Originally classified in the 1930s as Group D Streptococci, Enterococci were officially given genus status in 1984 after hybridization studies showed a more distant relationship to Streptococci. Enterococci are gram-positive, spherical bacteria that colonize in groups or chains. They are naturally found as part of the digestive tract flora in many organisms, including humans. They are robust microbes able to tolerate relatively high salt and acid concentrations. They also seem to be able to withstand low levels of detergents, explaining why inadequate cleaning procedures can promote Enterococcus infections. What is now recognized as pathogenic Enterococcus was studied as early as the late 1900s. Currently, Enterococcus infections account for 12% of all nosocomial infections, second only to E. coli. An Enterococcus infection can cause complicated abdominal infections, skin and skin structure infections, urinary tract infections and infections of the blood stream. These infections can be difficult to treat, particularly in cases where the strain involved has developed resistance to several antibiotics. Infection can be life threatening in such instances, especially if the patient is already immunodeficient. There are two species of Enterococci which cause the symptoms described above, E. faecalis, which accounts for the majority of infections (79%), and E. faecium. In a study conducted between 1995 and 1997, data were collected from over 15,000 Enterococcus isolates. Of those, less than 2% of E. faecalis were found to be resistant to ampicillin and vancomycin, whereas 83% of the E. faecium isolates were resistant to ampicillin and 52% were resistant to vancomycin. E. faecium is known to have a resistance to several types of antibiotics including quinolones and aminoglycosides. Resistance to penicillin was first observed in E. faecium in 1983, and in 1988 the first cases of resistance to the "antibiotic of last resort", vancomycin, were detected in Europe. Vancomycin-resistant strains of E. faecium were reported in the US in 1989. Resistance to several antibiotics and tolerance for adverse conditions makes E. faecium a major concern for the medical community, which has dubbed this microbe a "supergerm". http://www.jgi.doe.gov/News/Efacium_overvw.htm Description and significance E. faecium is a human pathogen that causes nosocomial bacteremia, surgical wound infection, endocarditis, and urinary tract infections. Nosocomial infections are those acquired in medical setting during treatment of a prior complaint. The normal habitat includes the gastrointestinal tract of a multitude of animals but it can also be found in the oral cavity and vaginal tract. The microbe can survive for long periods of time in soil, sewage, and inside hospitals on a variety of surfaces. It can grow in temperatures ranging from 10 to 45 degrees Celsius, in basic or acidic environments, and in environments which are isotonic or hypertonic. E. faecium is a Gram-positive, spherical cell that can occur in pairs or chains. The colonies formed are 1-2 mm in length and appear wet. The cells are non-motile. E. faecium can be highly drug resistant and acquires its drug resistance by plasmids and conjugative transposons as well as chromosomal genes that encode resistance. Some strains have become resistant to vancomycin, penicillin, gentamicin, tetracycline, erythromycin and teicoplanin. Spread of the disease occurs between patients in hospitals due to transfer of the pathogen by hands or medical instruments. Also antibiotic use can decrease the number of other intestinal bacteria that are susceptible to the antibiotic and decrease competition for the drug resistant E. faecium. E. faecium was known as Streptococcus faecium until its name changed in 1984 due to a re-categorization. Genome structure The Joint Genome Institute in collaboration with Dr. Barbara Murray sequenced the genome of E. faecium in one day. It has an estimated size of 2.8 Mbp. The genome project is still under construction and has not been fully analyzed. E. faecalis is a close relative of E. faecium and its genome has been sequenced and analyzed. The sequencing of a vacomycin resistant E. faecalis strain, Enterococcus facalis V583, revealed 1 circular chromosome and 3 plasmids. The chromosome consists of 3218031 base pairs and each plasmid, pTEF1, pTEF2, pTEF3, consists of 66320, 57660, and 17963 base pairs respectively. Two of the plasmids are pheromone-sensing conjugative plasmids. Also found was a mobile conjugative transposon that encodes vacomycin resistance. Over a quarter of E. feacalis’ 3337 open reading frames are mobile and/or exogenously acquired DNA. These mobile and/or exogenously acquired DNA include seven integrated phage regions, 38 insertion elements, conjugative and composite transposons, a patheogenicity island, and integrated plasma genes. Its ability to acquire outside DNA contributes to E. faecalis’ multiple drug resistance. The genes encoding vacomycin resistance in E. faecalis’ are similar to E. faecalis’ vanB vancomycin-resistance conjugative transposon Tn1549 and were probably transferred as a cassette by lateral gene transfer. Cell structure and metabolism Cell Structure E. faecium