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Brevibacterium

Brevibacterium is a of Gram-positive, nonmotile, non-spore-forming in the family Brevibacteriaceae, phylum Actinobacteria, characterized by irregular rod-shaped cells that undergo a distinct rod-to-coccus growth cycle. These strictly aerobic, halotolerant organisms possess a high DNA G+C content (58–71 mol%) and are notable for their ecological roles in food fermentation, particularly , as well as their presence as commensals on and in diverse environmental niches. Morphologically, Brevibacterium species appear as slender, irregular rods measuring 0.6–1.2 μm in width and 1.5–6 μm in length, and they are non-acid-fast and catalase-positive. Physiologically, they thrive in a temperature range of 4–42°C with an optimum of 20–35°C (up to 37°C for human-associated isolates), at levels from 5.5 to 9.5, and demonstrate tolerance to high concentrations. Key metabolic traits include the production of from L-methionine, which contributes to distinctive sulfurous aromas, and the ability to degrade proteins and . Genomically, strains exhibit size heterogeneity from 2.3 to 4.5 Mbp, with cheese-adapted isolates averaging around 4 Mbp and featuring genes for osmotolerance (e.g., biosynthesis), iron acquisition via siderophores, and production. The encompasses 41 recognized , identified through 16S rRNA sequencing and DNA-DNA hybridization, with notable members including the B. linens, B. aurantiacum, and B. casei. Ecologically, Brevibacterium inhabits dairy products, , marine environments, , mural paintings, and the skin of humans and animals, where it influences microbial communities through compounds like linecin A and linocin M18 that inhibit pathogens such as and . In industry, these bacteria are crucial for surface-ripened cheeses like and , where they drive development via volatile sulfur compounds, fatty acids, and carotenoid pigments (e.g., isorenieratene) for rind coloration, while also enhancing texture through enzymatic activity. Some strains are utilized in for producing enhancers, such as for . Although primarily non-pathogenic, certain Brevibacterium species, particularly B. casei, can cause opportunistic infections in immunocompromised patients, including catheter-related bacteremia, , , and , often requiring treatment due to resistance to β-lactams and fluoroquinolones. Additionally, skin-colonizing strains contribute to by metabolizing sweat components into volatile odorous compounds. Comparative genomic studies reveal two major phylogenetic lineages, with evidence of enhancing adaptations to cheese habitats, underscoring the genus's metabolic versatility and environmental resilience.

Taxonomy

Etymology and history

The genus name Brevibacterium derives from the Latin adjective brevis, meaning short, and the Neolatin neuter noun bacterium (from Greek bakterion, small rod), alluding to the characteristically short, rod-shaped morphology of its members. The genus was formally established in 1953 by Robert S. Breed in the seventh edition of Bergey's Manual of Determinative Bacteriology, where it was proposed as a new genus to accommodate certain Gram-positive, non-spore-forming rods previously scattered among other taxa. The type species, Brevibacterium linens, originated from earlier work by Wolff, who isolated and described it as Bacterium linens in 1910 from the surface microflora of ripening Limburger cheese. This description built on prior observations of similar organisms in dairy environments by researchers like Karl Weigmann, who had identified an "organism IX" in cheese studies around 1900. Initial isolations of Brevibacterium species occurred primarily from sources, such as , , and surface-ripened cheeses, during the early , with B. linens recognized for its association with smear-ripened varieties like and . The name Bacterium linens was retained until Breed's reclassification, and the genus was officially validated under the International Code of Nomenclature in the Approved Lists of Bacterial Names published in 1980, which confirmed B. linens as the . Following its creation, the genus served as a repository for diverse coryneform bacteria, leading to taxonomic revisions in the 1960s through 1980s based on phenotypic traits such as cell morphology, pigmentation, and biochemical reactions; these efforts, including emendations by Collins et al. in 1980, restricted the genus to a more phylogenetically coherent group, reclassifying several misplaced species to other genera like Corynebacterium and Microbacterium.

