Bacteroides fragilis

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A Microbial Biorealm page on the genus Bacteroides fragilis

Image copyright Dennis Kunkel Microscopy, Inc. of Bacteroides sp.


Classification

Higher order taxa

Superkingdom: Bacteria; Superphylum: Bacteroidetes/Chlorobi group; Phylum: Bacteroidetes; Class: Bacteroidetes; Order: Bacteroidales; Family: Bacteroidaceae; Genus: Bacteroides.

[Use NCBI link]

Species

Bacteroides acidifaciens, Bacteroides barnesiae, Bacteroides caccae, Bacteroides capillosus, Bacteroides cellulosolvens, Bacteroides coagulans, Bacteroides coprocola, Bacteroides denticanum, Bacteroides dorei, Bacteroides eggerthii, Bacteroides finegoldii, Bacteroides fragilis, Bacteroides galacturonicus, Bacteroides gallinarum, Bacteroides helcogenes, Bacteroides intestinalis, Bacteroides massiliensis, Bacteroides nordii, Bacteroides ovatus, Bacteroides pectinophilus, Bacteroides plebeius, Bacteroides pyogenes, Bacteroides salanitronis, Bacteroides salyersiae, Bacteroides splanchnicus, Bacteroides stercoris, Bacteroides suis, Bacteroides tectus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bacteroides xylanolyticus.

NCBI: Taxonomy

Description and significance

Bacteroides fragilis is a gram-negative, rod shape anaerobes, non-motile, and non-sporulating. Many of Bacteroides species live in the colon and intestines of humans and animals [16]. Bacteroides fragilis is found predominantly in the colon and intestinal tract along with E. coli and other species present. Bacteroides fragilis is composed of 30-50% of normal fecal matter in human [4]. Its size is smaller than that of E. coli and they have large vacuoles, which resembles spores but they themselves are non-sporulating organism. They also have enormous capsule with NO cell membrane endotoxin, which limit their pathogenicity [16]. However, they have sphingolipids within their membrane and its peptidoglycan layer contains meso-diaminopimelic acid [16].

Although Bacteroides fragilis makes up from 1-2% of the normal flora in our body [4], they are responsible for 80% of anaerobic infections [16]. As an anaerobic pathogen, Bacteroides fragilis also competes with other organisms inside the colon/intestinal lumen for nutrients and food [16]. This can be of great benefit to our body because when organisms compete, it decreases the availability of nutrients for other dangerous pathogens to grow, harming our body [16].

Most of the Bacteroides fragilis was isolated from human stools, and depending on where the infection is located at, different ways of sampling are available. And utilizing PCR, different assays technique and blotting techniques are also important to aid in the identification of individual components within the sample obtained [14]. Bacteroides fragilis also grow well on blood agar plate, which can be used to identify which antibiotics is best at killing the infected organism [16]: This can be done by growing Bacteroides fragilis in a medium that contains the antibiotics and comparing the growth with respect to different antibiotics.

It is highly important to study Bacteroides fragilis because it is well known to have caused many intestinal infections and it’s highly associated with abscess formation [16]. Abscess formation results in the formation of a fibrous membrane surrounding the infected site caused by Bacteroides fragilis. If left untreated, it will cause major harm to humans and animals. Studies have identified an enterotoxin that is associated with Bacteroides fragilis and it’s the main caused of diarrhea in children and many types of inflammatory diseases in adults [16]. But most importantly, studying Bacteroides fragilis will enable scientists to develop antibiotics to cure the infections cause by the organism.

Genome structure

There are many Bacteroides species that have been sequenced. Bacteroides fragilis have five sequenced genome known thus far plasmid pBI143, NCTC 9343 plasmid pBF9343, NCTC 9343, YCH46, and YCH46 plasmid pBFY46 [10]. Many of the genome sequence are circular DNA with varying lengths. The length ranges from 2747 nucleotides to 5.3 million nucleotides long. The % GC contents ranges from 33 to 43 % [10]. Out of the five sequenced genome, there are three plasmids. Plasmid sequences are usually smaller in length and its % GC contents also vary. The sequence genome of Bacteroides fragilis contains many important genes and proteins that are necessary for survival. They help break down food products and supply nutrients that our body can’t make [4]. And plasmids also contain genes and are used as a way for organisms to transfer genes to its neighboring groups, which helps diversify the organism further [6]. This plays an important role in antibacterial resistance.

