OUP user menu

History and epidemiology of listeriosis

H. Hof
DOI: http://dx.doi.org/10.1016/S0928-8244(02)00471-6 199-202 First published online: 1 April 2003

Abstract

Listeriae are used as a tool by different specialities in biomedical research. There are now at least four major fields of interest in Listeria: (1) the role in medical microbiology: Listeria monocytogenes causes severe diseases of men and animals and is difficult to treat; (2) the role in food microbiology: Listeria is a food-borne pathogen and is found in various food items; (3) the role in cell biology: L. monocytogenes is a facultative intracellular parasite having an intense cross-talk and interactions with the host cell; (4) the role in immunology: basic knowledge on cell-mediated immunity has been acquired through the model of listeriosis. This paper presents information on the past and the actual situation in research on Listeria and listeriosis.

Keywords
  • Listeria
  • Listeriosis
  • Listeria monocytogenes
  • Food microbiology
  • Immunology

1 The detection

When in 1924 E.G.D. Murray isolated Gram-positive rods from the blood of laboratory animals, i.e. rabbits, he could not assign these pathogenic microorganisms to any bacterial genus known at that time. Thus, he called this new agent Bacterium monocytogenes[1]. It can be anticipated that, even before Murray, other bacteriologists had already grown this particular bacterium without having a clear classification. In 1940 Pirie [2] named the genus Listeria for catalase-positive, Gram-positive rods. This had become necessary, because in the meantime such bacteria had been isolated in some other cases from humans [3], from animals as well as from food and the environment. These incidental observations did not, however, establish a broad awareness about this pathogen in the community of infectious disease specialists, microbiologists or food microbiologists.

2 The pathogenic potency

The particular role of this type of bacteria as a pathogen was not realized until an epidemic of listeriosis in newborns occurred in Germany in 1949. In the Institute of Pathology of the University of Halle a peculiar entity was observed, hitherto unknown and called ‘granulomatosis infantiseptica’. In 85 newborns or stillborn infants granulomas were detected histopathologically in various organs such as liver, spleen, brain, lung and skin. A young bacteriologist, J. Potel, was able to isolate bacteria from meconium, blood or various organs; he classified them in the genus Corynebacterium[4]. At about the same time similar cases of connatal infections were observed and studied at the University of Bonn. The bacteria isolated from these lesions were examined by H.P.R. Seeliger [5]. He detected the motility of these pathogens, which was not consistent with Corynebacteria but rather with Listeria.

At that time a new era of research on listeriosis started. In the following years Seeliger invested an enormous effort to inform the public about Listeria and listeriosis. He compiled the first overview in the book ‘Listeriosis’[5], which is still the classical, nearly biblical publication. But he was not only the pioneer of Listeria research: later on he consistently pursued this matter and he reported about new developments on various occasions so that he became the master of listeriosis research. One of these activities resulted in the organization of the proceedings of a workshop in Izmir in 1988 [6].

Today, it is known that Listeria monocytogenes is pathogenic not only to human individuals but also to animals. L. monocytogenes has been cultivated from many species including virtually all domestic and wild animals and birds, but not from fish (with a few exceptions).

3 Genetics

Seeliger gathered a collection of about 6000 Listeria isolates which he obtained from all parts of the world, the majority originating from patients or animals. A minority, however, originated from environmental sources. All these strains were similar, so that for many decades it was suggested that there is only one single species in the genus Listeria, namely L. monocytogenes. By means of specific antibodies directed against O-antigens (i.e. teichoic acids) in the cell wall as well as proteinaceous H-antigens on flagella, more than 60% of the strains could be arranged into certain serovars. About 90% of the isolates deriving from human patients belong to either serovar 1 or 4. It has been observed, however, that some particular strains, mainly among members of serovars 5 and 6, were somewhat different. Rocourt [7] was the first to separate L. monocytogenes (sensu stricto) from other Listeria species by means of biochemical methods and later by genetic comparison. Whereas nearly all strains of L. monocytogenes were shown to be pathogenic, all other species including Listeria innocua, Listeria seeligeri, Listeria welshimeri, and Listeria ivanovii were practically non-pathogenic. However, not all strains of L. monocytogenes are created equal [8].

In an exemplary manner, an international group of researchers [9,10] characterized a gene cluster on the bacterial genome, which was responsible for the pathogenicity, a so-called pathogenicity island. The roles of several pathogenicity factors such as hemolysin (listeriolysin), phospholipases and actin activating protein were elucidated [9]. Recently, an international consortium sequenced the whole genome of L. monocytogenes[11].

4 A food-borne disease

Another keystone in listeriosis research was the observation of Schlech et al. [12] that a listeriosis outbreak in Halifax, Canada was transmitted via infected food, namely coleslaw. Although the oral route of infection was described in the original publication of Murray et al. [1], L. monocytogenes was not included in the list of bona fide food-borne pathogens until this Canadian experience. Food-relatedness was confirmed in the 1980s by the occurrence of several other outbreaks in the USA and Switzerland, due to cheese. In retrospect, the concept that food, for example spoiled silage, could be a major source of animal infections had been proclaimed long before.

Many different food items have been incriminated to transmit Listeriae (Table 1) [13].

