Bacteroides thetaiotaomicron: Difference between revisions

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===Higher order taxa===
===Higher order taxa===


Bacteria; Bacteroidetes; Bacteroidetes (class); Bacteroidales; Bacteroidaceae
Bacteria; Bacteroidetes; Bacteroidetes (class); Bacteroidales; Bacteroidaceae (2)


===Species===
===Species===


Bacteroides thetaiotaomicron
''Bacteroides thetaiotaomicron''  (2)


==Description and significance==
==Description and significance==
Bacteroides thetaiotaomicron, a Gram negative anaerobic microbe, resides in and dominates the human intestinal tract . It consists of a 4776 member proteome containing the structural means to bring in and hydrolyze non-digestible polysaccharides as well as an environment sensing mechanism consisting of outer membrane proteins. Initially isolated from fecal matter, Bacteroides thetaiotaomicron has great importance in terms of the study of the symbiotic bacteria-host relationships within the human intestine as well as for its digestive abilities and potential breakdown of digested plants.
''Bacteroides thetaiotaomicron'', a Gram-negative anaerobic microbe, resides in and dominates the human intestinal tract . It consists of a 4776 member proteome containing the structural means to bring in and hydrolyze non-digestible polysaccharides as well as an environment sensing mechanism consisting of outer membrane proteins. Initially isolated from fecal matter, ''Bacteroides thetaiotaomicron'' has great importance in terms of the study of the symbiotic bacteria-host relationships within the human intestine as well as for its digestive abilities and potential breakdown of digested plants. (8) Its contributions to postnatal gut development, host physiology, and metabolic capabilities it provides the host, are among the significant benefits it relays. (13) However, it is also a key anaerobic gram-negative bacterial pathogen with extreme disease causing potential as well as antibiotic resistance, which is of clinical interest.


==Genome structure==
==Genome structure==
Bacteroides thetaiotaomicron consists of a 6.26 Mb genome containing 4776 genes that encode for 4776 proteins. The genome exists as one circular chromosome made of double stranded DNA. The GC content is 42.8% and 90% of the genome is involved in coding for proteins.  
''Bacteroides thetaiotaomicron'' consists of a 6.26 Mb genome containing 4776 protein coding genes. The genome exists as one circular chromosome made of double stranded DNA. The GC content is 42.8% and 90% of the genome is involved in coding for proteins essential in the binding and import of various polysachharides. (1,8)


Additionally, Bacteroides thetaiotaomicron consists of one circular plasmid (p5482) which is 33,038 bp long, containing 38 genes coding for 38 proteins. The GC content of the plasmid is 47.2% and 83% of the genome is involved in coding for proteins. This 33 kb plasmid is one of several types of mobile genetic elements, including 63 transposases and four homologs of the conjugative transposon CTnDOT. The broad range of CTnDOT hosts as well as presence of CTn leads to the theory that microevolution could occur by means of DNA transfer between B. thetaiotaomicron and other forms of bacteria residing in the human gut.
Additionally, ''Bacteroides thetaiotaomicron'' consists of one circular plasmid (p5482) which is 33,038 bp long, containing 38 genes coding for 38 proteins which function mainly in environmental sensing. The GC content of the plasmid is 47.2% and 83% of the genome is involved in coding for proteins. [1] This 33 kb plasmid is one of several types of mobile genetic elements, including 63 transposases and four homologs of the conjugative transposon CTnDOT. The broad range of CTnDOT hosts as well as presence of CTn leads to the theory that microevolution could occur by means of DNA transfer between ''B. thetaiotaomicron'' and other forms of bacteria residing in the human gut. (8)


Another interesting feature of B. thetaiotaomicron is that a large portion of its genome is involved in the harvesting and metabolizing of dietary polysaccharides. The co-localization of these genes involved in polysaccharide metabolism along with ECF-type sigma factors (important in sensing envoronmental cues) allow B. thetaiotaomicron to coordinate nutrient availability with expression of these specific genes.
Another interesting feature of ''B. thetaiotaomicron'' is that a large portion of its genome is involved in the harvesting and metabolizing of dietary polysaccharides. The co-localization of these genes involved in polysaccharide metabolism along with ECF-type sigma factors (important in sensing envoronmental cues) allow ''B. thetaiotaomicron'' to coordinate nutrient availability with expression of these specific genes. (8)


