The intention ofthis column is to throw a spotlight on individual ofganisms — not to blind you with science but to reveal aspects of specific plants, animals and microorganisms, isteria monocytogenes is a potentially deadly bacterium. This food-borne pathogen has an amazing ability to survive in a wide range of extreme envitonmenis, including highly acidic and salty surroundings. It can also survive and multiply at temperatures fram 2°C to 45°C. The higher temperature would kill most bacteria. This talent Key NOrESI fr survival makes listeria a dangerous pathogen Listens ise and also an interesting organism for microbiologists athegen nao Phagocytosis ‘°° eM arary aterm foods have been found to carry listeria, including meat, sh, vegetables, cheese and 500 i 3 i Potent no dos 3 450} (i patients who became il | j u 3 400 : | 5 a 350 300 4 250 } 200 | 100 a | Pe | : : i 10 ! es I i oil Smoked Coleslaw Mik Cheese Paté Deli mussels reals Food source Figure 1 Examples of fod-borne outbreaks of sterass in the USA between 1980 and 2000, showing which fads caused the outbreaks and how mary people became le cied iportant and fascinating i eae ale sores. gute 1 shows fwd hat ave town have eee nee ort hve ded ‘The symptoms of an infection with listeria vary depending ‘on who is infected. In healthy people it can simply cause a mild, flu-like illness or diarrhoea, but in vulnerable people the disease can be much more serious, People who are ‘more at-risk include the elderly and those with a reduced immune system. In these people, listeriosis can lead to septicaemia and infections of the central nervous system (CNS) (discussed in the next section). Listeriosis can also be dangerous for pregnant women, as the Dacteria are able to cross the placenta and infect the fetus. Listerial infection can have a fatality rate of up to 30% in at-risk patients but it is still a relatively uncommon infection, with galy around 1200 cases reported in the USA between 19804 BIOLOGICAL SCIENCES FeContaminated re \ Soll tral nervous system Replication in the liver Septiczemia <— Infection of the fetus Fecal ‘across the placenta sheeing Figure 2 The posible paths tat infection with Fistria can take. A Infection causing gastroanteritis (diarrhoea) can develop into the serious forms af istarioss: adult infection, mainly of the CNS, and infection, 2000. This number is very low in comparison with cholera, another diarrhoea-causing bacterium. In the year 2000, alone, the World Health Organization reported 137071 «cases of cholera worldwide. ‘As a food-borne organism, lsteria enters the body via the digestive tract, crossing the epithelium lining in the host's Intestines. Figure 2 shows the two possible routes the infec: tion can take. The first route is the spread of bacteria through the cells in the gut epithelium. This causes gastroenteritis and fever, The second route is the movement of the bacteria across the intestinal epithelium and into the blood. From, here the bacteria can spread around the body and infect other organs, causing more serious illness. An important feature of listeria infection is its ability 10 cross many of the ody’s internal barviers, such as the gut epithelium, the .od-brain barrier and the placenta. This ability to cross Jers gives the bacteria access 1 many different tissues and produces the wide range of symptoms associated with, listeriosis. Immunity and disease Atcrisk patients, who are more susceptible to system. Once the bacteria have spread across the intestinal epithelium, they travel to the liver, where they mukiply. When they reach high numbers they return to the blood and spread around the body. The bacteria most frequently accumulate in the CNS and the uterus in pregnant women, This gives two distinct forms of listeriosis © Adult infection, mainly of the CNS, including meningitis, meningoencephaltis and septicaemia, afection ofthe fetus due to bacterial spread ese iscema using sepccemia nthe cell surface sepremacr 2009 [Attachment of the bacterium to the phagocytic prateins (internalins) on the / fetus, which can lead to meningitis and other CNS disor~ ders. In severe cases it can cause miscarriage or still-birth The mother may have mild flu-like symptoms or no symp: toms at al It is possible to treat listeriosis in both adults and newborns with a combination of antibiotics, including ampicillin, The spread of