Classification and phylogeny

Brevibacterium is classified within the domain Bacteria, phylum Actinomycetota, class Actinobacteria, order Brevibacteriales, family Brevibacteriaceae, and genus Brevibacterium. This hierarchical placement reflects its position among Gram-positive, high G+C content bacteria, with the family Brevibacteriaceae originally proposed by Breed in 1953 and subsequently emended based on molecular data, including the establishment of the order Brevibacteriales in 2020 (Salam et al.). As of 2025, the genus encompasses 41 validly named species. Phylogenetic studies utilizing 16S rRNA sequences position the genus Brevibacterium firmly within the Actinobacteria, where it forms a distinct closely related to genera such as Corynebacterium and Dietzia. These analyses highlight shared evolutionary traits, including irregular rod-shaped and adaptation to diverse environments, supported by sequence similarities exceeding 95% in conserved regions. The DNA of Brevibacterium species typically exhibits a high G+C content of 60–70 mol%, a hallmark of the Actinomycetota that aids in distinguishing it from lower G+C Gram-positive lineages. Taxonomic reclassifications in the , driven by 16S rRNA-based , shifted Brevibacterium from the broader Actinomycetales to Micrococcales, better aligning it with molecularly coherent groups like the suborder Micrococcineae. This adjustment, proposed by Stackebrandt et al. in 1997, refined the understanding of actinobacterial diversity by emphasizing genomic and ribosomal evidence over phenotypic traits alone. A further update in 2020 reclassified it to the Brevibacteriales. The itself was formally established by Breed in to accommodate short, non-spore-forming rods previously scattered across coryneform classifications.

Description

Morphology

Brevibacterium are Gram-positive, non-spore-forming characterized by irregular rod-shaped cells, often described as coryneform or club-shaped. These cells typically measure 0.6–1.2 μm in diameter and 1.5–6.0 μm in length, exhibiting variability in form during growth, including a rod-to-coccus transition in older cultures. They frequently arrange in palisades, pairs, or angled V- and Y-shaped configurations, sometimes referred to as "Chinese letters," a feature common to coryneform . The of Brevibacterium is composed of a thick layer diagnostic of , featuring meso-diaminopimelic acid as the diamino acid in a directly cross-linked A1γ-type structure. This composition contributes to the retention of during Gram staining, resulting in a positive reaction, while the absence of mycolic acids renders the cells non-acid-fast. On solid under aerobic conditions, Brevibacterium produces small, circular to irregular colonies measuring 0.5–2.0 mm in after 24–48 hours of . These colonies are convex, opaque, and range from smooth and shiny to rough in texture, often displaying yellow to orange pigmentation due to the accumulation of compounds such as isorenieratene and dehydrogenated derivatives. The coloration intensity can vary by strain and environmental factors, shifting from cream-yellow in young cultures to deeper orange-red tones with prolonged growth or light exposure.

Physiology and biochemistry

Brevibacterium are strictly aerobic, chemoorganotrophic that exhibit oxidative . They grow optimally at temperatures between 20°C and 30°C for environmental and food-associated strains, with some isolates tolerating up to 37°C, and a broader growth range of 8–42°C. Optimal is 6.5–8.5, with tolerance from 5.5–9.5, and they are halotolerant, growing in with up to 20% NaCl, though many strains prefer around 5%. These utilize a variety of carbon sources, including glucose and for energy, as well as such as L-methionine and , which support growth and contribute to metabolic processes like . They produce small amounts of acid from carbohydrate fermentation but do not generate gas. Their metabolism emphasizes catabolism and , enabling survival under nutrient-limited conditions through low endogenous metabolic rates and slow growth. Biochemically, Brevibacterium species are catalase-positive and oxidase-negative, aiding in their identification. activity is variable across species, as is reduction, which ranges from negative to weakly positive. The DNA base composition shows a high % G+C content, typically 59–72%, characteristic of the Actinobacteria phylum. Key enzymes include and (such as esterase C4 and esterase lipase C8), which facilitate of phosphates and . Certain species produce sulfur-containing volatiles, notably from L-methionine, contributing to their ecological roles.

