Mucispirillum schaedleri

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1. Classification

a. Higher order taxa

Bacteria; Deferribacterota; Deferribacteres; Deferribacterales; Deferribacteraceae [1].

b.Species

There is only one known species of the Mucispirillum, called Mucispirillum schaedleri.

2. Description and significance

Mucispirillum schaedleri is a bacteria that can pose a threat to the host’s mucous layers of the colon or cecum, causing potential health complications in animals and humans. It can be found in the gut and cause intestinal disorders. Horizontal gene transfer has had a major impact on M. schaedleri's genome, highlighting its significance in determining the bacterium's function within the gut environment [2]. Mucispirillum schaedleri plays an important role in the understanding of gut inflammation [3], with the majority of studies having been conducted on rodents and mice.

3. Genome structure

M. schaedleri's genome consists of 2.3 million base pairs with 31.15% GC content and 88% Protein coding region. The average coding sequence (CDS) length is 923.71 base pairs (bp), and the intergenic regions have an average length of 147.5 bp. Among these, there are a total of 2,227 CDS, encompassing 2,223 protein-coding genes. Additionally, the genome have 2 copies of 5S rRNA, 3 copies of 16S rRNA, and 2 copies of 23S rRNA, contributing to the ribosomal RNA content. A complete set of 39 tRNA genes has been identified, indicating the presence of a functional translation apparatus. Based on the recent genomic study, M. schaedleri’s genome possesses the genes of several pathways that are capable of utilizing monosaccharides, oligopeptides, amino acids, glycerol, and short-chain fatty acids (SCFAs) to generate energy [2]. Results showed that the genome is shaped by horizontal gene transfer, particularly from intestinal Epsilon- and Deltaproteobacteria. These intestinal components have been linked to the most prevalent cause of human gastroenteritis, suggesting that horizontal gene transfer has a significant influence in shaping its role in the gut environment with the help of effector proteins [2].

4. Cell structure

M. schaedleri is a Gram-negative, spiral-shaped anaerobe that does not form spores and is flagellated to help it pass through the layer of mucus in the gut [2]. One of the most interesting features of the cell structure is how long the flagellum is, making the microbe appear to have a long tail connected to the cell wall. This shape allows the microbe to antagonize competing cells and potentially pathogens, as well as aid in invading other cells. M. schaedleri produces spherical bodies similar to spirochetes and has a biofilm appearance that is similar to mycobacteria cording [4].

5. Metabolic processes

With its inhabitance of the mammalian gut, M. schaedleri is a chemoorganoheterotroph that utilizes anaerobic respiration of different substrates as its energy source. Based on genomic prediction, monosaccharides, oligopeptides, amino acids, glycerol, and short-chain fatty acids (SCFAs) are the preferred substrates for M. schaedleri energy metabolism [2]. Despite inhabiting the mucus layer (which is full of glycoprotein), M. schaedleri lacks the specialized glycan-degrading enzyme that is needed to degrade the host-derived glycan and utilize it as a dietary polysaccharide [2]. M. schaedleri also depends on H2 produced from other fermentative species in the gut [2]. During the host’s inflammation with increased levels of nitrate from the oxidative burst, M. schaedleri can also use the nitrate as the electron acceptor in their anaerobic respiration with fumarate [2]. M. schaedleri’s ability to use nitrate, which is abundant during inflammation, might explain why it can thrive in inflammatory conditions [8].

6. Ecology

M. schaedleri is an important microbe in the mammalian gut microbiota, especially in the intestinal tract, where the microbiota are strictly regulated by the host immune system. In immune cell-deficient mice, Mucispirillum schaedleri along with other gut microbes are found in higher concentrations (5). M. schaedleri can inhibit the growth of antagonizing Salmonella in the gut through competition for anaerobic electron acceptors. M. schaedleri’s inhibition against Salmonella reduces its ability to cause disease and protect the host gut indirectly [3]. M. schaedleri can also play an active role in the host physiology. An increased level of M. schaedleri has been associated with reducing the level of GABA, the neurotransmitter in part of the brain, emphasizing the role of M. schaedleri in the gut-brain axis [6]. Moreover, M. schaedleri is also found to directly influence the host’s brain through the secretion of plasma metabolite, inducing the reduction of bone mineral density ([7].

7. Pathology

M. schaedleri has been studied in mouse models and is related to inflammatory bowel disease (IBD) and other similar conditions ([8]. Higher levels of M. schaedleri exist in intestinal samples of guts with inflammation, colitis (a chronic digestive disorder), and infection. In addition, higher levels of the microorganism is connected to high-fat diets, stress, and diseases like Rheumatoid Arthritis and Parkinson’s Disease [8]. M. schaedleri is able to use nitrate, which is abundant during inflammation, in metabolism. This may be why the bacteria thrives in inflammatory conditions [8]. Its ability to metabolize nitrate is also why M. schaedleri can protect against Salmonella enterica serovar Typhimurium-induced colitis. This occurs in immunocompetent hosts as M. schaedleri outcompetes S. enterica for nitrate. However, in immunodeficient hosts, M. schaedleri can trigger Crohn’s disease-like colitis [8]. A study by Caruso et al. (2022) produced similar results, concluding that mice with an accumulation of M. schaedleri in their guts developed Crohn’s disease-like colitis. NOD2 is a gene related to susceptibility to Crohn’s disease (CD) and its abnormal expression resulted in inflammation, an accumulation of M. schaedleri, and ultimately CD-like colitis [9]. Although M. schaedleri is most commonly related to inflammatory intestinal issues, some studies suggest that it is linked to other unrelated conditions. M. schaedleri has been linked to Rheumatoid Arthritis, Parkinson’s Disease, and postpartum depression in mouse models (8, 9). A study by Tian et al. (2021) examined 919 TJ, a Chinese herbal medicine, as a treatment for postpartum depression. In this study, M. schaedleri was stated to be negatively correlated to GABA levels in the hippocampus. This could mean that there is a possible link between M. schaedleri and the development of postpartum depression [6].

