Christensenella

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1. Classification

a. Higher order taxa

Bacteria, Firmicutes, Clostridia, Clostridiales, Christensenellaceae, Christensenella Species: Christensenella minuta, Christensenella massiliensis, Christensenella timonensis (1, 2)

2. Description and significance

Christensenella is a Gram-negative, strictly anaerobic genus of bacteria first discovered in the human gut (3). Species within this genus are bacillar (rod-shaped), non-motile and non-spore forming (3, 4, 5). Christensenella minuta, Christensenella timonensis, and Christensenella massiliensis are currently the only known species of Christensenella, all of which were isolated from human stool samples (3, 4, 5). C. minuta was first recognized as a new taxon in 2012, after a Japanese study of the human microbiome isolated a previously uncharacterized bacterial strain from a sample of human stool (3).

Christensenella in the human gut microbiome is associated with several health-promoting effects, and is believed to be strongly influenced by the genetic makeup of its host (6). As a result, it has been the focus of recent research investigating the relationship of host genetics to the development of the gut microbiome and associated implications for GI health. The presence or absence of Christensenella is thought to impact an individual’s risk of obesity. Associations with lean body type, lower BMI and reduced gain of fat tissue have highlighted possible future therapeutic uses of Christensenella (7, 8). In particular, C. minuta has been studied in obesity prevention and as a weight-loss aid (6). Christensenella is also believed to act as a keystone species (7) in the human gut, forming relationships with other bacteria which have the potential to advance scientific understanding of the role of the human gut microbiome in gastrointestinal disease (3). However, more evidence is needed in order to confirm Christensenella as a keystone species and to fully understand the structure of its genome. C. minuta is highly heritable among twins, suggesting that the human microbiome is controlled by host genetics which then indirectly influence the development of obesity and other gastrointestinal diseases through microbial pathways (6). Development of therapeutic applications for Christensenella is an area of active research (9), as are the mechanisms underlying its effects on BMI and understanding of the specific genetic elements that control its colonization of the GI tract (6).

3. Genome structure

The genomes of three known species and one unidentified strain of Christensenella have been sequenced to various assembly levels (4, 5, 10). C. massiliensis is the only species within this genus with a completely sequenced genome of 2.56 million base pairs (Mbp), 2,515 genes and 2,428 protein coding genes (5). The remaining species and strains of Christensenella have not been sequenced beyond the scaffold level (4, 10).

The genomes of taxa within the Christensenella genus are approximately 2.56 to 3.03 million base pairs (Mbp) in length and contain between 2,500 and 2,900 genes encoding between 2,403 and 2,766 proteins (4, 5, 10). Approximately 79.7% of the genome of C. minuta is comprised of functional genes (10), encoding transcription factors as well as proteins for polysaccharide biosynthesis, translation and molecular transport (1, 2). Non-coding regions of the genome are associated with tRNA, rRNA and other RNA constructs as well as several pseudogenes. Genomic GC content within this genus ranges from 50.4 to 52.1% (4, 5, 10).

As the first organism to be discovered in the Christensenella genus and the wider Christensenellaceae family, C. minuta Strain YIT 12065 is considered the founding strain of these two taxa and has served as the primary reference strain for classifying new species of Christensenella (3). Since the discovery of Strain YIT 12065, the Christensenella genus has grown to include the species C. timonensis and C. massiliensis (4, 5), which show 97.4% and 97.5% sequence similarity, respectively, with C. minuta via 16s rRNA sequencing (3, 4, 5). This degree of genetic divergence sufficiently supports their classification as novel species of Christensenella (3, 4, 5). Close relatives of Christensenella species include Caldicoprobacter oshimai (86.9% genetic concordance), Tindallia californiensis (86.3% concordance) and Clostridium ganghwense (86.1% concordance) as determined by 16s rRNA sequencing (1).

4. Cell structure

Bacteria of the Christensenella genus are short, non-motile and rod-shaped (bacillar). Single cells typically measure approx. 0.3 m x 0.8-1.9 m (3, 4, 5). C. minuta has tapered ends and may also appear in pairs with a more rounded coccobacillary shape (7). When cultured, Christensenella form circular yellow-beige colonies of 0.1-0.2 mm in diameter with a point-like appearance. Members of this genus do not form endospores (3, 4, 5).