==Cell structure and metabolism==
==Cell structure and metabolism==
Bacteroides thetaiotaomicron is an anaerobic obligate parasite, which utilizes polysaccharides as its source of carbon and energy. An important step in the metabolism of the polysaccharide entails its binding to the cell surface before undergoing hydrolysis. This allows for the efficient sequesteration of hydrolysis products. Cell associated enzymes are responsible for hydrolyzing the polysaccharides into small fragments which are easily digestible. This binding and cleavage of the large substrate occurs either before or during translocation into the periplasm. The outer membrane associated multi-protein complex involved in this digestion process separates substrate binding and hydrolysis using different proteins for each task.
''Bacteroides thetaiotaomicron'' is an obligate anaerobe, a major endosymbiont of the human gut. The bacterium uses various polysaccharides as its source of carbon and energy. ''B. thetaiotaomicron'' is able to use amylose, amylopectin, and pullulan (all three forms of starch) in addition to  maltooligosaccharides. (9) Thus, the organism digests complex plant materials that human enzymes cannot, and it makes an important contribution to human caloric. <br>
A key step in the metabolism of the polysaccharides entails their binding to the cell surface before undergoing hydrolysis. This allows for the efficient sequestration of hydrolysis products. Cell associated enzymes are responsible for hydrolyzing the polysaccharides into small fragments which are easily digestible. This binding and cleavage of the large substrate occurs either before or during translocation into the periplasm. The outer membrane-associated multi-protein complex involved in this digestion process separates substrate binding and hydrolysis using different proteins for each task. (7)
 
The specific starch utilization system of ''B. thetaiotaomicron'' consists of a structure of seven ''sus'' (starch utilization genes) structural genes (''susA'' to ''susG''). Most of these genes encode proteins involved in the binding and hydrolysis of starch, and are separated into two transcriptional segments (''susA'' and ''susB'' to ''susG'' respectively). Maltose as well as higher oligomers of starch are important in regulating structural gene expression, as the ''sus'' structural genes are only expressed in their presence. The expression of ''sus'' genes is regulated by the regulatory proteins SusR and MalR, which are both always expressed regardless of environmental cues. These two regulons make up for all of the genes needed to grow on starch and maltotriose. (10)


==Ecology==
==Ecology==
Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.
''Bacteroides thetaiotaomicron'' is a major component of the adult intestine and has been used as a useful model for the study of human-bacterial symbiosis. Its metabolic function for humans is to degrade plant polysacharides, a very essential capability for the human gut. Additionally, it is very important during the postnatal transition between mother's milk and a diet heavily consisting of plant starches. It has been found to stimulate angiogenesis (growth of new blood vessels from pre-existing vessels) within the gut, due to a microbial signal via bacterial sensing Paneth cells. ''B. thetaiotaomicron'' benefits its host by providing sufficient absorptive ability for nutrients the microbe helps process. Another postnatal developmental process within the gut mediated by ''Bacteroides thetaiotaomicron'' is the formation of the intestinal mucosal barrier, which helps protect the host against pathogenic invasion via the regulation of the expression of species-specific protein antibiotics. (13)
 
The environment sensing regulatory apparatus present in ''B. thetaiotaomicron'' allows for adaptive food seeking, which stabilizes food webs, and subsequently leads to the longevity of communities. (13) This ability to adaptively 'forage' is an area of biotechnical interest. (14)


==Pathology==
==Pathology==
How does this organism cause disease? Human, animal, plant hosts?  Virulence factors, as well as patient symptoms.
''Bacteroides thetaiotaomicron'' is the second most common infectious anaerobic gram-negative bacteria. It is considered an opportunistic  pathogen, frequently associated with peritonitis, septicemia, and wound infections. ''B. thetaiotaomicron'' is capable of causing very serious infections, such as intra-abdominal sepsis and bacteremia. It's resistance to antimicrobial agents is a cause for major concern, and thus methods to identify ''B. thetaiotaomicron'' in clinical specimens is of utmost importance. (11)
 
The many self-transmissable and mobile genetic elements carried by ''B. thetaiotaomicron'' are seen as the likely culprits for the spread of antibiotic resistance genes. Antibiotic resistance genes have been found on conjugative transposons ('integrated DNA elements that excise themselves to form a covalently closed circular intermediate') (12), as well as on conjugative and mobilizable plasmids (circular, self-replicating DNA molecule). (12)
 
