<i>Brucella neotomae</i>
            Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model

Kang, Yoon‐Suk; Brown, D. A.

doi:10.1128/iai.00255-18

Cited by 12 publications

(11 citation statements)

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“…The correct identification of this species was only possible by detailed phenotypic and genotypic analysis, including WGS [ 78 ]. After these reports, investigators confirmed the infective potential of B. neotomae in mice [ 80 , 81 ]. Another example of misidentification was the Brucella sp.…”

Section: Expanding the Number Of Brucella Specimentioning

confidence: 97%

Brucella Genomics: Macro and Micro Evolution

Suárez-Esquivel

Chaves-Olarte

Moreno

et al. 2020

IJMS

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Brucella organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of the most intriguing aspects of the brucellae is that the various species show a ~97% similarity at the genome level. Still, the distinct Brucella species display different host preferences, zoonotic risk, and virulence. After 133 years of research, there are many aspects of the Brucella biology that remain poorly understood, such as host adaptation and virulence mechanisms. A strategy to understand these characteristics focuses on the relationship between the genomic diversity and host preference of the various Brucella species. Pseudogenization, genome reduction, single nucleotide polymorphism variation, number of tandem repeats, and mobile genetic elements are unveiled markers for host adaptation and virulence. Understanding the mechanisms of genome variability in the Brucella genus is relevant to comprehend the emergence of pathogens.

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Section: Expanding the Number Of Brucella Specimentioning

confidence: 97%

Brucella Genomics: Macro and Micro Evolution

Suárez-Esquivel

Chaves-Olarte

Moreno

et al. 2020

IJMS

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“…Cell culture is widely used as a representative model for microorganism’s infectivity and is especially important in helping predict the range of pathogenicity of atypical Brucella species [16, 35–37]. Invasion and replication in epithelial cells and macrophages are vital in Brucella infections, although they are just one aspect to virulence [16, 37]. Other aspects important to virulence are the type IV secretion system and the LPS O-side chain [11, 13, 23, 35, 36].…”

Section: Discussionmentioning

confidence: 99%

“…melitensis , suggests that B . neotomae possesses the ability to behave in a similar manor to the classic virulent species [9,12–16]. Since its discovery over 50 years ago B .…”

Section: Introductionmentioning

confidence: 99%

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Intracellular invasion and survival of Brucella neotomae, another possible zoonotic Brucella species

Waldrop

Sriranganathan

2019

PLoS ONE

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In 1967, Brucella neotomae was first isolated from Neotoma lepida , the dessert wood rat, in Utah. With little infection data since its discovery, the zoonotic potential of this Brucella species is largely unknown. Recent reports of isolation from human cerebrospinal fluid, along with current literature suggest that B . neotomae has the ability to infect various hosts and cell types. In this report we extend the knowledge of B . neotomae ATCC 23459’s intracellular invasion and survival abilities to a variety of cell lines through gentamicin protection assays. Some of the phagocytic and epithelial cell lines from various mammalian species represent characteristics of some cell types that could be encountered by Brucella in potential hosts. It was found that B . neotomae ATCC 23459 exhibits generally lower intracellular bacterial CFUs compared to the mouse-passaged strain of B . neotomae ATCC 23459, B . suis 1330, and B . abortus 2308. Ultimately, these observations provide a small piece of the puzzle in the investigation of the breadth of B . neotomae ’s pathogenic potential.

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“…B. neotomae, which natively infects desert pack rats, is highly related to select-agent Brucella species (B. melitensis, B. abortus, and B. suis) and also shares similar host cell infection dynamics and type IV secretion system-dependent intracellular replication and pathogenesis (5,13). However, in contrast to B. melitensis, B. abortus, and B. suis, it is not a select agent and is categorized as a biosafety level 2 pathogen, making it a useful model for highthroughput experiments.…”

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confidence: 99%

A Chemical Genetics Screen Reveals Influence of p38 Mitogen-Activated Protein Kinase and Autophagy on Phagosome Development and Intracellular Replication of Brucella neotomae in Macrophages

Kang

2019

Infect Immun

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Brucella is an intracellular bacterial pathogen that causes chronic systemic infection in domesticated livestock and poses a zoonotic infectious risk to humans. The virulence of Brucella is critically dependent on its ability to replicate and survive within host macrophages. Brucella modulates host physiological pathways and cell biology in order to establish a productive intracellular replicative niche. Conversely, the host cell presumably activates pathways that limit infection. To identify host pathways contributing to this yin and yang during host cell infection, we performed a high-throughput chemical genetics screen of known inhibitors and agonists of host cell targets to identify host factors that contribute to intracellular growth of the model pathogen Brucella neotomae. Using this approach, we identified the p38 mitogen-activated protein (MAP) kinase pathway and autophagy machinery as both a linchpin and an Achilles' heel in B. neotomae's ability to coopt host cell machinery and replicate within macrophages. Specifically, B. neotomae induced p38 MAP kinase phosphorylation and autophagy in a type IV secretion systemdependent fashion. Both p38 MAP kinase stimulation and an intact autophagy machinery in turn were required for phagosome maturation and intracellular replication. These findings contrasted with those for Legionella pneumophila, where chemical inhibition of the p38 MAP kinase pathway and autophagy factor depletion failed to block intracellular replication. Therefore, results from a chemical genetics screen suggest that intersections of the MAP kinase pathways and autophagy machinery are critical components of Brucella's intracellular life cycle. B rucella is a facultative, intracellular, Gram-negative pathogen that causes chronic systemic infection in mammals. Humans become infected through ingestion of contaminated milk, percutaneous blood exposure, or inhalation of aerosolized organisms from birthing farm animals. Infection is associated with prolonged and debilitating fever, hepatosplenomegaly, lymphadenopathy, and potentially life-threatening sequelae, including endocarditis, osteomyelitis, and meningitis (1).The VirB-based type IV secretion system (T4SS) is a major virulence determinant of Brucella spp. (2-5) and is required for intracellular replication in host macrophages. VirB mutants also show dramatically reduced virulence in experimental models. The VirB operon encodes a multiprotein molecular syringe, induced by phagosomal acidification, that translocates effector proteins from the bacterial cytoplasm across the phagosomal membrane into the host cell cytoplasm. Effectors have multiple effects on the Citation Kang Y-S, Kirby JE. 2019. A chemical genetics screen reveals influence of p38 mitogen-activated protein kinase and autophagy on phagosome development and intracellular replication of Brucella neotomae in macrophages. Infect Immun 87:e00044-19.on July 10, 2020 by guest http://iai.asm.org/ Downloaded from host cell that ultimately result in altered maturation of the bacterial phago...

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Brucella neotomae Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model

Cited by 12 publications

References 50 publications

Brucella Genomics: Macro and Micro Evolution

Brucella Genomics: Macro and Micro Evolution

Intracellular invasion and survival of Brucella neotomae, another possible zoonotic Brucella species

A Chemical Genetics Screen Reveals Influence of p38 Mitogen-Activated Protein Kinase and Autophagy on Phagosome Development and Intracellular Replication of Brucella neotomae in Macrophages

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