13,32,48 and could be explained by the greater pathogenicity of these Brucella species, especially B. melitensis.…”

Section: Discussionmentioning

confidence: 99%

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Histopathologic and immunohistochemical findings in the placentas and fetuses of domestic swine naturally infected with Brucella suis biovar 2

et al. 2023

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Porcine brucellosis, which is caused by Brucella suis biovar (bv) 2, is a re-emerging disease that causes reproductive problems in pigs in Europe. The pathogenesis and lesions of B. suis intrauterine infection are poorly characterized; characterization could facilitate the diagnosis and investigation of porcine brucellosis. We collected samples of placentas and fetuses for histologic and microbiologic studies during an outbreak of abortions on a pig-breeding farm in Spain. Brucella was cultured from the vaginal swabs obtained from sows that had aborted, some placentas, and fetal tissues (spleen, liver, lung, gastric content); molecular testing confirmed B. suis bv 2 infection. Histologically, there was necrotizing and hemorrhagic placentitis; suppurative hepatitis; lymphoid depletion and sinusoidal histiocytosis in the spleen, lymph nodes, and thymus; and bronchointerstitial pneumonia. Hemorrhages were observed in the umbilical cord, heart, kidneys, and brain. We detected Brucella by immunohistochemistry (IHC) in all of the placentas and fetal organs studied, specifically in the trophoblasts of the chorionic epithelium, in the cytoplasm of macrophages in the chorionic stroma, and extracellularly in necrotic debris. Furthermore, we assessed the lymphocyte population in the placentas through the use of IHC (anti-CD3, anti- Pax5 antibodies), revealing that the lymphocytic response was composed of T cells but not B cells.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Histopathologic and immunohistochemical findings in the placentas and fetuses of domestic swine naturally infected with Brucella suis biovar 2

et al. 2023

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“…In this study, comparative genomics and reverse vaccinology methods were used for identification of protective vaccine antigens against Brucella melitensis , which is a Gram-negative coccobacillus bacterium from the Brucellaceae family [ 16 ]. B. melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis

et al. 2023

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The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs. Infected animals also represent the major source of infection for humans. Development of safer and effective vaccines for brucellosis remains a priority to support disease control and eradication in animals and to prevent infection to humans. In this research study, we designed an in-silico multi-epitopes vaccine for B. melitensis using computational approaches. The pathogen core proteome was screened for good vaccine candidates using subtractive proteomics, reverse vaccinology and immunoinformatic tools. In total, 10 proteins: catalase; siderophore ABC transporter substrate-binding protein; pyridoxamine 5’-phosphate oxidase; superoxide dismutase; peptidylprolyl isomerase; superoxide dismutase family protein; septation protein A; hypothetical protein; binding-protein-dependent transport systems inner membrane component; and 4-hydroxy-2-oxoheptanedioate aldolase were selected for epitopes prediction. To induce cellular and antibody base immune responses, the vaccine must comprise both B and T-cells epitopes. The epitopes were next screened for antigenicity, allergic nature and water solubility and the probable antigenic, non-allergic, water-soluble and non-toxic nine epitopes were shortlisted for multi-epitopes vaccine construction. The designed vaccine construct comprises 274 amino acid long sequences having a molecular weight of 28.14 kDa and instability index of 27.62. The vaccine construct was further assessed for binding efficacy with immune cell receptors. Docking results revealed that the designed vaccine had good binding potency with selected immune cell receptors. Furthermore, vaccine-MHC-I, vaccine-MHC-II and vaccine-TLR-4 complexes were opted based on a least-binding energy score of −5.48 kcal/mol, 0.64 kcal/mol and −2.69 kcal/mol. Those selected were then energy refined and subjected to simulation studies to understand dynamic movements of the docked complexes. The docking results were further validated through MMPBSA and MMGBSA analyses. The MMPBSA calculated −235.18 kcal/mol, −206.79 kcal/mol, and −215.73 kcal/mol net binding free energy, while MMGBSA estimated −259.48 kcal/mol, −206.79 kcal/mol and −215.73 kcal/mol for TLR-4, MHC-I and MHC-II complexes, respectively. These findings were validated by water-swap and entropy calculations. Overall, the designed vaccine construct can evoke proper immune responses and the construct could be helpful for experimental researchers in formulation of a protective vaccine against the targeted pathogen for both animal and human use.

