Bacteroides Fragilis
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''Bacteroides fragilis'' is an
anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: *Adhesive#Anaerobic, Anaerobic ad ...
,
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
, pleomorphic to
rod-shaped Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria (and archae ...
bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...
. It is part of the normal microbiota of the human colon and is generally
commensal Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit f ...
, but can cause infection if displaced into the bloodstream or surrounding tissue following surgery, disease, or trauma.


Habitat

''Bacteroides fragilis'' resides in the human gastrointestinal tract and is essential to healthy gastrointestinal function such as mucosal immunity and host nutrition. As a
mesophile A mesophile is an organism that grows best in moderate temperature, neither too hot nor too cold, with an optimum growth range from . The optimum growth temperature for these organisms is 37 °C (about 99 °F). The term is mainly applied ...
, optimal growth occurs at 37 °C and a pH around 7.


Morphology

Cells of ''B. fragilis'' are rod-shaped to pleomorphic with a cell size range of 0.5–1.5 × 1.0–6.0 μm.''B. fragilis'' is a Gram-negative bacterium and does not possess
flagella A flagellum (; : flagella) (Latin for 'whip' or 'scourge') is a hair-like appendage that protrudes from certain plant and animal sperm cells, from fungal spores ( zoospores), and from a wide range of microorganisms to provide motility. Many pr ...
or cilia making it immotile. However, it does utilize peritrichous fimbriae for adhesion to other molecular structures. ''B. fragilis'' also utilizes a complex series of surface proteins, lipopolysaccharide chains, and outer membrane vesicles to help survive the volatile intestinal micro-environment.


Metabolism and mutualism in the gut microbiome

''B. fragilis'' is an aerotolerant, anaerobic chemoorganotroph capable of fermenting a wide variety of glycans available in the human gut microenvironment including glucose, sucrose, and fructose. ''B. fragilis'' can also catabolize a variety of biopolymers, polysaccharides, and glycoproteins into smaller molecules which can then be used and further broken down by other microbes. Fatty acids produced by the fermentation of carbohydrates can serve as a source of energy for the host. Cytochrome ''bd'' oxidase is essential for oxygen consumption in ''B. fragilis'' and can allow other obligate anaerobes to survive in the now oxygen-reduced microenvironment. Animals lacking gut bacteria require 30% more caloric intake to maintain body mass.


Environment-sensing systems

The complex environmental-sensory system allows ''B. fragilis'' to survive and adapt in the ever-changing human gut microbiome. This system is composed of many components and can effectively handle a variety of threats to the bacteria.


Bacteriocins

''B. fragilis'' intestinal isolates secrete high levels of
bacteriocin Bacteriocins are proteinaceous or peptide, peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally ...
proteins and are resistant to other bacteriocins secreted by other closely related isolates. This mechanism is believed to reduce the level of intra-specific competition.


Bile salt resistance

''B. fragilis'' utilizes enzymes such as bile salt hydrolase to resist the degrading effects of
bile salt Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
s. Detergent activity of bile salts can permeabilize bacterial membranes which can eventually lead to membrane collapse and/or cell damage.


Oxidative stress response

Proteins such as catalase, superoxide dismutase, and alkyl hydroperoxide reductase protect the organism from harmful oxygen radicals. This permits growth in the presence of nanomolar concentrations of O2.


Antibiotic resistance

Member of the genus ''Bacteroides'' are characterized with having the highest numbers of
antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
mechanisms accompanied by the highest resistance rates amongst anaerobic bacteria. The high resistance to antibiotics of ''B.fragilis'' is mainly attributed to genetic plasticity. Species of the Bacteroidaceae have displayed increasing resistance to antimicrobial agents such as cefoxitin,
clindamycin Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (mi ...
,
metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
,
carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Si ...
s, and
fluoroquinolones Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...
.


Resistance reservoirs

''Bacteroides'' species accumulate a variety of antibiotic/antimicrobial resistance genes as they reside in the gastrointestinal tract. This allows the genetic transfer of these genes to other ''Bacteroides'' species and possibly other more virulent bacteria leading to an overall increase in multi-drug resistance. This is exacerbated by the tendency of resistance genes to be relatively stable even without the presence of the antibiotic.