Although Christensenella species are Gram-negative, isolates within this genus display variable Gram staining properties (7). Christensenella species were originally determined to be Gram-negative on account of the negative Gram stain observed in the initial isolate of C. minuta YIT 12065 (3). However, a Gram-positive bacterial species of similar morphology later isolated from human blood showed a 99.9% sequence similarity with C. minuta, suggesting that both Gram-positive and Gram-negative strains may exist within Christensenella and the C. minuta species (7). This variable dyeing phenomenon has also been observed among species of the order Bacillales, which similarly shows Gram-positive, Gram-negative, and Gram-variable staining. Although Christensenella is considered a Gram-negative genus, inconsistent Gram staining properties may therefore contribute to the misclassification of member species (7). LL-diaminopimelic acid, a cell wall component typically found in Gram positive bacteria, has also been identified in the cell wall of C. minuta, although this molecule has been previously observed in the cell walls of several other Gram-negative bacteria in the order Clostridiales. The cell wall of C. minuta is enriched in alanine, serine, and glutamic acid residues (3).

5. Metabolic processes

As a strictly anaerobic genus, Christensenella organisms produce energy exclusively through fermentation and contain no respiratory quinones. Bacteria of the genus Christensenella are chemoheterotrophic and saccharolytic, using glucose and other sugars including salacylin, D-xylose, L-arabinose, L-rhamnose and D-mannose as the primary energy inputs of fermentation (3). Glucose fermentation by C. minuta produces acetic acid and butyric acid. Whole-cell sugars in C. minuta include ribose, rhamnose, galactose and glucose (3). The originally characterized C. minuta strain was also capable of cellulose digestion (3). Christensenellaceae organisms are correlated with secondary bile acid metabolism (7), and may influence metabolic signaling within the human digestive system (11). C. minuta is catalase negative, oxidase negative and urease negative. It is also incapable of reducing nitrates and cannot metabolize tryptophan (3).

The role of Christensenella metabolic processes in promoting weight loss in humans is unclear, but may provide future insight into the metabolic capabilities of this genus (6).

6. Ecology

All known species of Christensenella are native to the digestive tract and have been isolated from human stool samples (3, 4, 5). Abundance of Christensenella in the gut microbiome depends on the genome of its host, as this genus shows high genetic heritability among related individuals (6). C. minuta is optimized for growth in the human digestive tract, with an optimal growth temperature of 37o-40o C (Range: 20-45o C) and an optimal pH of 7.5 (Range: 6.0 - 9.0) (3). Optimal salt concentration is roughly 1% NaCl solution. C. minuta is resistant to 20% bile (3). Heritability Christensenellaceae is a highly heritable family, meaning that similar levels of Christensenellaceae bacteria are found among related individuals, particularly twins. One study conducted at Cornell University found that microbial diversity is more similar among identical (monozygotic) compared to fraternal (dizygotic) twins, and among any twins than between two unrelated individuals (6). This effect is especially apparent for Christensenellaceae, which is present from birth. Up to 20% of species in infant stool samples collected for the study were classified as Christensenellaceae, which is a significantly higher proportion than observed in adult samples (6). As a result, the development of Christensenellaceae colonies in the gut is believed to be under the control of genes of the host individual. Christensenellaceae may therefore play a role in elucidating the effects of environmental conditions and genetic makeup on the composition of human gut microbiota and variation between individuals (6). This relationship has wide ranging implications for understanding the interdependence of genetics and the microbiome on obesity, gastrointestinal diseases and some genetic mechanisms of disease. Research into what human genes control the establishment of Christensenella is necessary to further characterize the nature and mechanisms of its relationship to its host’s genome (6). Christensenellaceae plays a role in the microbial ecology of its host and the establishment of other species within the human gut microbiome. In the human gut, the abundance of other archaeal and bacterial species is strongly associated with the presence and abundance of Christensenellaceae bacteria (6). Like Christensenellaceae, these organisms are highly heritable and may show similar linkage to the genetic makeup of the host individual. For this reason, Christensenellaceae has been proposed as a possible keystone species within the intestinal microbiome that facilitates the establishment of other microbial taxa (6).

7. Pathology

How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.

8. Current Research

Include information about how this microbe (or related microbes) are currently being studied and for what purpose

9. References

It is required that you add at least five primary research articles (in same format as the sample reference below) that corresponds to the info that you added to this page. [Sample reference] Faller, A., and Schleifer, K. "Modified Oxidase and Benzidine Tests for Separation of Staphylococci from Micrococci". Journal of Clinical Microbiology. 1981. Volume 13. p. 1031-1035.