Habitat and ecology

Natural distribution

Brevibacterium species are widely distributed in terrestrial environments, particularly in soils across diverse ecosystems. They are commonly isolated from arable, forest, saline, and desert soils globally, including regions such as the Sahara and Gibson deserts, where they contribute to microbial communities adapted to arid conditions. In these habitats, Brevibacterium plays roles in nutrient cycling, including nitrogen fixation and phosphate solubilization, which support soil fertility and ecosystem processes. Aquatic and marine habitats also harbor Brevibacterium, with isolations reported from , deep-sea sediments, and freshwater systems. For instance, species such as Brevibacterium oceani and Brevibacterium sediminis have been recovered from deep-sea sediments in the and Carlsberg Ridge, respectively, demonstrating adaptation to high-pressure and saline conditions. Some species display halophilic or halotolerant traits, enabling persistence in high-salinity environments like sediments and coastal areas. Brevibacterium is frequently associated with , occurring on surfaces and in rhizospheres of various species, including and heavy metal-contaminated sites. In these niches, strains such as Brevibacterium casei promote plant growth through production, which enhances iron acquisition, alongside other mechanisms like acetic acid synthesis. Overall, Brevibacterium exhibits global ubiquity in natural environments but typically at low abundance within microbial communities. Culture-independent methods, such as , have detected the genus in soils, aquatic systems, and rhizospheres across multiple continents, underscoring its widespread yet non-dominant presence.

Associations with environments

Brevibacterium species are prevalent in processing environments, particularly on the rinds of surface-ripened cheeses where they form part of complex microbial consortia alongside like Arthrobacter and fungi such as . These contribute to the maturation process by colonizing cheese surfaces during , with species like and B. aurantiacum emerging dominantly in washed-rind varieties. In fermented foods beyond , Brevibacterium strains participate in microbial communities that influence product development, often originating from facility-specific environments. As commensal members of the , Brevibacterium species, including B. epidermidis and B. casei, are commonly found in moist areas such as the feet, where they contribute to production through metabolic activities. They are also detected in mucosal sites and occasionally in the , though less abundantly than on . In clinical settings, Brevibacterium has been isolated from human blood, wounds, and peritoneal dialysis fluids, reflecting opportunistic colonization from in immunocompromised or catheterized individuals. Brevibacterium species associate with animal-derived materials in agricultural contexts, including hides where they aid in degrading keratin-rich waste during processing. Strains like B. luteolum exhibit proteolytic activity that facilitates breakdown, supporting eco-friendly in operations. Additionally, Brevibacterium appears in animal gut microbiomes, such as in , where it may increase in abundance under certain conditions, potentially influencing microbial diversity. In polluted environments, certain Brevibacterium species demonstrate potential by degrading hydrocarbons like in oil-contaminated sites. For instance, B. sediminis isolates from petroleum-polluted areas efficiently metabolize polycyclic aromatic hydrocarbons. Other strains, such as B. casei, tolerate including lead, , and in contaminated rhizospheres and wastewaters, aiding in metal sequestration or reduction. While soil serves as a primary natural reservoir for Brevibacterium, human-modified sites amplify their ecological roles in remediation.