Anaerobes in general can cause infection whenever they invade a sterile fluid or tissue environment, such as cerebrospinal fluid. An example of such an event relating to the ''Bacteroides'' genus is ''Bacteroides'' meningitis, which has been identified in patients with digestive bacterial proliferation making its way to the subarachnoidal space as well as in patients following the spread of ear infections. The ''Bacteroides'' genus provides the main agents of anaerobic meningitis, however fewer than 100 cases of ''Bacteroides'' meningitis have been reported in English literature, and they are primarily found among young children. (5)


==Application to Biotechnology==
==Application to Biotechnology==
Bacteroides thetaiomicron has been found to produce very high levels of a digestive enzyme seen to effective in the breakdown and subsequent digestion of plants, and thus has been a target for improvement of animal digestion. Modification of its activities would be a a good means to increase animal digestion of certain feed materials.
''Bacteroides thetaiotaomicron'' has been used in several studies as a means to illustrate the human-symbiotic relationship, providing insight into how microorganisms interact with the human gut, etc., and thus has been a valuable scientific tool illustrating the coexistence between humans and microbes. (13) These studies have led to some valuable information about ''Bacteroides thetaiotaomicron'' specifically as well.
 
''Bacteroides thetaiotaomicron'' has been found to produce very high levels of a digestive enzyme seen to be effective in the breakdown and subsequent digestion of plants, and thus has been a target for improvement of animal digestion. Modification of its activities would be a a good means to increase animal digestion of certain feed materials.
 
The ability of ''Bacteroides thetaiotaomicron'' to sense its environment and adaptively seek food raises the question of what the specific mechanism is for this process, and through the answers to this question one could maneuver its inherent operations and potentially provide benefits to human hosts through means such as matching diet to nutrient processing capabilities of the microbe. (14) Plant molecular biologists could hypothetically genetically engineer crops with nutritional improvements based upon nutrient processing capabilities of the human gut microbes, such as ''Bacteroides thetaiotaomicron''. (13)


==Current Research==
==Current Research==
1. Functional Genomic and Metabolic Studies of the Adaptations of a Prominent Adult Human Gut Symbiont, Bacteroides thetaiotaomicron, to the Suckling Period: "The adult human gut microbiota is dominated by two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Assembly of this community begins at birth through processes that remain largely undefined. In this report, we examine the adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult distal intestinal microbiota, during the suckling and weaning periods. Germ-free NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was then harvested from the ceca of these hosts during the suckling period (postnatal day 17) and after weaning (postnatal day 30). Whole genome transcriptional profiles were obtained at these two time points using custom B. thetaiotaomicron GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism and gas chromatography-mass spectrometry and biochemical assays of carbohydrate utilization in vivo indicated that in the suckling gut B. thetaiotaomicron prefers host-derived polysaccharides, as well as mono- and oligosaccharides present in mother's milk. After weaning, B. thetaiotaomicron expands its metabolism to exploit abundant, plant-derived dietary polysaccharides. The bacterium's responses to postnatal alterations in its nutrient landscape involve expression of gene clusters encoding environmental sensors, outer membrane proteins involved in binding and import of glycans, and glycoside hydrolases. These expression changes are interpreted in light of a phylogenetic analysis that revealed unique expansions of related polysaccharide utilization loci in three human alimentary tract-associated Bacteroidetes, expansions that likely reflect the evolutionary adaptations of these species to different nutrient niches."
"Functional Genomic and Metabolic Studies of the Adaptations of a Prominent Adult Human Gut Symbiont"  


2. Specificity of a Bacteroides thetaiotaomicron Marker for Human Feces: "A bacterial primer set, known to produce a 542-bp amplicon specific for Bacteroides thetaiotaomicron, generated this product in PCR with 1 ng of extracted DNA from 92% of 25 human fecal samples, 100% of 20 sewage samples, and 16% of 31 dog fecal samples. The marker was not detected in 1 ng of fecal DNA from 61 cows, 35 horses, 44 pigs, 24 chickens, 29 turkeys, and 17 geese."
The adaptations of ''Bacteroides thetaiotaomicron'' during the suckling (postnatal day 17) and weaning periods (postnatal day 30) was explored as germ-free mice were inoculated with the bacterium present from their mothers. The bacterium was harvested from these hosts at the suckling period and weaning period respectively. In the suckling gut ''B. thetaiotaomicron'' feeds on polysaccharides derived from the host, as well as mono- and oligosaccharides, which are present in the mother's milk. After weaning, plant based polysaccharides are metabolized by ''B. thetaiotaomicron.'' Expression of gene clusters which code for environmental sensors, glycoside hydrolases and outer membrane proteins necessary for binding and import of starches all comes as a ''B. thetaiotaomicron's'' postnatal response. (3) 


"Results of the present study indicate that the B. thetaiotaomicron test has the potential to become a valuable addition to the fecal source tracking "toolbox." In this context, the utility and eventual role of this assay will be determined by further evaluation."