Epidemiology and pathogenesis

The ''B. fragilis'' group is the most commonly isolated Bacteroidaceae in
anaerobic infection Anaerobic infections are caused by anaerobic bacteria. Obligately anaerobic bacteria do not grow on solid media in room air (0.04% carbon dioxide and 21% oxygen); facultatively anaerobic bacteria can grow in the presence or absence of air. Micro ...
s, especially those that originate from the gastrointestinal microbiota. ''B. fragilis'' is the most prevalent organism in the ''B. fragilis'' group, accounting for 41% to 78% of the isolates of the group. These organisms are resistant to penicillin by virtue of production of
beta-lactamase Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapene ...
, and by other unknown factors. This group was formerly classified as subspecies of ''B. fragilis'' (i.e. ''B. f.'' ssp. ''fragilis'', ''B. f.'' ssp. ''distasonis'', ''B. f.'' ssp. ''ovatus'', ''B. f.'' ssp. ''thetaiotaomicron'', and ''B. f.'' ssp. ''vulgatus''). They have been reclassified into distinct species on the basis of DNA homology studies. ''B. fragilis'' (formerly known as ''B. f.'' ssp. ''fragilis'') is often recovered from
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
,
pleural fluid The pleural cavity, or pleural space (or sometimes intrapleural space), is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable ...
,
peritoneal fluid Peritoneal fluid is a serous fluid made by the peritoneum in the abdominal cavity which lubricates the surface of tissue that lines the abdominal wall and pelvic cavity. It covers most of the organs in the abdomen. An increased volume of peritone ...
, wounds, and brain
abscess An abscess is a collection of pus that has built up within the tissue of the body, usually caused by bacterial infection. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pre ...
es. Although the ''B. fragilis'' group is the most common species found in clinical specimens, it is the least common ''Bacteroides'' present in fecal microbiota, comprising only 0.5% of the bacteria present in stool. Their pathogenicity partly results from their ability to produce capsular polysaccharide, which is protective against
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
and stimulates abscess formation. ''Bacteroides fragilis'' is involved in 90% of anaerobic
peritoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...
infections. It also causes bacteremia associated with intra-abdominal infections, peritonitis and abscesses following rupture of viscus, and subcutaneous abscesses or
burn A burn is an injury to skin, or other tissues, caused by heat, electricity, chemicals, friction, or ionizing radiation (such as sunburn, caused by ultraviolet radiation). Most burns are due to heat from hot fluids (called scalding), soli ...
s near the anus. Though it is gram negative, it has an altered LPS and does not cause endotoxic shock. Untreated ''B. fragilis'' infections have a 60% mortality rate. Enterotoxigenic ''B. fragilis'' is a significant source of chronic
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
in the context of
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...
disease and has been implicated as a risk factor for
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
. The inflammation caused by ''B. fragilis'' induces spermine oxidase, a
polyamine A polyamine is an organic compound having two or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...
catabolic Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipi ...
enzyme, that may result in production of increased
reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...
and
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
leading to colon tumorigenesis.


Anti-inflammatory effects

''B. fragilis'' polysaccharide A (PSA) has been shown to protect animals from experimental diseases like
colitis Colitis is swelling or inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and ...
,
asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
, or
pulmonary The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. ''B. fragilis'' mutants lacking surface polysaccharides cannot easily colonize the intestine. PSA colonization of ''B. fragilis'' in the gut
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
induces
regulatory T cell The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain immune tolerance, tolerance to self-antigens, and prevent autoimmune disease. Treg  ...
s and suppresses pro-inflammatory
T helper 17 cell T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. Howe ...
s.


See also

* List of oncogenic bacteria * Infectious causes of cancer *
Pathogenic bacteria Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are Probiotic, beneficial but others can cause infectious diseases. The nu ...


References


External links


''Bacteroides'' references
in Baron's ''Medical Microbiology'' (online at the
NCBI The National Center for Biotechnology Information (NCBI) is part of the National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is loca ...
br>bookshelf
.
Type strain of ''Bacteroides fragilis'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q221817 Bacteroidia Gram-negative bacteria Gut flora bacteria Anaerobes Pathogenic bacteria