The<i>Brucella abortus</i>Phosphoglycerate Kinase Mutant Is Highly Attenuated and Induces Protection Superior to That of Vaccine Strain 19 in Immunocompromised and Immunocompetent Mice

Trant, Cyntia G. M. C.; Lacerda, Thaís Lourdes Santos; Carvalho, Natália B.; Azevedo, Vasco; Rosinha, G. M. S.; Salcedo, Suzana P.; Gorvel, Jean‐Pierre; Oliveira, Sérgio C.

doi:10.1128/iai.01433-09

Cited by 37 publications

(29 citation statements)

References 39 publications

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“…Our research group has previously demonstrated the virulence of the vaccine strains S19 and RB51 in IRF-1 KO mice. Only 70 to 80% of IRF-1 KO mice inoculated with S19 at 10 6 CFU survived the first 4 weeks after infection, while all mice inoculated with RB51 at 10 6 or 10 8 CFU survived the first 4 weeks (21,26). Our data suggest the following order of virulence in IRF-1 KO mice: the S2308 strain Ͼ ⌬omp19:: kan strain Ͼ ⌬mfp::kan strain.…”

Section: Resultsmentioning

confidence: 68%

“…Previous studies from our laboratory have identified genes related to survival and virulence in B. abortus (13,14,21,26). Here, we investigated the importance of the Brucella proteins Mfp and Omp19 in microbial pathogenesis by evaluating the persistence of the B. abortus gene replacement ⌬omp19::kan and ⌬mfp::kan mutant strains both intracellularly and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Three days after seeding, another 0.1 ml of LCCM was added. On the 7th day, the medium was renewed, and on the 10th day, the cells were completely differentiated into macrophages (21).…”

Section: Methodsmentioning

confidence: 99%

“…The strain B. abortus S2308(pBBR4-gfp) generated by conjugation was obtained from our laboratory stock. The complementation experiments were performed using the entire mfp or omp19 gene inserted into the plasmid pBBR1MCS (with chloramphenicol resistance) that replicates in Brucella, resulting in the complemented ⌬mfp(pBBR1-mfp) or ⌬omp19(pBBR1-omp19) strain as previously described by our group (21). GFP was also expressed in complemented mutant strains by conjugation using the plasmid pBBR4-gfp as described above.…”

Section: Methodsmentioning

confidence: 99%

“…The B. abortus ⌬mfp::kan and ⌬omp19::kan defined deletion mutants were constructed by gene replacement as described previously (21). The mfp or omp19 wild-type gene was replaced by double homologous recombination with the mfp or omp19 allele containing the kanamycin resistance gene, resulting in the ⌬mfp::kan or ⌬omp19::kan mutant strain (Table 1).…”

Section: Methodsmentioning

confidence: 99%

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Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice

et al. 2015

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f Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus ⌬mfp::kan and ⌬omp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a ⌬mfp::kan or ⌬omp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus ⌬omp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the ⌬mfp::kan strain had a lower virulence in these same mouse models. Furthermore, ⌬mfp::kan and ⌬omp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the ⌬mfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a ⌬omp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the ⌬mfp::kan mutant may serve as a potential vaccine candidate in future studies. Brucellosis is a chronic infectious disease caused by bacteria of the genus Brucella. This disease affects many species of animals, resulting in great economic losses, and is therefore an important bacterial zoonotic disease worldwide (1). The genus Brucella replicates inside trophoblasts, macrophages, and dendritic cells and colonizes the reticuloendothelial system and reproductive organs (2). Additionally, brucellosis is not only the major cause of abortion and infertility in animals but also a debilitating disease in humans (2-7).To overcome the immune system and establish a chronic infection, B. abortus utilizes diverse evasion mechanisms. This pathogen can penetrate host cells through lipid rafts (8). Once inside cells, the establishment of a persistent infection relies on the ability of the bacterium to form a Brucella-containing vacuole (BCV), which traffics from the endocytic compartment to the endoplasmic reticulum (ER), forming a replicative BCV. It is in this replicative BCV that the bacteria begin to multiply (8, 9).Extensive vaccination programs have been undertaken to prevent brucellosis in animals. Despite their availability, live vaccine strains have critical disadvantages (10). The main vaccines currently available for brucellosis are S19 and RB51 (derived from B. abortus)...

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Section: Resultsmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

“…Three days after seeding, another 0.1 ml of LCCM was added. On the 7th day, the medium was renewed, and on the 10th day, the cells were completely differentiated into macrophages (21).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice

et al. 2015

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Progress in Brucella vaccine development

et al. 2012

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Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines.

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First Argentine database for the accurate identification of Brucella to species level by MALDI-TOF MS

Celestino,

Rocca,

Ayala

et al. 2023

Acta Tropica

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TheBrucella abortusPhosphoglycerate Kinase Mutant Is Highly Attenuated and Induces Protection Superior to That of Vaccine Strain 19 in Immunocompromised and Immunocompetent Mice

Abstract: Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals

Cited by 37 publications

References 39 publications

Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice

Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice

Progress in Brucella vaccine development

First Argentine database for the accurate identification of Brucella to species level by MALDI-TOF MS

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