is a gram-positive bacterium. Gram-positive cells have a thick peptidogycan layer along with teichoic and lipoteichoic acids. It has circular DNA as well as several plasmids. It is capable of conjugation through the release of sex pheromones and secretes aggregation substances and also forms bioflims. The cell has pili and flagella. Metabolism E. faecium lacks the Krebs’s cycle and respiratory chain and therefore it gains energy through fermentation. It is a facultative anaerobe which means it can make ATP by aerobic respiration if oxygen is present but will utilize fermentation if no oxygen is present. Ecology E. faecium can acquire drug resistance through three types of conjugation: pheromone-responsive plasmids, broad host-range plasmids, and conjugative transposons. Pheromone response plasmid occurs when the cell secretes a sex pheromone for a specific plasmid. When a donor cell comes into contact with the pheromone, transcription of the relevant portion of the plasmid is turned on and it also secretes a sticky substance. The sticky or aggregation substance facilitates the transfer of the plasmid to the recipient cell by helping them to stick together. Transfer of other plasmids can also occur between different genera of bacteria including staphylococci, and streptococci. The consequence of the ability of E. faecium to acquire broad host-range plasmids is that drug resistance can be widely and more easily spread. Conjugative transposons can also transfer antibiotic resistance between genera as well as between gram-positive and gram-negative bacteria because they do not need to cooperate with host machinery in order to insert themselves into a plasmid or chromosome of the bacterium. E. faecium can interact with other bacteria to spread drug resistance through conjugation. Pathology E. faecium is considered a super-bug. It can colonize many organs of the body including the gastrointestinal tract and the skin, and can also survive for long periods on inanimate objects. This along with its multi-drug resistant characteristics makes it a particularly nasty pathogen. Contributing to the virulence of E. faecium is the enterococcal surface protein (Esp). This protein allows the bacteria to aggregate and form bioflims. Strains with the Esp gene are normally found in clinical isolates and not found in strains that colonize the gut. Bioflim formation allows colonization of tubing used in hospitals and can lead to infections of the blood as well as urinary tract infections. Esp gene expression increased under increased temperature as well as a change to anaerobic condition. The regulation of the Esp gene in this way allows E. faecium to change its response when it enters a host. Additional virulence factors include aggregation substance (AS), cytosolin, and gelantinase. AS allows the microbe to bind to target cells and it facilitates the transfer of genetic material between cells. Cytosolin is a protein found in the cytosol and lyses erythrocytes. GeIE can hydrolyze peptides. The presence of virulence factors differ among strains and usually are specific for the host the strain colonizes. Application to Biotechnology E. faecium produces antibacterial peptides called bacteriocins. This microbe can be used in fermenting foods such as cheese and vegetables. It is introduced to the starting cultures to inhibit growth of unwanted microbes. E. faecium can also be used as a probiotic to out-compete deleterious bacteria in the gastrointestinal tract. Current Research A study showed that the metabolism of E. faecium can cause eukaryotic cell DNA damage through its metabolism. Through the autoxidation of membrane bound demethylmenaquinone E. faecium produces superoxide, hydrogen peroxide, and hydroxyl radicals. These oxidants can produce chromosomal instability that can cause polyps and colon cancer. Hydrogen peroxide derived from E. faecium was shown to damage luminal cells in the colon of rats, demonstrating E. faecium’s potential carcinogenic property. As vacomycin resistance increases in E. faecium, health care providers must find novel strategies for treating patients affected by the microbe. Often doctors must venture into uncharted territories to save a patient. In one example a premature infant in a neonatal unit was diagnosed with a vacomycin resistant strain that had infected her central nervous system through a ventriculoperitoneal (VP) shunt. Through laboratory testing it was found that the germ was susceptible to linezolid. As published data of treatment of central nervous system infections with linezolid in infants was unavailable the hospital dosed the infant using the resources at hand. As E. faecium continues to acquire drug resistance novel strategies are needed to combat it. The use of antibiotics in animal feed has caused an increase in resistance to antibiotics. The van A gene began presenting itself outside of hospitals as a result of selective pressure due to antibiotic use. The van A gene was spread through conjugation. Studies have shown that the use of virginiamycin in stock animals produced drug resistant enterococci. http://microbewiki.kenyon.edu/index.php/Enterococcus_faecium |
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