3. First Isolation of Bacteroides thetaiotaomicron from a Patient with a Cholesteatoma and Experiencing Meningitis: "A 45-year-old man with a cholesteatoma experienced purulent meningitis. Microbial analysis of cerebrospinal fluid yielded in pure culture a gram-negative bacillus. Phenotypic methods were suggestive of a Bacteroides distasonis or either a Bacteroides thetaiotaomicron or Bacteroides ovatus infection. The isolate was identified by 16S rRNA gene sequence analysis as B. thetaiotaomicron. This is the first case of B. thetaiotaomicron meningitis in pure culture"


"We report on the first case of meningitis due to B. thetaiotaomicron as a unique etiological agent. Isolation has been made possible by the systematic inoculation of the CSF sample in anaerobic media. This isolate was further identified by 16S rRNA gene sequencing, illustrating the usefulness of this method for identification to the species level. This well-defined identification allowed us to describe the natural history and the clinical and biological features of our patient's meningitis and, finally, the antibiotic susceptibility of the etiologic agent, B. thetaiotaomicron."
"Specificity of a Bacteroides thetaiotaomicron Marker for Human Feces" (4)
 
The predominance of ''B. thetaiotaomicron'' in human feces makes it a worthy candidate as a marker of human fecal matter. A bacterial primer set for it was detected in a vast majority of human feces in the study, but in only 16% of dog fecal samples, and in no cow, horse, pig, chicken, turkey, or geese samples. Since the health risk for contact with human feces is generally higher than that with non-human feces, this is an important development in terms of identifying human fecal matter. This new method provides a much quicker and more accurate method than previous ones, as culturing of fecal indicator bacteria is not a necessity nor is the requirement of a host library which can be faulty and/or time consuming. (4)
 
 
 
 
"First Isolation of Bacteroides thetaiotaomicron from a Patient with a Cholesteatoma and Experiencing Meningitis" (5)
 
This is the first case of a pure culture sample of ''B. thetaiotaomicron'' meningitis. The case involved a 45 year old man experiencing purulent meningitis and through microbial analysis of the cerebrospinal fluid was determined to be caused by ''B. thetaiotaomicron.''
 
The man had hearing loss for many years prior, and was admitted to the hospital following profuse ear discharge. Cases of meningitis are not simple to diagnose and the 16S rRNA gene sequence analysis method is credited with allowing the identification of the clinical isolate. It has been found to be 'more reliable than phenotypic methods in accurate species-level identification.' (5)


==References==
==References==


http://www.ebi.ac.uk/integr8/OrganismStatsAction.do?orgProteomeId=127
1.) http://www.ebi.ac.uk/integr8/OrganismStatsAction.do?orgProteomeId=127
 
2.) http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=226186&lvl=3&lin=f&keep=1&srchmode=1&unlock
 
3.) [http://www.jbc.org/cgi/content/full/281/47/36269 Bjursell MK, Martens EC, Gordon JI. "Functional genomic and metabolic studies of the adaptations of a prominent adult human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period." J Biol Chem. 2006 Nov 24;281(47):36269-79. Epub 2006 Sep 12]
 
4.) [http://aem.asm.org/cgi/content/full/71/8/4945?view=long&pmid=16085903 Carson CA, Christiansen JM, Yampara-Iquise H, Benson VW, Baffaut C, Davis JV, Broz RR, Kurtz WB, Rogers WM, Fales WH. "Specificity of a Bacteroides thetaiotaomicron marker for human feces." Appl Environ Microbiol. 2005 Aug;71(8):4945-9.]
 
5.) [http://jcm.asm.org/cgi/content/full/43/3/1467?view=long&pmid=15750136 Feuillet L, Carvajal J, Sudre I, Pelletier J, Thomassin JM, Drancourt M, Cherif AA. "First isolation of Bacteroides thetaiotaomicron from a patient with a cholesteatoma and experiencing meningitis." J Clin Microbiol. 2005 Mar;43(3):1467-9.]
 