NOTE: The Sanger Institute - Allows people to see the circular chromosomal DNA sequence in larger view and details [10].

Cell structure and metabolism

As mentioned before, Bacteroides fragilis is a known pathogen and it is very useful as long as it stays inside the colon/intestinal lumen. Its lifestyles is very diverse; it can utilized simple sugars and involved in many complex pathways necessarily for generation of energy, such as biosynthesis of carbohydrates, lipids, fatty acids and much more. It’s also involved in the generation of metabolites and energy through Glycolysis, Pentose Phosphate Pathway, TCA, and much more [1]. Bacteroides fragilis can only utilized simple sugars because most sugars are absorbed into the small intestine, not much gets pass through the upper gastrointestinal tract for Bacteroides fragilis to use [4]. This therefore, limits the complexity of the organism.

Bacteroides fragilis are also involved in many important metabolic activities in the human flora of the colon. Bacteroides fragilis also produce by-products, including acetic acid, iso-valeric acid and succinic acid [3]; that are then used to generate energy through different pathways. For example, succinic acid is used as the intermediate for the TCA cycle [7]. Carbohydrate fermentation is another mechanism in which Bacteriodes fragilis utilizes some by-products made and other fatty acids as a source for the production of energy [4]. The Bacteroides species also help degrade and deaminated proteins to ammonia, CO2, fatty acids and others that the body utilizes. The Bacteroides species then use the ammonia as nitrogen source but how the Bacteroides species uses nitrogen is still unclear [4].

Ecology

Bacteriodes fragilis lives primarily in humans and animals intestinal/colon flora. As long as Bacteriodes fragilis is retains within the intestinal lumen, its contribution to our body is very diverse. And once Bacteroides fragilis leaves the lumen and travels to adjacent areas and organs, it can be detrimental as it contributed to a variety of infections in the upper body, abdomen, skin and many others [3]. Bacteroides fragilis now act as a pathogen and invades its host by producing the enterotoxins. Due to its role as a pathogen, Bacteroides fragilis can be very complex; they will be able to survive and adapt in most environments like its neighbor, E.coli.

Pathology

Bacteroides fragilis has been studied extensively and it is known to have been the cause of many intestinal inflammations and it’s also the main cause of acute and chronic diarrheal diseases in humans and animals [11]. Bacteroides fragilis is also the cause of abscess formation [16]. Due to the growth at the infection site, abscess formation needs to be cleared as soon as possible otherwise mortality rate can increase. The Bacteroides fragilis that was extracted contains enterotoxins, a factor that is highly associated with diarrheal diseases [14]. The enterotoxins were identified through a conducted study in which samples from patients stool was collected and techniques such as: PCR, assays, different blotting techniques, etc... were used to identify the enterotoxins [14]. Treatment of diarrheal diseases in children is relatively easy, the use of re-hydration to lessen the impact of the disease [11]. As for adults, antibiotics are used.

Bacteroides fragilis is also a predominant anaerobe that was recovered from patients who suffered from meningitis. Symptoms of meningitis differ between infants and adults: In infants, their symptoms include but not limited to fetal distress, rupture of membranes, infected ventriculoperitoneal or ventriculoatrial shunt, and others. Symptoms in adults includes middle ear infection, pulmonary infections, pharyngitis, etc… Most of the cases identified can be treated with antimicrobials that are effective against anaerobes that penetrate the Blood Brain Barrier (ex. Metronidazole, Chloramphenicol) [2].

Some species of Bacteroides produce succinic acid as a virulence factor (ex. Bacteroides fragilis) [7]. Bacteroides fragilis produce polysaccharide capsule high in succinic acid. Once Bacteroides fragilis is released from the capsule, it paralyses the migration of leukocytes, which is required for the site of healing [7]. When the Bacteroides fragilis kills off the leukocytes, the infections grew and if left untreated then the death rate is as high 60% [16]. Succinic acid was used to test the neutrophil function and they have found that the succinic acid enhances the virulence factor of Bacteroides. Another thing they’ve found is that the virulence factor increases with lower pH and in microenvironment with high infections [12].

