Brucella melitensis omp31 Mutant Is Attenuated and Confers Protection Against Virulent Brucella melitensis Challenge in BALB/c Mice

Verdiguel-Fernández, L; Oropeza-Navarro, Ricardo; Ortiz, Adolfo; Robles-Pesina, M G; Ramírez-Lezama, José; Castañeda-Ramírez, A; Verdugo-Rodríguez, Antonio

doi:10.4014/jmb.1908.08056

Cited by 11 publications

(5 citation statements)

References 35 publications

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“…At present, some experiments have shown that Omp10, Omp19, Omp25, and Omp31 are involved in Brucella virulence (11)(12)(13). The Brucella Omp19, Omp25, and Omp31 mutant were attenuated in cellular models and in mice, indicating that Omp19 and Omp25 were important for bacterial survival in vitro and in vivo (11,(14)(15)(16)(17). Furthermore, Omp25 and Omp31 disrupt the immune response by regulating the secretion of tumor necrosis factor alpha (TNF-α) expression and apoptosis in porcine and murine macrophages infected models (18,19).…”

Section: Introductionmentioning

confidence: 99%

RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells

et al. 2021

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Brucellosis is an endemic zoonotic infectious disease in the majority of developing countries, which causes huge economic losses. As immunogenic and protective antigens at the surface of Brucella spp., outer membrane proteins (Omps) are particularly attractive for developing vaccine and could have more relevant role in host–pathogen interactions. Omp16, a homolog to peptidoglycan-associated lipoproteins (Pals), is essential for Brucella survival in vitro. At present, the functions of Omp16 have been poorly studied. Here, the gene expression profile of RAW264.7 cells infected with Brucella suis vaccine strain 2 (B. suis S2) and ΔOmp16 was analyzed by RNA-seq to investigate the cellular response immediately after Brucella entry. The RNA-sequence analysis revealed that a total of 303 genes were significantly regulated by B. suis S2 24 h post-infection. Of these, 273 differentially expressed genes (DEGs) were upregulated, and 30 DEGs were downregulated. These DEGs were mainly involved in innate immune signaling pathways, including pattern recognition receptors (PRRs), proinflammatory cytokines, and chemokines by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In ΔOmp16-infected cells, the expression of 52 total cells genes was significantly upregulated and that of 9 total cells genes were downregulated compared to B. suis S2-infected RAW264.7 cells. The KEGG pathway analysis showed that several upregulated genes were proinflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-11, IL-12β, C–C motif chemokine (CCL2), and CCL22. All together, we clearly demonstrate that ΔOmp16 can alter macrophage immune-related pathways to increase proinflammatory cytokines and chemokines, which provide insights into illuminating the Brucella pathogenic strategies.

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Section: Introductionmentioning

confidence: 99%

RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells

et al. 2021

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“…Therefore, seeking for new PLOS NEGLECTED TROPICAL DISEASES candidate antigen to replace LPS is of great significance for developing brucellosis detecting kits which can be easily produced and available to all users. According to literatures, many Brucella OMPs manifested strong capacity in arousing humoral immune response [14][15][16], and some of these proteins have also been used for development of subunit vaccine against brucellosis [17,18]. In our previous study, some Brucella OMPs showed quite satisfactory result in diagnosing brucellosis, basically comparable to LPS antigen [7].…”

Section: Discussionmentioning

confidence: 90%

Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein

Yin

Bai

et al. 2021

PLoS Negl Trop Dis

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Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations.

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“…PG and lipoteichoic acids in human monocytes also have been stated to induce the secretion of this cytokine [ 50 ]. Although the monovalent lysate of E. faecalis did not show a stimulatory effect on either of the two cell types used, the result confirms that bacterial structures vary between genera and species [ 52 , 53 ], which supports the relevance of using immunogens with epitopes expressed by the different microorganisms [ 24 , 30 , 32 ]. In addition, with regard to LPS, it has been reported that in conjunction with bacterial flagellin, it induces TNF-α production [ 54 ].…”

Section: Discussionmentioning

confidence: 74%

“…It is important to note that outer membrane proteins are considered important epitopes for the development of diagnostic systems and mainly vaccines, because of their ability to stimulate the immune response [ 29 , 31 , 32 , 33 ]. The protein composition of the UNAM-HIMFG lysate is very diverse ( Figure 1 A,B); to know if some of these proteins were immunogenic, their reactivity was evaluated by WB assays.…”

Section: Discussionmentioning

confidence: 99%

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections

Acevedo-Monroy,

Rocha-Ramírez,

Martínez Gómez

et al. 2024

IJMS

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Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

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Brucella melitensis omp31 Mutant Is Attenuated and Confers Protection Against Virulent Brucella melitensis Challenge in BALB/c Mice

Cited by 11 publications

References 35 publications

RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells

RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells

Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections

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