Applications

Role in food production

Brevibacterium linens plays a pivotal role in the ripening of surface-ripened cheeses, particularly those with washed rinds, where it colonizes the cheese surface and contributes to the degradation of proteins and fats. As a key component of the surface microflora, B. linens performs , breaking down caseins into free that serve as precursors for flavor development, and , hydrolyzing triglycerides to release free fatty acids. These metabolic activities enhance the texture and overall maturation of cheeses such as and . The bacterium is renowned for producing volatile sulfur compounds that impart the characteristic pungent, sulfurous aromas to these cheeses. Specifically, B. linens converts into and , which are essential for the distinctive foot-like odor associated with smear-ripened varieties. Additionally, its production of pigments results in the orange-red coloration of the rind, enhancing the visual appeal and authenticity of traditional cheeses. The of B. linens enables its survival and proliferation on salted cheese surfaces during the washing process. In commercial cheesemaking, B. linens strains are routinely inoculated as starter cultures to ensure consistent flavor profiles and rind development in washed-rind cheeses. Selected strains are applied directly to the or via washes to standardize the process and accelerate maturation without bitterness. These organisms are considered safe for use in food production by regulatory authorities such as the USDA. Historically, B. linens has been integral to European cheesemaking traditions since the , naturally occurring on the rinds of soft, smear-ripened cheeses like those from and , long before its formal isolation in 1910. Its role in flavor and color formation has been harnessed in artisanal practices, contributing to the sensory diversity of regional dairy products.

Industrial uses

Strains formerly classified as Brevibacterium flavum and B. lactofermentum (now Corynebacterium glutamicum) were among the first bacteria employed for industrial amino acid production in the 1960s and 1970s, with strains engineered through classical mutagenesis to overproduce L-lysine and L-threonine via fermentation processes using carbon sources like glucose or molasses. These early efforts achieved yields of up to 65 g/L of L-lysine under optimized conditions, though production later shifted toward Corynebacterium glutamicum due to its superior efficiency and genetic tractability. Metabolic engineering techniques, such as disrupting feedback inhibition in aspartate kinase and overexpressing key pathway enzymes like dihydrodipicolinate synthase, enhanced overproduction in these strains. Certain Brevibacterium isolates exhibit potential through enzymatic degradation of environmental pollutants, including sulfur-containing compounds like dibenzothiophene and hydrocarbons. For instance, Brevibacterium sp. DO utilizes dibenzothiophene as a sole carbon, , and source, cleaving the sulfur via desulfurization enzymes to produce 2-hydroxybiphenyl without ring destruction. Similarly, Brevibacterium sp. BS18 achieves up to 70% degradation of crude components in contaminated soils over 30 days, highlighting its role in microbial consortia for cleanup. Beyond amino acids, Brevibacterium strains contribute to metabolite production for pharmaceutical and antioxidant applications, notably through carotenoid biosynthesis. B. linens naturally produces pigments like isorenieratene and β-carotene, with yields varying by strain (up to 1.5 mg/g dry cell weight) and optimized via media adjustments like yeast extract supplementation. Genetic reconstruction of the crt operon in B. linens DSMZ 20426 has extended pathways to yield astaxanthin and zeaxanthin, compounds with high antioxidant activity used in nutraceuticals. Research also explores enzyme production, such as proteases from B. linens for industrial hydrolysis, though yields remain modest compared to amino acid processes. Recent genomic studies have identified biosynthetic gene clusters in Brevibacterium strains from diverse ecosystems, suggesting potential for novel production. Additionally, strains such as B. casei EB3 demonstrate applications in by enhancing rhizobacterial communities to promote plant growth. Strain development relies on genetic tools like shuttle vectors (e.g., pCB192) for introducing plasmids into Brevibacterium, enabling stable expression of genes for pathway . Techniques include for transformation efficiencies up to 10^4 transformants/μg DNA and CRISPR-based editing for precise knockouts, as demonstrated in recent studies on B. linens. These bacteria's tolerance to osmotic and high temperatures supports their viability in robust fermentations.