6.) [http://jb.asm.org/cgi/reprint/150/3/1008 Salyers, Abigail A., O'brien M., and Kotarski, S.F. "Utilization of Chondroitin Sulfate by Bacteroides thetaiotaomicron Growing in Carbohydrate-Limited Continuous Culture." JOURNAL OF BACTERIOLOGY, June 1982, p. 1008-1015]
 
7.) [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10986238 Shipman, Joseph A., Berleman, J.E.,Salyers, A.A. "Characterization of Four Outer Membrane Proteins Involved in Binding Starch to the Cell Surface of Bacteroides thetaiotaomicron." J Bacteriol. 2000 October; 182(19): 5365–5372.] 
 
8.) [http://www.sciencemag.org/cgi/content/full/299/5615/2074 Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L., Chiang, H.C., Hooper, L.V., and Gordon, J.I. "A genomic view of the human-Bacteroides thetaiotaomicron symbiosis." Science (2003) 299:2074-2076.]
 
9.) [http://jb.asm.org/cgi/content/full/181/23/7206?view=long&pmid=10572122 Shipman, Joseph A., Cho, Hong Kyu, Siegel, H.A., and Salyers, A.A, "Physiological Characterization of SusG, an Outer Membrane Protein Essential for Starch Utilization by Bacteroides thetaiotaomicron." Journal of Bacteriology, December 1999, p. 7206-7211, Vol. 181, No. 23.]


http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=226186&lvl=3&lin=f&keep=1&srchmode=1&unlock
10.) [http://jb.asm.org/cgi/content/full/183/24/7198?view=long&pmid=11717279 Cho, Hong Kyu, Cho, D., Wang G.R., Salyers A.A. "New Regulatory Gene That Contributes to Control of Bacteroides thetaiotaomicron Starch Utilization Genes." Journal of Bacteriology, December 2001, p. 7198-7205, Vol. 183, No. 24.]


[http://jb.asm.org/cgi/reprint/150/3/1008 Salyers, Abigail A., O'brien M., and Kotarski, S.F. "Utilization of Chondroitin Sulfate by Bacteroides thetaiotaomicron Growing in Carbohydrate-Limited Continuous Culture." JOURNAL OF BACTERIOLOGY, June 1982, p. 1008-1015]
11.) [http://jcm.asm.org/cgi/content/full/42/4/1727?view=long&pmid=15071033 Teng, L.-J., P.-R. Hsueh, Y.-H. Huang, and J.-C. Tsai. 2004. "Identification of Bacteroides thetaiotaomicron on the basis of an unexpected specific amplicon of universal 16S ribosomal DNA PCR." Journal of Clinical Microbiology, April 2004, p. 1727-1730, Vol. 42, No. 4.]


[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10986238 Shipman, Joseph A., Berleman, J.E.,Salyers, A.A. "Characterization of Four Outer Membrane Proteins Involved in Binding Starch to the Cell Surface of Bacteroides thetaiotaomicron." J Bacteriol. 2000 October; 182(19): 5365–5372.]  
12.) [http://jb.asm.org/cgi/content/full/182/12/3559?view=long&pmid=10852890 Wang Jun, Shoemaker N.B., Wang G.R., Salyers A.A., "Characterization of a Bacteroides Mobilizable Transposon, NBU2, Which Carries a Functional Lincomycin Resistance Gene." Journal of Bacteriology, June 2000, p. 3559-3571, Vol. 182, No. 12.]


[http://www.sciencemag.org/cgi/content/full/299/5615/2074 Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L., Chiang, H.C., Hooper, L.V., and Gordon, J.I. "A genomic view of the human-Bacteroides thetaiotaomicron symbiosis." Science (2003) 299:2074-2076.]
13.) [http://www.pnas.org/cgi/content/full/100/18/10452 Xu, Jian, and Gordon, J.I. "Honor thy symbionts." PNAS, September 2, 2003, vol. 100, no. 18, 10452-10459.]


14.) [http://www.pnas.org/cgi/content/full/103/23/8834 Sonnenburg, Erica D., Sonnenburg, J.L., Manchester, J.K., Hansen, E.E., Chiang, H.C., And Gordon, J.I. "A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism." PNAS, June 6, 2006, vol. 103, no. 23, 8834-8839] 






Edited by Bashar Mirza, student of [mailto:ralarsen@ucsd.edu Rachel Larsen] and Kit Pogliano
Edited by Bashar Mirza, student of [mailto:ralarsen@ucsd.edu Rachel Larsen] and Kit Pogliano

Latest revision as of 01:03, 6 June 2011

This is a curated page. Report corrections to Microbewiki.