View this table:
Table 1

Food safety

Food items which may contain L. monocytogenesFood items which in general are free of Listeriae
Sausages (salami, paté)All kinds of food immediately after heating
Raw meat, in particular turkey and chickenPasteurized milk, yoghurt (industrial products!)
SandwichesHard cheese
Lettuce, raw mushroomsChocolate, marmalade, cookies
Raw milk and products made from this materialRaw carrots
Soft cheese (Munster, Roquefort, Camembert, Brie)Raw apples
Fresh cheese (ricotta, feta)Raw tomatoes
Seafood (mussels, salmon)
All kind of meals which are conserved after having been heated

Lactating cows can shed L. monocytogenes in milk as a consequence of mastitis for a rather long time. Thus, the pathogens can be present in the original foodstuff. In addition, it can even happen that Listeriae enter the food chain during processing. Soft cheese such as Camembert can be contaminated on the surface during ripening; the microorganisms can be transferred by various utensils, for example the wooden trays on which they are stored. As has been documented several times, contamination may occur during the production of other foods, such as salmon, in the processing plant. In consequence, the food industry has to adhere to the principles of hazard analysis of critical care points to avoid or minimize the risk to the consumer [13].

Nowadays it is well known that listeriosis is a food-borne disease. There is scant evidence that a mild and transient gastroenteritis may precede overt disease [14]. Obviously, this exposure to pathogenic Listeriae is rather common, since more than 90% of adults possess immune lymphocytes. Whereas most normal, immunocompetent individuals will overcome an initial attack and shedding of Listeriae by feces is terminated after a few days, people at risk (Table 2) may suffer from disseminated infection. Sepsis, meningitis and/or encephalitis occur in most instances, however, many other clinical manifestations have been described.

View this table:
Table 2

People at risk

Incidence of listeriosis in certain populations at risk (per 100,000 individuals per year)
Normal population0.7
Aged persons (>70 years)2
Alcoholics5
Diabetic people5
Iron overload5
Pregnant women12
Cancer patients15
Steroid therapy20
Lupus erythematodes50
Kidney transplant recipients100
Chronic lymphatic leukemia200
AIDS600
Leukemia (acute monocytic+acute lymphoblastic)1000

A particular disposition is imposed by pregnancy. Pregnant women have a 12-fold increased risk in comparison with the normal population to acquire listeriosis after consumption of contaminated food. Although the mother herself will pass through a mild, flu-like, febrile episode, the pathogenic bacteria having access to the circulation will colonize the placenta, induce a placentitis and hence infect the defenseless fetus. Connatal infection will result in either stillbirth or early-onset listeriosis. The prognosis of this infection is rather poor. Less dangerous is the late-onset listeriosis of newborns, who acquire the pathogens during labor or shortly after birth either from the mother or as a nosocomial infection [15].

5 A model for immunology

A strong immune defense is essential to overcome a Listeria infection. Mackaness and his group [16] at Saranac Lake in USA have studied the non-specific and immunologic mechanisms contributing to resistance to L. monocytogenes. The mouse model in particular has provided an excellent tool to study the relative role of the partners, such as macrophages and lymphocytes [16]. T-lymphocytes are essential to enable a host to develop granulomas with a definite anti-listeric power.

6 The intracellular habitat

Listeriae can grow in the environment as well as in the extracellular space within a host. However, they belong to a group of bacteria that are able to penetrate into, and to survive and multiply within host cells (Fig. 1), not only in professional phagocytes but also in virtually every nucleated cell of the body. By means of factors such as internalin A and/or B the host cells are triggered to internalize the attached bacteria. Inside a host cell the pathogenic bacterium produces hemolysin and phospholipases and it can leave the phagocytic vacuole and enter the cytoplasm. Once in the cytosol, pathogenic strains will polymerize actin from the host cell cytoskeleton. This happens mainly at the apical tip of a bacterium so that the new actin filaments act like a driving force; the bacterium moves around in the host cell until it by chance gets under the surface of the host cell. This contact induces the host cell membrane to produce extrusions which penetrate a neighboring host cell. The second host cell can engulf these ramifications containing the living L. monocytogenes. Hence, the bacterium will lyse the double cell membrane and invade the cytoplasm of the second host cell. By this mechanism of cell-to-cell spreading the intracellular parasite avoids the host cell's defense mechanisms [9].

Figure 1

Strategies of different facultative or obligate intracellular bacteria to survive within host cells.

The intracellular habitat of L. monocytogenes is the consequence of an intense cross-talk between host and parasite. The deciphering of this communication can help bacteriologists as well as cell biologists to understand the underlying biological mechanisms. Because of this, Listeria has become a highly appreciated tool in cell biology [9].

7 Summary

From 1926 to 1950 only sporadic reports on Listeria were published resulting in only few well-informed specialists. Since then a great deal of information about Listeria and the host reaction has reached the scientific community. Today investigation of Listeria is a modern field in biomedical research. Listeriae provide a tool for different specialists in biomedical research, including but certainly not restricted to medical microbiologists and medical doctors.

Footnotes

  • E-mail address: herbert.hof{at}imh.ma.uni-heidelberg.de (H. Hof).

References

  1. [1].
  2. [2].
  3. [3].
  4. [4].
  5. [5].
  6. [6].
  7. [7].
  8. [8].
  9. [9].
  10. [10].
  11. [11].
  12. [12].
  13. [13].
  14. [14].
  15. [15].
  16. [16].
View Abstract