Clinical significance

Infections in humans

Brevibacterium species are opportunistic pathogens that primarily cause infections in immunocompromised individuals, with documented cases including bacteremia, , and , particularly in patients undergoing . These infections arise from translocation of the , which are part of the normal , often facilitated by invasive procedures such as central venous catheters or wounds. The first reported human by Brevibacterium dates back to a case of in 1969, though recognition as clinically significant pathogens increased in the with the identification of species like B. casei from clinical isolates previously classified under CDC coryneform groups. As of February 2025, 42 cases of Brevibacterium infections in humans had been documented across the literature in a narrative review, underscoring their rarity, with a patient age of 48 years and a slight predominance (57.5%). Bacteremia accounts for the majority (57.1%) of cases, frequently associated with catheter-related ; endocarditis represents 7.1% of reports, including the first documented instance in 2002 caused by B. otitidis in a with prosthetic heart valves; and peritonitis comprises 16.7%, often linked to , with an early case of B. otitidis reported in 2000. An additional case of B. ravenspurgense bacteremia was reported later in 2025 in a with . Common risk factors include the presence of central venous catheters (41.5% of cases), underlying malignancies (25%), and end-stage renal disease managed with (17.5%), highlighting the role of medical interventions in predisposing vulnerable s. Despite their low , Brevibacterium species can persist in biofilms, contributing to chronic or relapsing infections in these settings. The most frequently isolated species is B. casei (47.6% of cases), followed by B. epidermidis (7.1%), B. otitidis (7.1%), and B. sanguinis (2.4%), with isolates commonly recovered from blood, , and valvular tissue. A case of B. ravenspurgense was also reported in 2025. Diagnostic challenges stem from the morphological similarity of Brevibacterium to species, leading to frequent initial misidentifications in routine culture; accurate confirmation typically requires advanced molecular methods such as 16S rRNA gene sequencing (used in 31% of cases) or (MALDI-TOF MS, employed in 33.3%). These techniques have been essential in distinguishing Brevibacterium from more common coryneform contaminants, enabling proper recognition of its pathogenic potential in clinical contexts.

Antimicrobial susceptibility

Brevibacterium species demonstrate consistent susceptibility to , with resistance reported in only 8.1% of isolates across reviewed cases, and no instances of high-level vancomycin resistance documented to date. They also exhibit high sensitivity to , with all tested clinical isolates susceptible in multiple studies, and to tetracyclines, where resistance rates remain low at 5.3%. In contrast, resistance to is more variable, affecting 50% of isolates for penicillin and 34.8% for cephalosporins, often linked to production in strains such as B. casei and B. ravenspurgense. Resistance mechanisms primarily involve intrinsic low-level tolerance to certain agents and enzymatic inactivation via beta-lactamases, which hydrolyze penicillin and cephalosporins in susceptible strains; acquired resistance through mobile elements like plasmids appears rare in clinical contexts. Minimum inhibitory concentrations (s) from susceptibility testing underscore this profile, with MIC<sub>90</sub> values typically below 4 μg/mL for (≤0.5 μg/mL), (1-2 μg/mL), tetracyclines (≤4 μg/mL), and like (≤0.5 μg/mL), while beta-lactams show elevated MICs in resistant cases (e.g., penicillin MIC 0.5-8 μg/mL, intermediate to resistant). Treatment guidelines recommend empirical therapy with glycopeptides such as for severe Brevibacterium , particularly in immunocompromised patients, pending susceptibility results to guide . Clinical outcomes are favorable, with cure rates exceeding 90% when appropriate antibiotics are administered promptly; reported mortality is low at 10.3% overall (7.7% attributable to ) in case series up to 2025, emphasizing the importance of and .
Antibiotic ClassExample AgentsTypical SusceptibilityRepresentative MIC<sub>90</sub> (μg/mL)Notes
GlycopeptidesHigh (>90%)≤1Empirical choice; no resistance reported.
OxazolidinonesHigh (100%)1-2Reliable alternative for Gram-positive coverage.
TetracyclinesHigh (>94%)≤4Low resistance; variable in some cases.
Beta-lactamsPenicillin, CephalosporinsVariable (35-50%)2-8 (resistant)Beta-lactamase mediated; use if needed.