A Microbial Biorealm page on the genus Bacteroides thetaiotaomicron

Classification

Higher order taxa

Bacteria; Bacteroidetes; Bacteroidetes (class); Bacteroidales; Bacteroidaceae (2)

Species

Bacteroides thetaiotaomicron (2)

Description and significance

Bacteroides thetaiotaomicron, a Gram-negative anaerobic microbe, resides in and dominates the human intestinal tract . It consists of a 4776 member proteome containing the structural means to bring in and hydrolyze non-digestible polysaccharides as well as an environment sensing mechanism consisting of outer membrane proteins. Initially isolated from fecal matter, Bacteroides thetaiotaomicron has great importance in terms of the study of the symbiotic bacteria-host relationships within the human intestine as well as for its digestive abilities and potential breakdown of digested plants. (8) Its contributions to postnatal gut development, host physiology, and metabolic capabilities it provides the host, are among the significant benefits it relays. (13) However, it is also a key anaerobic gram-negative bacterial pathogen with extreme disease causing potential as well as antibiotic resistance, which is of clinical interest.

Genome structure

Bacteroides thetaiotaomicron consists of a 6.26 Mb genome containing 4776 protein coding genes. The genome exists as one circular chromosome made of double stranded DNA. The GC content is 42.8% and 90% of the genome is involved in coding for proteins essential in the binding and import of various polysachharides. (1,8)

Additionally, Bacteroides thetaiotaomicron consists of one circular plasmid (p5482) which is 33,038 bp long, containing 38 genes coding for 38 proteins which function mainly in environmental sensing. The GC content of the plasmid is 47.2% and 83% of the genome is involved in coding for proteins. [1] This 33 kb plasmid is one of several types of mobile genetic elements, including 63 transposases and four homologs of the conjugative transposon CTnDOT. The broad range of CTnDOT hosts as well as presence of CTn leads to the theory that microevolution could occur by means of DNA transfer between B. thetaiotaomicron and other forms of bacteria residing in the human gut. (8)

Another interesting feature of B. thetaiotaomicron is that a large portion of its genome is involved in the harvesting and metabolizing of dietary polysaccharides. The co-localization of these genes involved in polysaccharide metabolism along with ECF-type sigma factors (important in sensing envoronmental cues) allow B. thetaiotaomicron to coordinate nutrient availability with expression of these specific genes. (8)

Cell structure and metabolism

Bacteroides thetaiotaomicron is an obligate anaerobe, a major endosymbiont of the human gut. The bacterium uses various polysaccharides as its source of carbon and energy. B. thetaiotaomicron is able to use amylose, amylopectin, and pullulan (all three forms of starch) in addition to maltooligosaccharides. (9) Thus, the organism digests complex plant materials that human enzymes cannot, and it makes an important contribution to human caloric.
A key step in the metabolism of the polysaccharides entails their binding to the cell surface before undergoing hydrolysis. This allows for the efficient sequestration of hydrolysis products. Cell associated enzymes are responsible for hydrolyzing the polysaccharides into small fragments which are easily digestible. This binding and cleavage of the large substrate occurs either before or during translocation into the periplasm. The outer membrane-associated multi-protein complex involved in this digestion process separates substrate binding and hydrolysis using different proteins for each task. (7)

The specific starch utilization system of B. thetaiotaomicron consists of a structure of seven sus (starch utilization genes) structural genes (susA to susG). Most of these genes encode proteins involved in the binding and hydrolysis of starch, and are separated into two transcriptional segments (susA and susB to susG respectively). Maltose as well as higher oligomers of starch are important in regulating structural gene expression, as the sus structural genes are only expressed in their presence. The expression of sus genes is regulated by the regulatory proteins SusR and MalR, which are both always expressed regardless of environmental cues. These two regulons make up for all of the genes needed to grow on starch and maltotriose. (10)

Ecology

Bacteroides thetaiotaomicron is a major component of the adult intestine and has been used as a useful model for the study of human-bacterial symbiosis. Its metabolic function for humans is to degrade plant polysacharides, a very essential capability for the human gut. Additionally, it is very important during the postnatal transition between mother's milk and a diet heavily consisting of plant starches. It has been found to stimulate angiogenesis (growth of new blood vessels from pre-existing vessels) within the gut, due to a microbial signal via bacterial sensing Paneth cells. B. thetaiotaomicron benefits its host by providing sufficient absorptive ability for nutrients the microbe helps process. Another postnatal developmental process within the gut mediated by Bacteroides thetaiotaomicron is the formation of the intestinal mucosal barrier, which helps protect the host against pathogenic invasion via the regulation of the expression of species-specific protein antibiotics. (13)

