The Mechanism of Facultative Intracellular Parasitism of Brucella

Hu, Jiao; Zhou, Zhixiong; Li, Bowen; Xiao, Yinlong; Li, Mengjuan; Zeng, Han; Guo, Xi; Gu, Guojing

doi:10.3390/ijms22073673

Cited by 61 publications

(50 citation statements)

References 84 publications

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“…are small (0.5-0.7 by 0.6-1.5 µm), non-motile, non-spore-forming, slowgrowing, facultative intracellular Gram-negative coccobacilli belonging to the Brucellaceae family along with the Mycoplana and Ochrobactrum spp. [1,2]. Brucellae can infect several animal species and currently comprise 12 well-classified species, 4 of which causing almost the totality of human infections: B. melitensis, B. abortus, B. suis, and B. canis, with B. melitensis being the most virulent [3].…”

Section: Laboratory Diagnosis Of Brucella Infectionmentioning

confidence: 99%

Microbiological Laboratory Diagnosis of Human Brucellosis: An Overview

et al. 2021

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Brucella spp. are Gram-negative, non-motile, non-spore-forming, slow-growing, facultative intracellular bacteria causing brucellosis. Brucellosis is an endemic of specific geographic areas and, although underreported, represents the most common zoonotic infection, with an annual global incidence of 500,000 cases among humans. Humans represent an occasional host where the infection is mainly caused by B. melitensis, which is the most virulent; B. abortus; B. suis; and B. canis. A microbiological analysis is crucial to identifying human cases because clinical symptoms of human brucellosis are variable and aspecific. The laboratory diagnosis is based on three different microbiological approaches: (i) direct diagnosis by culture, (ii) indirect diagnosis by serological tests, and (iii) direct rapid diagnosis by molecular PCR-based methods. Despite the established experience with serological tests and highly sensitive nucleic acid amplification tests (NAATs), a culture is still considered the “gold standard” in the laboratory diagnosis of brucellosis due to its clinical and epidemiological relevance. Moreover, the automated BC systems now available have increased the sensitivity of BCs and shortened the time to detection of Brucella species. The main limitations of serological tests are the lack of common interpretative criteria, the suboptimal specificity due to interspecies cross-reactivity, and the low sensitivity during the early stage of disease. Despite that, serological tests remain the main diagnostic tool, especially in endemic areas because they are inexpensive, user friendly, and have high negative predictive value. Promising serological tests based on new synthetic antigens have been recently developed together with novel point-of-care tests without the need for dedicated equipment and expertise. NAATs are rapid tests that can help diagnose brucellosis in a few hours with high sensitivity and specificity. Nevertheless, the interpretation of NAAT-positive results requires attention because it may not necessarily indicate an active infection but rather a low bacterial inoculum, DNA from dead bacteria, or a patient that has recovered. Refined NAATs should be developed, and their performances should be compared with those of commercial and home-made molecular tests before being commercialized for the diagnosis of brucellosis. Here, we review and report the most common and updated microbiological diagnostic methods currently available for the laboratory diagnosis of brucellosis.

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Section: Laboratory Diagnosis Of Brucella Infectionmentioning

confidence: 99%

Microbiological Laboratory Diagnosis of Human Brucellosis: An Overview

et al. 2021

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“…Additionally, further analysis with markers of different endosomal, Golgi-and ER-derived compartments are necessary to further characterize the trafficking of the Brucellacontaining vacuole along the endosomal pathway and its ERmediated remodeling (Piersanti et al, 2015). For further reading on the survival cycle in host cells by the facultative intracellular bacteria, Brucella, please refer to the recent review by Jiao, et al (Jiao et al, 2021).…”

Section: Trafficking Of Brucella-containing Vacuole Along the Endosomal Pathwaymentioning

confidence: 99%

“…For further reading on the survival cycle in host cells by the facultative intracellular bacteria, Brucella , please refer to the recent review by Jiao, et al. ( Jiao et al., 2021 ).…”

Section: Trafficking Of Brucella -Containing Vacuole Along the Endosomal Pathwaymentioning

confidence: 99%

Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

Vaughn

Kwaik

2021

Front. Cell. Infect. Microbiol.

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While most bacterial species taken up by macrophages are degraded through processing of the bacteria-containing vacuole through the endosomal-lysosomal degradation pathway, intravacuolar pathogens have evolved to evade degradation through the endosomal-lysosomal pathway. All intra-vacuolar pathogens possess specialized secretion systems (T3SS-T7SS) that inject effector proteins into the host cell cytosol to modulate myriad of host cell processes and remodel their vacuoles into proliferative niches. Although intravacuolar pathogens utilize similar secretion systems to interfere with their vacuole biogenesis, each pathogen has evolved a unique toolbox of protein effectors injected into the host cell to interact with, and modulate, distinct host cell targets. Thus, intravacuolar pathogens have evolved clear idiosyncrasies in their interference with their vacuole biogenesis to generate a unique intravacuolar niche suitable for their own proliferation. While there has been a quantum leap in our knowledge of modulation of phagosome biogenesis by intravacuolar pathogens, the detailed biochemical and cellular processes affected remain to be deciphered. Here we discuss how the intravacuolar bacterial pathogens Salmonella, Chlamydia, Mycobacteria, Legionella, Brucella, Coxiella, and Anaplasma utilize their unique set of effectors injected into the host cell to interfere with endocytic, exocytic, and ER-to-Golgi vesicle traffic. However, Coxiella is the main exception for a bacterial pathogen that proliferates within the hydrolytic lysosomal compartment, but its T4SS is essential for adaptation and proliferation within the lysosomal-like vacuole.

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“…The Th1 immune response is essential for the clearance of Brucella infection, and the antimicrobial effects of pro-inflammatory cytokines, including IFN-γ and TNF-α, have been established [ 6 ]. However, Brucella can subvert the protective immune response and consequently establish a chronic infection [ 7 ]. Previous mouse model studies have shown that Brucella may modify virulence factors, such as lipopolysaccharide (LPS), proline racemase protein A (PrPA), and toll-like receptor/IL-1R (TIR)-containing protein, which in turn affect the levels of IFN-γ, TNF-α, IL-10, and TGF-β1.…”

Section: Introductionmentioning

confidence: 99%

Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

Sun

Tang

et al. 2021

BMC Infect Dis

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Background The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. Methods Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People’s Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-β1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. Results The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-β1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-β1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). Conclusions Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-β1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

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The Mechanism of Facultative Intracellular Parasitism of Brucella

Cited by 61 publications

References 84 publications

Microbiological Laboratory Diagnosis of Human Brucellosis: An Overview

Microbiological Laboratory Diagnosis of Human Brucellosis: An Overview

Idiosyncratic Biogenesis of Intracellular Pathogens-Containing Vacuoles

Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

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