Species

Type species

Brevibacterium linens serves as the type species for the genus Brevibacterium, providing the foundational reference for taxonomic classification within this group of . Originally described as Bacterium linens by Wolff in 1910 from butter and cheese surfaces, it was reclassified into the genus Brevibacterium by in 1953. The species description was emended by Collins et al. in 1980 to incorporate chemotaxonomic data, including composition and profiles, and further refined in subsequent studies during the 2000s to account for genomic insights. The type strain, 20425 (also known as ATCC 9172), was isolated from a environment and maintains the defining characteristics of the species. Morphologically, B. linens consists of irregular rods that undergo a characteristic rod-coccus growth cycle, appearing as short, club-shaped cells in young cultures and transitioning to coccoid forms in older ones; it is non-motile, non-sporeforming, and strictly aerobic. Colonies are typically yellow- to orange-pigmented due to production, and the species is notable for generating -specific volatiles, such as and , which contribute to its distinct aroma profile. This bacterium is primarily isolated from the rinds of smear-ripened cheeses, where it thrives in the surface microbial . Physiologically, B. linens exhibits strong proteolytic activity, secreting extracellular enzymes that hydrolyze caseins and other proteins into peptides and free , followed by to produce as a key metabolic end product. This generation raises the of the surrounding environment and is central to its biochemical role. Optimal growth occurs at 20–30°C, with many strains peaking around 25–28°C, and requires moderate of 5–10% NaCl, though it demonstrates up to 15% NaCl, enabling survival in saline habitats. As the for the Brevibacterium , B. linens exemplifies the group's coryneform , salt tolerance, and enzymatic capabilities, serving as a in taxonomic delineations. It is extensively employed in studies to elucidate genetic adaptations across brevibacteria, including gene clusters for pigmentation and flavor compound . In cheese production, B. linens contributes to rind coloration and volatile aroma development during .

Diversity and notable species

As of November 2025, the Brevibacterium comprises 41 validly published species, according to the List of Prokaryotic names with Standing in Nomenclature (LPSN). This diversity reflects ongoing discoveries from diverse habitats, with recent additions including B. album (validly published in 2008), B. ammoniilyticum (2013), and B. anseongense (2019). Among these, several species stand out for their ecological or . Brevibacterium casei, frequently isolated from human clinical specimens, is notable for causing opportunistic infections such as bacteremia and , particularly in immunocompromised individuals; it forms white-gray colonies on media. Brevibacterium epidermidis, a common skin commensal, contributes to the bacterial on surfaces with higher values, such as intertriginous areas, and is characterized by its aerobic growth and association with production through volatile compounds. Brevibacterium iodinum, often found in aquatic and soil environments including water and , produces distinctive purple pigments like iodinin and is implicated in rare opportunistic infections. Brevibacterium mcbrellneri, isolated from clinical sites such as infected genital hair in cases of , exhibits potential clinical relevance in superficial infections, though its pathogenicity remains understudied; it is distinguished by its Gram-positive rod morphology and isolation from fungal co-infections. Brevibacterium aurantiacum is notable for its role in cheese rind coloration due to pigments. The taxonomy of Brevibacterium has seen reclassifications and synonymies due to phylogenetic reevaluations. For instance, Brevibacterium halotolerans was reclassified as halotolerans based on phylogenomic and DNA-DNA relatedness analyses. Similarly, Brevibacterium frigoritolerans was reclassified as frigoritolerans comb. nov. based on phylogenomics and multiple molecular synapomorphies. Invalid proposals include "Brevibacterium pigmentatum" (2021), now a synonym of an unvalidly published name. Species identification within Brevibacterium relies on polyphasic , integrating genotypic methods like 16S rRNA sequencing (with similarity thresholds often below 98.7% indicating novel species) and DNA-DNA hybridization (values >70% for conspecificity), alongside phenotypic traits and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF MS) for rapid differentiation. This approach ensures robust classification amid the genus's heterogeneity.