There are millions of bacteria living in our colon/intestinal lumen and Bacteroides fragilis only makes up a small percentage. Other species includes: E. coli, other Bacteroides species, Shigella, Salmonella, and much more. Bacteroides fragilis also synergize with other bacteria, like E. coli. Due to its proximity to E. coli, Bacteroides fragilis have found a way to transfer plasmid from one organism to another. A plasmid pDP1 have been studied and shown to mediate gene transfer between E. coli and Bacteroides fragilis [6]. The transferring of plasmid is one of many ways in which Bacteroides fragilis developed resistance against many antibiotics. And comparison between the organisms showed that the antibiotic resistance genes are expressed differently amongst aerobic and anaerobic bacteria [6].

The best treatment of Bacteroides fragilis infections is antibiotics. Early treatment and using the right antibiotics is key to curing the infections. For example, 90-100% of Bacteroides fragilis is resistant to ampicillin, and are known to be resistant to penicillin [8]. Many antibiotics out in the market (Chloramphenicol, Metronidazole, Carbapenems), beta-lactam and beta-lactamase inhibitor are all useful against Bacteroides fragilis but due to its complexity, many more studies are being performed to find a yet better antibiotics against this organism to help treat infections [16].

Application to Biotechnology

Through the EBI website, four enzymes were found for Bacteroides fragilis Fragilysin, Phosphonopyruvate decarboxylase, 7-alpha-hydroxysteroid dehydrogenase, and Choloylglycine hydrolase [5]. These enzymes play a role in catalyzing reactions that occur in the biosynthetic pathway. Some also required a cofactor (Magnesium, Zinc) and others utilized (ex. NAD+, NADP+). For example, Fragilysin requires Zinc, which disrupts the tight junctions of the intestinal wall. This is thought to be the enzyme that helps Bacteroides fragilis escape to other parts of the body where it releases its toxin to infect the site of actions [5]. However, this organism does not contribute to any biotechnology known but investigation is still under study.

Current Research

Current research of Bacteroides fragilis includes: development of antibiotics, its infections on fetus and mother, the developmental research of friendly commercial products using by-products of Bacteroides fragilis and much much more.

Because of the unique characteristics of gram-negative bacteria and its resistance to antibiotics, many studies have been done to try and understand its mechanisms of action. Bacteroides fragilis is very unique in a sense that it has its own way of becoming resistant to antibiotics and so far, no studies have been able to identify their mechanisms of action [4]. A new antibiotic under study, Trospectomycin, is used in treatment against Bacteroides fragilis and results suggested that it’s a very good antibiotic against Bacteroides fragilis [8]. In the study, 6 other antimicrobials were used to compare the effects relative to Trospectomycin. Results suggested that Trospectomycin outperformed antibiotics like ampicillin, doxycycline, etc… Trospectomycin is a new parenteral amino-cyclitol, it acts by binding to the 30s subunit and inhibits protein synthesis [8]. It’s proven excellent against many gram-negative bacteria. Still, more research are being performed to understand and to develop antibiotics that will treat infections from all the enterotoxigenic Bacteroides fragilis.

Another case that has been studied is the relationship between Bacteroides fragilis and its pathogenesis on the human genital tract. Although Bacteroides fragilis was isolated, it might not be the sole cause of the genital infections. A study has been done to see the link between Bacteroides fragilis and vaginal infection amongst pregnant women. Although both enterotoxigenic and the non-enterotoxigenic strains of Bacteroides fragilis were found when they did the study, the transmission mechanism is still largely unknown and its role have not been fully understood [9]. Another significant theory being determined is the link between the development of the fetus and the Bacteroides fragilis. They wanted to see whether Bacteroides fragilis might have contributed to any birth defects in newborn such as low birth weights or it’s some other unknown factors [9].

Succinic acid is a by-product produced from Bacteroides species from the end product of their energy metabolism [7]. Succinic acid is important in many commercial products due to its industrial applications in food, pharmaceuticals, cosmetics and many others. Thus far, many succinic acids have been created chemically and have raised major environmental concerns amongst people. A new method is to produce succinic acid by microbial fermentation; it’s simple and environmental friendly [7]. However, its development is still under study.

