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Listeria monocytogenes

الكلية كلية الطب     القسم  الاحياء المجهرية     المرحلة 3
أستاذ المادة حبيب صاحب نهر المزيداوي       4/17/2011 12:13:34 PM

Listeria monocytogenes and Listeriosis: 
Listeria monocytogenes is a Gram-positive rod-shaped bacterium. It is the agent of listeriosis, a serious infection caused by eating food contaminated with the bacteria.  Listeriosis has been recognized as an important public health problem in the United States. The disease affects primarily pregnant women, newborns, and adults with weakened immune systems.
Listeriosis is a serious disease for humans; the overt form of the disease has a mortality greater than 25 percent. The two main clinical manifestations are sepsis and meningitis. Meningitis is often complicated by encephalitis, a pathology that is unusual for bacterial infections.
Microscopically, Listeria species appear as small, Gram-positive rods, which are sometimes arranged in short chains. In direct smears they may be coccoid, so they can be mistaken for streptococci. Longer cells may resemble corynebacteria.   Flagella are produced at room temperature but not at 37°C. Hemolytic activity on blood agar has been used as a marker to distinguish Listeria monocytogenes among other Listeria species, but it is not an absolutely definitive criterion. Further biochemical characterization may be necessary to distinguish between the different Listeria species.


Natural Habitats of Listeria and Incidence of Disease
Until about 1960, Listeria monocytogenes was thought to be associated almost exclusively with infections in animals, and less frequently in humans. However, in subsequent years, listeriae, including the pathogenic species L. monocytogenes and L. ivanovii, began to be isolated from a variety of sources, and they are now recognized to be widely distributed in Nature. In addition to humans, at least 42 species of wild and domestic mammals and 17 avian  species, including domestic and game fowl, can harbor listeriae. Listeria monocytogenes is reportedly carried in the intestinal tract of 5-10% of the human population without any apparent symptoms of disease. Listeriae have also been isolated from crustaceans, fish, oysters, ticks, and flies.
The term listeriosis encompasses a wide variety of disease symptoms that are similar in animals and humans.  Listeria monocytogenes causes listeriosis in animals and humans; L. ivanovii causes the disease in animals only, mainly sheep. Encephalitis is the most common form of the disease in ruminant animals. In young animals, visceral or septicemic infections often occur. Intra-uterine infection of the fetus via the placenta frequently results in abortion in sheep and cattle.
The true incidence of listeriosis in humans is not known, because in the average healthy adult, infections are usually asymptomatic, or at most produce a mild influenza-like disease. Clinical features range from mild influenza-like symptoms to meningitis and/or meningoencephalitis. Illness is most likely to occur in pregnant women, neonates, the elderly and immunocompromised individuals, but apparently healthy individuals may also be affected. In the serious (overt) form of the disease, meningitis, frequently accompanied by septicemia, is the most commonly encountered disease manifestation. In pregnant women, however, even though the most usual symptom is a mild influenza-like illness without meningitis, infection of the fetus is extremely common and can lead to abortion, stillbirth, or delivery of an acutely ill infant.
In humans, overt listeriosis following infection with L. monocytogenes is usually sporadic, but outbreaks of epidemic proportions have occurred. The source of the bacteria was a certain brand of "pasteurized" soft cheese that apparently had gotten contaminated with non pasteurized (raw) milk during the manufacturing process.
In 2002, a multistate outbreak of Listeria monocytogenes infections with 46 culture-confirmed cases, seven deaths, and three stillbirths or miscarriages in eight states was linked to eating sliced turkey deli meat. One intact food product and 25 environmental samples from a poultry processing plant yielded L. monocytogenes. Two environmental isolates from floor drains were indistinguishable from that of outbreak patient isolates, suggesting that the plant might be the source of the outbreak.


Pathogenesis
Listeria monocytogenes is presumably ingested with raw, contaminated food. An invasin secreted by the pathogenic bacteria enables the listeriae to penetrate host cells of the epithelial lining. The bacterium is widely distributed so this event may occur frequently. Normally, the immune system eliminates the infection before it spreads. Adults with no history of listeriosis have T lymphocytes primed specifically by Listeria antigens. However, if the immune system is compromised, systemic disease may develop. Listeria monocytogenes multiplies not only extracellularly but also intracellularly, within macrophages after phagocytosis, or within parenchymal cells which are entered by induced phagocytosis.
In mice infected with L. monocytogenes, the bacteria first appear in macrophages and then spread to hepatocytes in the liver. The bacteria stimulate a CMI response that includes the production of TNF, gamma interferon, macrophage activating factors and  a cytotoxic T cell response. Possibly, in humans, a failure to control L. monocytogenes by means of CMI allows the bacteria to spread systemically. As well, unlike other bacterial pathogens, Listeria are able to penetrate the endothelial layer of the placenta and thereby infect the fetus.


Virulence Factors
Growth at low temperatures:
A peculiar property of L. monocytogenes that affects its food-borne transmission is the ability to multiply at low temperatures. The bacteria may therefore grow and accumulate in contaminated food stored in the refrigerator. So it is not surprising that listeriosis is usually associated with ingestion of milk, meat or vegetable products that have been held at refrigeration temperatures for a long period of time.