The environment sensing regulatory apparatus present in B. thetaiotaomicron allows for adaptive food seeking, which stabilizes food webs, and subsequently leads to the longevity of communities. (13) This ability to adaptively 'forage' is an area of biotechnical interest. (14)

Pathology

Bacteroides thetaiotaomicron is the second most common infectious anaerobic gram-negative bacteria. It is considered an opportunistic pathogen, frequently associated with peritonitis, septicemia, and wound infections. B. thetaiotaomicron is capable of causing very serious infections, such as intra-abdominal sepsis and bacteremia. It's resistance to antimicrobial agents is a cause for major concern, and thus methods to identify B. thetaiotaomicron in clinical specimens is of utmost importance. (11)

The many self-transmissable and mobile genetic elements carried by B. thetaiotaomicron are seen as the likely culprits for the spread of antibiotic resistance genes. Antibiotic resistance genes have been found on conjugative transposons ('integrated DNA elements that excise themselves to form a covalently closed circular intermediate') (12), as well as on conjugative and mobilizable plasmids (circular, self-replicating DNA molecule). (12)

Anaerobes in general can cause infection whenever they invade a sterile fluid or tissue environment, such as cerebrospinal fluid. An example of such an event relating to the Bacteroides genus is Bacteroides meningitis, which has been identified in patients with digestive bacterial proliferation making its way to the subarachnoidal space as well as in patients following the spread of ear infections. The Bacteroides genus provides the main agents of anaerobic meningitis, however fewer than 100 cases of Bacteroides meningitis have been reported in English literature, and they are primarily found among young children. (5)

Application to Biotechnology

Bacteroides thetaiotaomicron has been used in several studies as a means to illustrate the human-symbiotic relationship, providing insight into how microorganisms interact with the human gut, etc., and thus has been a valuable scientific tool illustrating the coexistence between humans and microbes. (13) These studies have led to some valuable information about Bacteroides thetaiotaomicron specifically as well.

Bacteroides thetaiotaomicron has been found to produce very high levels of a digestive enzyme seen to be effective in the breakdown and subsequent digestion of plants, and thus has been a target for improvement of animal digestion. Modification of its activities would be a a good means to increase animal digestion of certain feed materials.

The ability of Bacteroides thetaiotaomicron to sense its environment and adaptively seek food raises the question of what the specific mechanism is for this process, and through the answers to this question one could maneuver its inherent operations and potentially provide benefits to human hosts through means such as matching diet to nutrient processing capabilities of the microbe. (14) Plant molecular biologists could hypothetically genetically engineer crops with nutritional improvements based upon nutrient processing capabilities of the human gut microbes, such as Bacteroides thetaiotaomicron. (13)

Current Research

"Functional Genomic and Metabolic Studies of the Adaptations of a Prominent Adult Human Gut Symbiont"

The adaptations of Bacteroides thetaiotaomicron during the suckling (postnatal day 17) and weaning periods (postnatal day 30) was explored as germ-free mice were inoculated with the bacterium present from their mothers. The bacterium was harvested from these hosts at the suckling period and weaning period respectively. In the suckling gut B. thetaiotaomicron feeds on polysaccharides derived from the host, as well as mono- and oligosaccharides, which are present in the mother's milk. After weaning, plant based polysaccharides are metabolized by B. thetaiotaomicron. Expression of gene clusters which code for environmental sensors, glycoside hydrolases and outer membrane proteins necessary for binding and import of starches all comes as a B. thetaiotaomicron's postnatal response. (3)


"Specificity of a Bacteroides thetaiotaomicron Marker for Human Feces" (4)

The predominance of B. thetaiotaomicron in human feces makes it a worthy candidate as a marker of human fecal matter. A bacterial primer set for it was detected in a vast majority of human feces in the study, but in only 16% of dog fecal samples, and in no cow, horse, pig, chicken, turkey, or geese samples. Since the health risk for contact with human feces is generally higher than that with non-human feces, this is an important development in terms of identifying human fecal matter. This new method provides a much quicker and more accurate method than previous ones, as culturing of fecal indicator bacteria is not a necessity nor is the requirement of a host library which can be faulty and/or time consuming. (4)



"First Isolation of Bacteroides thetaiotaomicron from a Patient with a Cholesteatoma and Experiencing Meningitis" (5)

This is the first case of a pure culture sample of B. thetaiotaomicron meningitis. The case involved a 45 year old man experiencing purulent meningitis and through microbial analysis of the cerebrospinal fluid was determined to be caused by B. thetaiotaomicron.

