Listeria monocytogenes

by Jamie Puglisi 


Introduction

Listeria monocytogenes, a motile, gram-positive rod, is an opportunistic food-borne pathogen capable of causing listeriosis in humans. Listeriosis includes manifestations of septicemia, meningitis, pneumonia, and encephalitis. L. monocytogenes is also implicated in miscarriages, stillbirth, and premature birth for pregnant women. L. monocytogenesis a tough bacterium resistant to freezing, drying, and heat; most strains have been shown to be pathogenic. It is hypothesized that 1-10% of humans are intestinal carriers of L. monocytogenes. Over 37 mammalian species, including wild and domestic animals, are capable of L. monocytogenes infection and transmission. Extensive environmental reservoirs for L. monocytogenes include soil, water, vegetation, sewage, silage, and the intestinal tract of various animals.

Encounter

L. monocytogenes is transmitted by ingestion of contaminated food or water. The bacterium is associated with raw milk, cheeses, (particularly soft varieties) ice cream, raw vegetables, fermented raw-meat sausages, raw and cooked poultry, raw meats, and raw and smoked fish. It is capable of growing at temperatures as low as 3°C allowing multiplication in refrigerated foods, making L. monocytogenes infection particularly hard to avoid. The infective dose has not been determined, but is believed to vary with the susceptibility of the individual. It may be less than 1000 bacterium in the immuno-compromised individual.


Entry, Multiplication, and Spread

L. monocytogenes initially gains access to the body through the gastrointestinal tract but is capable of infecting the blood through monocytes, macrophages and polymorphonuclear leukocytes. The bacterium is also capable of infecting hepatocytes, endothelial cells, and epithelial cells. L. monocytogenes lives as an intracellular pathogen inside these host cells, using the cell’s own machinery to survive. Pathogenic L. monocytogenes go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. The bacterium is first phagocytosed by these cells and secretes a pore-forming toxin called listeriolysin, which allows the bacterium to escape from the phagosome. All virulent strains of L. monocytogenes synthesize and secrete listeriolysin. Phospholipase A and B are other virulence factors that facilitate escape of L. monocytogenes from the phagosome. Once out of the phagosome L. monocytogenes is capable of rapid division in the cytoplasm, evading the immune response and moving throughout the cytoplasm from cell to cell. L. monocytogenes is well known for its ability to propel itself like a rocket through the cell cytoplasm. This is the result of the bacterium’s ability to polymerize actin filaments at its tail end. Actin is arranged in subunits to form microfilaments that are capable of directing cell movement. L. monocytogenes accomplishes cell motility through a virulence factor called ActA that takes advantage of normal actin polymerization going on in the cell. The ActA protein shares sequence homology with a protein called WASP that is found in virtually all eukaryotic cells. WASP is responsible for recognizing and binding to the Arp2/3 complex. Once they are bound actin filament polymerization is initiated locally because the Arp2/3 complex allows nucleation of actin into long chain filaments. ActA is therefore present only at one end of the bacterium, called the tail end, to direct site-specific actin polymerization. The rocketing movement of L. monocytogenes enables the bacterium to protrude out of one cell and into an adjacent one, evading the immune response.


Symptoms

Symptoms appear following an incubation period of 1-8 weeks, usually 31 days. It is therefore difficult to contain the spread of L. monocytogenes because incubation may be as long as 8 weeks, resulting in numerous asymptomatic individuals. Symptoms of listeriosis include fever, muscle aches, stiff neck, and gastrointestinal symptoms such as nausea or diarrhea. Infection may also spread to the nervous system resulting in symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions. Pregnant women may experience flu-like symptoms while infants may experience pneumonia. Complications from listeriosis are very serious, including mortality rates of 70% from septicemia and 80% from perinatal/neonatal infections. About 20% of individuals infected with listeriosis die from the infection. 

Risk

Those at high risk for infection with L. monocytogenes are primarily pregnant women, newborns and immuno-compromised individuals, including the elderly, patients diagnosed with cancer, AIDS, and diabetes. An infected mother is capable of transmitting listeriosis to her newborn through the placenta. It is believed that healthy adults and children may become infected but rarely develop symptoms of listeriosis or become seriously ill unless contamination is very high. Specifically individuals younger than one year and older than 60 years have the highest incidence rate of infection with L. monocytogenes, 3.9 per 100,000 and 1.7 per 100,000 respectively.


Prevention and Treatment

Many preventative measures can be taken to avoid infection with L. monocytogenes. It is most important to thoroughly cook raw meat and thoroughly wash raw vegetables before consumption. Those at high risk for listeriosis can avoid the following foods: hot dogs, soft cheeses, unpasteurized products, refrigerated meat spreads and refrigerated smoked seafood. Antibiotics can be used to treat L. monocytogenes and those that are most effective include ampicillin, gentamicin, penicillin, and trimethoprim/sulfamethoxizole (Bactrim®, Septa®). Antibiotics, if given early, to the pregnant woman can often prevent infection of the fetus. Babies with listeriosis receive the same antibiotics as adults. Even with prompt treatment, some infections result in death. This is particularly likely in those with central nervous system involvement, the elderly and in persons with other serious medical problems.


Worldwide

Approximately 2,500 cases of listeriosis are reported every year in the United States. This includes 500 preventable deaths. L. monocytogenes outbreaks are still occurring worldwide. Recently, in 2002 contaminated turkey deli meat caused a US outbreak along the east coast and contaminated cheese caused an outbreak in British Columbia. Outbreaks over the past twenty years have involved contaminated chocolate milk, shrimp, lunchmeats, and cheese. A California outbreak in 1985 was due to contaminated Mexican-style cheese. This outbreak led to numerous stillbirths resulting in the monitoring of cheeses by the FDA. Fortunately, according to a study done by The US Department of Health and Human Services, infections with L. monocytogenes have decreased 35 % from 1996 to 2002.