References

1. Bio/Cyc Database Collection

2. Brook, I. "Meningitis and shunt infection caused by anaerobic bacteria in children." Pediatric Neurology 26.2 (2002):99-105.

3. Dennis Kunkel Microscopy, Inc.

4. ECU (East Carolina University)

5. EMBL-EBI (The European Molecular Biology Laboratory-the European Bioinformatics Institute)

6. GUINEY, DG. "PLASMID TRANSFER FROM ESCHERICHIA-COLI TO BACTEROIDES-FRAGILIS - DIFFERENTIAL EXPRESSION OF ANTIBIOTIC-RESISTANCE PHENOTYPES." Proceedings of the National Academy of Sciences of the United States of America 81.22 (1984):7203-7206.

7. Isar, J, andISAR. "Suceinic acid production from Bacteroides fragilis: Process optimization and scale up in a bioreactor." Anaerobe 12.5-6 (2006):231-237.

8. JACOBUS, NV. "ACTIVITY OF TROSPECTOMYCIN AGAINST BACTEROIDES-FRAGILIS AND OTHER BACTEROIDES SPECIES." Antimicrobial agents and chemotherapy 32.4 (1988):584-586.

9. Leszczynski, P. "Vaginal carriage of enterotoxigenic Bacteroides fragilis in pregnant women." Journal of clinical microbiology 35.11 (1997):2899-2903.

10. NCBI (National Center for Biotechnology Information)

11. Pathela, P. “Enterotoxigenic Bacteroides fragilis-Associated Diarrhea in Children 0-2 Years of Age in Rural Bangladesh.” The Journal of Infectious Diseases 191 (2005):1245-1252.

12. ROTSTEIN, OD. "SUCCINIC ACID, A METABOLIC BY-PRODUCT OF BACTEROIDES SPECIES, INHIBITS POLYMORPHONUCLEAR LEUKOCYTE FUNCTION." Infection and immunity 48.2 (1985):402-408.

13. SANJOAQUIN, VH. "ASSOCIATION OF BACTEROIDES-FRAGILIS WITH CHILDHOOD DIARRHEA." Scandinavian journal of infectious diseases 27.3 (1995):211-215.

14. Shetab, R. "Detection of Bacteroides fragilis enterotoxin gene by PCR." Journal of clinical microbiology 36.6 (1998):1729-1732.

15. The Sanger Institute: Bacteroides Fragilis

16. The World Wide Anaesthestist: Bacteroides fragilis


Edited by Thu-Van Le, student of Rachel Larsen

Source text
16S rRNA accession # [[]]
Family Bacteria [[]]
Genus Bacteroides On the basis of biochemical and chemical criteria there is now good evidence that the genus should be restricted to the type species, Bacteroides fragilis, and closely related orga- nisms (5).
Species Bacteroides fragilis These species exhibit a variety of cellular morphologies and are biochemically and physiologically extremely heterogeneous (2, 16, 19, 26).
Strain [[]]

Genetic characteristics

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 %G+C: size=25 [[{{{Percent G plus C source text}}}]]
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Morphological features

Cell shape bacillus Thus, there is an urgent need to tighten the circumscription of the genus Bacteroides to prevent its continuing use as a repository for a varied collection of obligately anaerobic, gram-negative, nonsporing, rod- shaped bacteria.
Pigments [[]]
Cell wall Cell wall peptidoglycan contains meso-diaminopimelicacid as the diamino acid.
Motility non motile Gram-negative, obligately anaerobic, non- sporeforming, nonmotile, rod-shaped cells.
Biofilm formation [[]]

Environmental parameters

Habitat isolated from [[]]
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Host microbe interactions

Host [[]]
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Metabolism (energy & carbon source)
Mono & di-saccharides [[]]
Polysaccharides [[]]
Amino acids Cell wall peptidoglycan contains meso-diaminopimelicacid as the diamino acid.
Alcohols [[]]
Fatty acids B. fragilis and related species also possess sphingolipids, predominantly methyl branched long-chain fatty acids, and menaquinones as the sole respiratory quinones (5, 22).
Other energy or carbon sources [[]]

Metabolite products

Fermentation products [[]]
Polyalkanoates (plastics) [[]]
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Antibiotic characteristics

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Peer review ready: No Peer review complete: No

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