The man had hearing loss for many years prior, and was admitted to the hospital following profuse ear discharge. Cases of meningitis are not simple to diagnose and the 16S rRNA gene sequence analysis method is credited with allowing the identification of the clinical isolate. It has been found to be 'more reliable than phenotypic methods in accurate species-level identification.' (5)

References

1.) http://www.ebi.ac.uk/integr8/OrganismStatsAction.do?orgProteomeId=127

2.) http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=226186&lvl=3&lin=f&keep=1&srchmode=1&unlock

3.) Bjursell MK, Martens EC, Gordon JI. "Functional genomic and metabolic studies of the adaptations of a prominent adult human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period." J Biol Chem. 2006 Nov 24;281(47):36269-79. Epub 2006 Sep 12

4.) Carson CA, Christiansen JM, Yampara-Iquise H, Benson VW, Baffaut C, Davis JV, Broz RR, Kurtz WB, Rogers WM, Fales WH. "Specificity of a Bacteroides thetaiotaomicron marker for human feces." Appl Environ Microbiol. 2005 Aug;71(8):4945-9.

5.) Feuillet L, Carvajal J, Sudre I, Pelletier J, Thomassin JM, Drancourt M, Cherif AA. "First isolation of Bacteroides thetaiotaomicron from a patient with a cholesteatoma and experiencing meningitis." J Clin Microbiol. 2005 Mar;43(3):1467-9.

6.) Salyers, Abigail A., O'brien M., and Kotarski, S.F. "Utilization of Chondroitin Sulfate by Bacteroides thetaiotaomicron Growing in Carbohydrate-Limited Continuous Culture." JOURNAL OF BACTERIOLOGY, June 1982, p. 1008-1015

7.) Shipman, Joseph A., Berleman, J.E.,Salyers, A.A. "Characterization of Four Outer Membrane Proteins Involved in Binding Starch to the Cell Surface of Bacteroides thetaiotaomicron." J Bacteriol. 2000 October; 182(19): 5365–5372.

8.) Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L., Chiang, H.C., Hooper, L.V., and Gordon, J.I. "A genomic view of the human-Bacteroides thetaiotaomicron symbiosis." Science (2003) 299:2074-2076.

9.) Shipman, Joseph A., Cho, Hong Kyu, Siegel, H.A., and Salyers, A.A, "Physiological Characterization of SusG, an Outer Membrane Protein Essential for Starch Utilization by Bacteroides thetaiotaomicron." Journal of Bacteriology, December 1999, p. 7206-7211, Vol. 181, No. 23.

10.) Cho, Hong Kyu, Cho, D., Wang G.R., Salyers A.A. "New Regulatory Gene That Contributes to Control of Bacteroides thetaiotaomicron Starch Utilization Genes." Journal of Bacteriology, December 2001, p. 7198-7205, Vol. 183, No. 24.

11.) Teng, L.-J., P.-R. Hsueh, Y.-H. Huang, and J.-C. Tsai. 2004. "Identification of Bacteroides thetaiotaomicron on the basis of an unexpected specific amplicon of universal 16S ribosomal DNA PCR." Journal of Clinical Microbiology, April 2004, p. 1727-1730, Vol. 42, No. 4.

12.) Wang Jun, Shoemaker N.B., Wang G.R., Salyers A.A., "Characterization of a Bacteroides Mobilizable Transposon, NBU2, Which Carries a Functional Lincomycin Resistance Gene." Journal of Bacteriology, June 2000, p. 3559-3571, Vol. 182, No. 12.

13.) Xu, Jian, and Gordon, J.I. "Honor thy symbionts." PNAS, September 2, 2003, vol. 100, no. 18, 10452-10459.

14.) Sonnenburg, Erica D., Sonnenburg, J.L., Manchester, J.K., Hansen, E.E., Chiang, H.C., And Gordon, J.I. "A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism." PNAS, June 6, 2006, vol. 103, no. 23, 8834-8839


Edited by Bashar Mirza, student of Rachel Larsen and Kit Pogliano