8. Current Research

Research on Mucispirillum schaedleri in the gut mostly includes mouse and rodent models. Some studies have found that M. schaedleri helps block oxygen that Salmonella grows and thrives in (3). Additionally, research shows that M. schaedleri causes NOD2 (nucleotide-binding oligomerization domain containing 2) and CYBB (Cytochrome B-245 Beta Chain) deficiency. This resulted in Mucispirillum buildup, which was related to decreased neutrophil recruitment and bacterial killing by luminal neutrophils. The findings show that M. schaedleri causes CD-like illness when innate immunity fails to eliminate the bacterium (9).

9. References

1. [Schoch, C. L., Ciufo, S., Domrachev, M., Hotton, C. L., Kannan, S., Khovanskaya, R., Leipe, D., Mcveigh, R., O'Neill, K., Robbertse, B., Sharma, S., Soussov, V., Sullivan, J. P., Sun, L., Turner, S., & Karsch-Mizrachi, I. (2020). NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database : the journal of biological databases and curation, 2020, baaa062. <https://doi.org/10.1093/database/baaa062.>

[2][Loy, A., Pfann, C., Steinberger M., Hanson, B., Herp, S., Brugiroux, S., Neto, J.C.G., Boekschoten, M.V., Schwab, C., Urich, T., Ramer-Tait, A.E., Rattei, T., Stecher, B., Berry, D. (2017). Lifestyle and horizontal gene transfer-mediated evolution of Mucisprillium schaedleri, a core member of the murine gut microbiota. American Society for Microbiology, 2(1). https://doi-org.ezproxy.bu.edu/10.1128/msystems.00171-16.]

[3][Herp, S., Brugiroux, S., Garzetti, D., Ring, D., Jochum, L. M., Beutler, M., Eberl, C., Hussain, S., Walter, S., Gerlach, R. G., Ruscheweyh, H. J., Huson, D., Sellin, M. E., Slack, E., Hanson, B., Loy, A., Baines, J. F., Rausch, P., Basic, M., . . . Stecher, B. (2019). Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis. Cell Host & Microbe, 25(5), 681-694.e8. 10.1016/j.chom.2019.03.004]

[4][Desjardins, A., Zerfas, P., Filion, D., Palmer, R. J., Jr, & Falcone, E. L. (2023). Mucispirillum schaedleri: Biofilm Architecture and Age-Dependent Pleomorphy. Microorganisms, 11(9), 2200. https://doi.org/10.3390/microorganisms11092200]

[5][Gu, M., Samuelson, D. R., de la Rua, N. M., Charles, T. P., Taylor, C. M., Luo, M., Siggins, R. W., Shellito, J. E., & Welsh, D. A. (2022). Host innate and adaptive immunity shapes the gut microbiota biogeography. Microbiology and Immunology, 66(6), 330-341. 10.1111/1348-0421.12963]

[6][Tian, X. Y., Xing, J. W., Zheng, Q. Q., & Gao, P. F. (2021). 919 Syrup Alleviates Postpartum Depression by Modulating the Structure and Metabolism of Gut Microbes and Affecting the Function of the Hippocampal GABA/Glutamate System. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.694443]

[7][Wan, X., Eguchi, A., Chang, L., Mori, C., & Hashimoto, K. (2023). Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut–microbiota–bone–brain axis. In Neuropharmacology (Vol. 228). Elsevier Ltd. https://doi.org/10.1016/j.neuropharm.2023.109466]

Herp, S., Durai Raj, A. C., Salvado Silva, M., Woelfel, S., & Stecher, B. (2021). The human symbiont Mucispirillum schaedleri: causality in health and disease. Medical Microbiology and Immunology, 210(4), 173-179. 10.1007/s00430-021-00702-9

Caruso, R., Mathes, T., Martens, E. C., Kamada, N., Nusrat, A., Inohara, N., & Núñez, G., (2022). A specific gene-microbe interaction drives the development of Crohn’s disease–like colitis in mice. American Association for the Advancement of Science (AAAS), 4(34). 10.1126/sciimmunol.aaw4341

Qian, M., Hu, H., Yao, Y., Zhao, D., Wang, S., Pan, C., Duan, X., Gao, Y., Liu, J., Zhang, Y., Yang, S., Qi, L., & Wang, L. (2020). Coordinated changes of gut microbiome and lipidome differentiates nonalcoholic steatohepatitis (NASH) from isolated steatosis. Liver International, 40(3), 622-637. 10.1111/liv.14316

Lee, J., Jang, J., Kwon, M., Lim, S. K., Kim, N., Lee, J., Park, H. K., Yun, M., Shin, M., Jo, H. E., Oh, Y. J., Ryu, B. H., Ko, M. Y., Joo, W., & Choi, H. (2018). Mixture of Two Lactobacillus plantarum Strains Modulates the Gut Microbiota Structure and Regulatory T Cell Response in Diet-Induced Obese Mice. Molecular Nutrition & Food Research,

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