Motility:
As in the case of Vibrio cholerae, wherein movement, attachment and penetration of the intestinal mucosa are determinants of infection (if not disease), this was thought to be the situation with Listeria, which is also acquired by ingestion and must also find a way to attach to the intestinal mucosa. With cholera, the actively-motile vibrios are thought to use their flagella to swim against the peristaltic movement of the bowel content and to penetrate (by swimming laterally) the mucosal lining of the gut where they adhere. Curiously, although Listeria are actively motile by means of peritrichous flagella at room temperature (20-25°C), the organisms do not synthesize flagella at body temperatures (37°C). Instead, virulence is associated with another type of motility: the ability of the bacteria to move themselves into, within and between host cells by polymerization of host cell actin at one end of the bacterium ("growing actin tails") that can propel the bacteria through cytoplasm. However, one should not totally dismiss the advantage of flagellar motility for existence and spread of the bacteria outside of the immediate host environment.


Adherence and invasion:
Listeria can attach to and enter mammalian cells. The bacterium is thought to attach to epithelial cells of the GI tract by means of D-galactose residues on the bacterial surface which adhere to D-galactose receptors on the host cells. If this is correct, it is the opposite of the way that most other bacterial pathogens are known to adhere, i.e., the bacterium displays the protein or carbohydrate ligand on its surface and the host displays the amino acid or sugar residue to which the ligand binds. Having said this, macrophages are well known to have "mannose binding receptors" on their surface whose function presumably is to ligand to bacterial surface polysaccharides that terminate in mannose, as a prelude to phagocytic uptake. The bacteria are then taken up by induced phagocytosis, analogous to the situation in Shigella. An 80 kDa membrane protein called internalin probably mediates invasion. A complement receptor on macrophages has been shown to be the internalin receptor, as well.
After engulfment, the bacterium may escape from the phagosome before phagolysosome fusion occurs mediated by a toxin, which also acts as a hemolysin, listeriolysin O (LLO). This toxin is one of the so-called SH-activated hemolysins, which are produced by a number of other Gram-positive bacteria, such as group A streptococci (streptolysin O), pneumococci (pneumolysin), and Clostridium perfringens. The hemolysin gene is located on the chromosome within a cluster of other virulence genes that are all regulated by a common promoter. Survival of the bacterium within the phagolysosome also occurs, aided by the bacterium s ability to produce catalase and superoxide dismutase which neutralize the effects of the phagocytic oxidative burst.
Additional genetic determinants are necessary for further steps in the intracellular life cycle of L. monocytogenes. One particular gene product, Act A (encoded by actA) promotes the polymerization of actin, a component of the host cell cytoskeleton, on the bacterial surface. Within the host cell environment, surrounded by a sheet of actin filaments, the bacteria reside and multiply. The growing actin sheet functions as a propulsive force which drives the bacteria across the intracellular pathways until they finally reach the surface. Then, the host cell is induced to form slim, long protrusions containing living L. monocytogenes. Those cellular projections are engulfed by adjacent cells, including non-professional phagocytes such as parenchymal cells. By such a mechanism, direct cell-to-cell spread of Listeria in an infected tissue may occur without an extracellular stage.


Host Defenses:
Because L. monocytogenes multiplies intracellularly, it is largely protected against circulating immune factors (AMI) such as antibodies and complement-mediated lysis. The effective host response is cell-mediated immunity (CMI), involving both lymphokines (especially interferon) produced by CD4+ (TH1) cells and direct lysis of infected cells by CD8+ (Tc) cells. Both of these defense mechanisms are expressed in the microenvironment of the infected foci, which are organized as granulomas, characterized by a central accumulation of macrophages with irregularly shaped nuclei, and by peripheral lymphocytes recognizable by rounded nuclei and a narrow border of intensely staining cytoplasm.


Treatment and Prevention:
If diagnosed early enough, antibiotic treatment of pregnant women or immunocompromised individuals can prevent serious consequences of the disease. Antibiotics effective against Listeria species include ampicillin, vancomycin, ciprofloxacin, linezolid and azithromycin. However, early diagnosis is the exception rather than the rule, since the first signs of a case or an outbreak are reports of stillbirth or serious infections resembling listeriosis. By then, any cohorts who have become infected from eating the same food are likely recovered from an inapparent or flu-type infection, or they themselves may have developed serious disease. However, processed foods known to be the source of Listeria that may still be in the market place, restaurant or home should obviously not be used, and recalls should be imperative. It must also be constantly recognized that L. monocytogenes is able to grow at low temperatures.



 Summary: About 2500 cases of listeriosis occur each year in the United States. The initial symptoms are often fever, muscle aches, and sometimes gastrointestinal symptoms such as nausea or diarrhea. The illness may be mild and ill persons sometimes describe their illness as flu-like. If infection spreads to the nervous system, symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions can occur. Most cases of listeriosis and most deaths occur in adults with weakened immune systems, the elderly, pregnant women, and newborns. However, infections can occur occasionally in otherwise healthy persons. Infections during pregnancy can lead to miscarriages, stillbirths, and infection of newborn infants. Outbreaks of listeriosis have been linked to a variety of foods especially processed meats (such as hot dogs, deli meats, and paté) and dairy products made from unpasteurized milk.


 


المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .