Expanded Genus Brucella: from Taxonomy to Clinical Manifestations and Diagnosis Challenges

Historically, Malta’s fever agent was isolated from diseased British soldiers from Malta in 1886 by Sir David Bruce, and called initially Micrococcus melitensis and later Brucella melitensis, in honor to its discoverer. The disease is nowadays usually called brucellosis instead of Malta’s fever. Other species belonging to the genus Brucella have been named according to a preferential animal host during the 20th century.
The species classification was based only on phenotypic characteristics without any knowledge on their genetic or genomic diversity. Nevertheless, in the 1980s, DNA-DNA hybridization studies revealed more than 95% DNA relatedness between the species, thus suggesting that the genus actually constitute a single species, to be named B. melitensis, in agreement with the most pathogenic and prevalent strains at that time. The remaining species in this classification would constitute biogroups within this single species, with as proposed nomenclature for example B. melitensis var. Melitensis, B. melitensis var. Abortus etc. to keep an identity according to previous species classification. Despite this sound molecular basis of classification, it has not been accepted by the brucellosis scientific community.
Meanwhile a new genus was described, named Ochrobactrum, with its main representative species being Ochrobactrum anthropi causing opportunistic infections in humans. The number of species in this genus increased over time with some others causing opportunistic human infections, of which the more important Ochrobactrum intermedium, which was named after the fact that it was found to share several characteristics of the Brucella genus and according to this it was somehow situated between O. anthropi and Brucella spp. Later in the mid-2000s the genetic relatedness between Ochobactrum spp. and Brucella spp. was clearly established by molecular phylogenetic approaches such as the initial 16S rRNA and recA genetic analyses. It became clear on the basis of these analyses that members of the Brucella and Ochrobactrum genera constitute actually the same genus. The main difference in terms of species classification was that species belonging to the genus Ochrobactrum consist of true genetic species whereas Brucella not, as demonstrated before by DNA-DNA relatedness. More recently analyses based on whole genome sequences have clearly confirmed that Ochrobactrum and Brucella constitute the same genus, and the genus names of Ochrobactrum have therefore been replaced by “Brucella” in nucleotide and genome databases (e.g. NCBI), while keeping the initial species name, e.g. Brucella anthropi.
Of note is also the debate about the antimicrobial therapy of cases due to Brucella isolates in contrast to those that previously belonged to Ochrobactrum (thus now also Brucella species isolates), especially because of the intracellular persistence of Brucella species (but not the previous Ochrobactrum species). These identification issues may have led to antibiotic treatment failures and have raised even more concerns with the emergence of new brucellosis-causing organisms other than those originating from livestock. Indeed, since the years 2000s a number of new potential species has been isolated from unexpected animal sources such as amphibians or other wildlife animal species. Those isolates are genetically more distant from the classical zoonotic Brucella species, and today only one of these was given a new species name, namely Brucella inopinata isolated from a human case. Although some genetic evidence has been established between human and amphibian isolates, the actual source of human infections remains to be identified.
Of interest is also the fact that no susceptibility testing guidelines regarding Brucella spp. existed until the CLSI M45 document was published. Nevertheless, concern has been expressed regarding the nature of the media suggested in these guidelines and in that respect, work is being done by EUCAST (https://www.eucast.org/) in order to publish a set of guidelines using more appropriate media.
In the light of the new classification of the expanded genus Brucella comprising now the former opportunistic Ochrobactrum species, coupled with the work being done on the standardization process of the susceptibility testing methodology, this Research Topic aims to further extend our knowledge on members of the merged genus and more particularly in the field of human infection, clinical manifestations, pathogenesis, host-pathogen interaction, differential diagnosis (intracellular vs extracellular opportunistic infection), prevention, and treatment.

All article types of the section Infectious Agents and Disease are welcome for this Research Topic:
https://www.frontiersin.org/journals/microbiology/sections/infectious-agents-and-disease#article-types

The specific topics of the research topic are including, but are not limited to:
- Epidemiology and molecular epidemiology to trace the source of human infection
- Taxonomy and classification of new isolates
- Genetics and genomics of the expanded Brucella genus
- Surface characteristics of the cell wall and outer membrane (proteins and lipopolysaccharide)
- Clinical and pathological features in human infections
- Molecular, serological, or cellular diagnosis tests
- Pathogenesis in humans
- Animal and cellular models relevant to human infection
- Antimicrobial treatment and antimicrobial resistance and mechanisms
- New therapeutic targets to treat human infections

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Brucellosis, Brucella, Ochrobactrum, Human, Clinical, Diagnosis, Treatment, Taxonomy, Genomics, Antimicrobial resistance

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