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“…En la literatura aparecen descritos diversos ensayos que realizan el cultivo de muestras animales con varias especies de Brucella en medios selectivos. En particular, se ha reportado la siembra de muestras de pequeños rumiantes inoculados con cepas virulentas de B. melitensis, Rev1 o mutantes atenuados derivados en FM Kahl-McDonagh et al, 2006;Mazlan et al, 2021;, en FM modificado -según y en Thayer-Martin modificado -según . El hecho de que estos medios presenten sensibilidad variable en función de la cepa a aislar y, además, que todos ellos incluyan concentraciones elevadas de polimixinas debe ser considerado a la hora de comparar resultados independientes.…”

Section: Discusión General Y Conclusiones Discusión General Y Trabajo...unclassified

Estudio del sistema Wzm/Wzt en Brucella y evaluación del candidato vacunal Rev1∆wzm frente a la brucelosis ovina

Mena-Bueno¹

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Brucellosis is a zoonotic disease caused by bacteria of the genus Brucella, that also entails large economic losses. The main infection source for humans are ruminants, in which the disease induces abortion and other reproductive disorders. In most affected regions, vaccinating animals is the only realistic strategy to control the infection. The attenuated strain B. melitensis Rev1 is the only recommended vaccine against ovine and caprine brucellosis, but it has several drawbacks, such as virulence when administered in pregnant animals, serological interference, possibility of infecting humans, and resistance to treatments including streptomycin, that urge the search for new vaccines. The smooth lipopolysaccharide (S-LPS) is a well-known virulence factor and the immunodominant antigen in diagnostic tests, thus, its modifications represent an interesting approach in the research for a safe vaccine. Among S-LPS biosynthesis pathways, the Wzm/Wzt two-component system is the responsible of transporting the O-PS synthesised onto the cytoplasmic side of the inner membrane to the periplasm, for its subsequent assembly to the core-lipid A to form the S-LPS. Blocking this pathway leads to the generation of rough LPS (R-LPS) mutants capable of accumulating O-PS within the bacteria, that may be decisive for an effective immune response against the infection. However, the biological implications of each transporter protein are still unknown. In particular, the O-PS blockage could lead to modifications in bacterial envelope, since the O-PS transport requires the participation of bactoprenol as a carrier molecule, that is also involved in the biosynthesis of other cellular structures. Aiming to deepen the knowledge about this system and its potential application in vaccines development, in Chapter 1 of this thesis, it is presented the construction and characterisation of single and double Δwzm/Δwzt mutants derived from Rev1. In addition, for comparative purposes, ∆wzm mutants were constructed from B. abortus 2308 and S19 and studied together with a 16M∆wzm mutant, derived from the B. melitensis 16M virulent strain previously developed in the Animal Health Group of the Institute of Agrobiotechnology (IdAB). As a result, the mutants lacking outer O-PS exhibited changes in gene expression, antigenic properties of inner O-PS, and phenotypic changes associated with outer membrane and/or cell wall modifications. In addition, Rev1 ∆wzm/∆wzt mutants were highly susceptible to polymyxins and other antibiotics used in human brucellosis treatment, particularly, to streptomycin; and they showed a large attenuation in mouse. Among them, Rev1∆wzm stood out for inducing a transient peak of splenomegaly, being highly immunogenic, and generating effective protection against B. melitensis and B. ovis virulent infections in murine model. In Chapter 2, prior to studying the safety of Rev1∆wzm in the natural host, it was determined the ability of this vaccine candidate to grow in Farrell (FM) and CITA (CM) selective culture media, currently recommended for Brucella primary isolation. The mutant strong susceptibility to polymyxins and the synergy between colistin and vancomycin observed led to the severe inhibition of the vaccine candidate in both selective media. To solve this, the named Brucella Selective Medium (BSM) was reformulated and evaluated with more than 1,700 ovine field samples, being able to improve the previous media performance. Furthermore, by exploring the productivity of BSM for other brucellae, it was observed that both BSM and CM inhibited the growth of a B. abortus bv1 strains collection. The analysis of the possible causes led to the development of a second selective medium called Brucella Selective Improved Culture (BruSIC), which was permissive for all the Brucella strains analysed, and as inhibitory as CM for the usual contaminant bacteria in veterinary samples. In addition, BruSIC offers the advantage of not requiring bovine serum to isolate serum-dependent Brucella strains, simplifying medium preparation, lowering costs and avoiding the use of compounds from animal sources. In Chapter 3, it was analysed the safety and immune response induced in lambs inoculated with Rev1∆wzm, demonstrating the activation of antibodies development without interfering in the standard serological tests for brucellosis diagnosis. These results, as well as others achieved by the research group in adult cattle and pregnant sheep, make this mutant a promising vaccine candidate to control B. melitensis and B. ovis infections in small ruminants. The content of these three thesis chapters has been published in the scientific journals Frontiers in Microbiology (Frontiers group) and Microbiology Spectrum (ASM).

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Pathological changes, distribution and detection ofBrucella melitensisin foetuses of experimentally-infected does

Cited by 7 publications

References 30 publications

Histopathologic and immunohistochemical findings in the placentas and fetuses of domestic swine naturally infected with Brucella suis biovar 2

Histopathologic and immunohistochemical findings in the placentas and fetuses of domestic swine naturally infected with Brucella suis biovar 2

Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis

Estudio del sistema Wzm/Wzt en Brucella y evaluación del candidato vacunal Rev1∆wzm frente a la brucelosis ovina

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