listeria from the mother to the fetus can sometimes be prevented by rapid treatment of the mother, but this can be difficult as the mother often has no ‘symptoms to suggest she Is infected. Listeria does occasionally infect otherwise healthy patients, especially when they get a high dose of bacteria in, their food. In these cases, the disease is usually manifested as gastroenteritis and fever. It is thought that many cases, of listeria-induced gastroenteritis are misdiagnosed as other infections. Normal sampling methods, such as culturing, bacteria found in patients’ stool samples, do not det listeria, so this form of listeriosis could be more common than previously believed Bacteria do sometimes manage to penetrate the gut epithelium and colonise the liver in healthy individuals via the hepatic-porial vessel. The immune system usually deals, ‘with them before severe infeation can develop, Neutrophils a type of white blood cell that isa phagocyte, enter the liver and attack infected liver cells, They cause the death of these liver cel and release the bacteria into the extracellular envi- ronment, Other neutrophils can then destroy the bacteria, and also form a barrier around the infection, preventing the bacteria spreading around the body. This helps the body to contain and eventually eliminate the infection, Cell entry Listeria sable to colonise many host cel types because of ts ablty to induce phagocytosis in cells that ae not usually ‘hagocytes. Protein called internains, onthe surlace ofthe bacteria, attach to receptors onthe host cells (see Figure 3) Binding of the intemnalins generates a response in the host cel forcing it to take the bacteria into a membrane- bound vesicle caled a phagosome. Normally, a phagosome containing ingested material then fuses with lysosomes Figure 3 Induction of phagocytosis. hs usion of tt phagosome 7 fw the cell membrane and release ofthe debris, Release of toxic enzymes from the Uptake of Iysosomes kills bactrim the bacterium phagosome Fusion of lysosomes with the phagosome, forming a hagolysosome Phagocytic celFurther reading Todar's Online Textbook of Bacteriology www: textbookofbacterology.netLsteria.himl The Centers for Disease Control and Prevent: www.cdle.govmnczvedsafhmd/tisease_listingfistriosis stmt These are another type of membrane-bound vesicle and they contain destructive hydrolytic enzymes that would normally kill the invading bacteria (see BioLocicat Screwces, Rewew, Vol. 17, No. 3, pp. 14-16}, The phagolysosome, formed by the fusion of phagosome and lysosome, then fuses with the plasma membrane and releases the debris, into the extracellular environment (sce Figure 3). Listeria must escape from the phagosome before the lysosomes fuse, orit will be destroyed. Its ability 10 grow and replicate successfully is entirely dependent on escaping from the host cell’s killing mechanisms. So how does it do it? Like many other pathogenic bacteria, listeria produces a toxin that damages the host cell and allows the bacteria to survive. This toxin is called listeriolysin © (LLO). Ie acts by forming large pores in lipid membranes, LLO specifically targets the membrane of the phagosome, causing it to break ‘open and allowing the bacteria to escape into the cyto: plasm. The action of LLO is tightly regulated, preventing it from acting on the host cells surface membrane. It is opti: mally active at acidic pHs, such as those in the phagosome, ‘and inactive at the neutral pH of the cytoplasm. Listeria is Clearly well adapted to its life as an intracellular pathogen, because if LLO attacked the cell membrane, the bacteria ‘would be released from the cell and be exposed to the hosts immune responses Actin-based motility ‘Once listeria has escaped from the phagosome itis free to grow, replicate and move around in the host cell eytoplasm. Listeria has an interesting and almost unique mechanism. for moving about inside the host cell, known as actin. based motility. Actin filaments form part of the host cel igure 4 Transmission electron micrograph of actin filaments attached to istria cell to propel it through the eytoplasmm. Repraguced wth permission fam Gouin, Ee (1999). Ce Sc Vol. 112 Pt 11), pp. 169-708, 8 TERMS exiainea Biood-brain barrier The walls of the blood vessels in the brain are fer less permeable than in ather parts of the body. This helps to protect the brain from foreign substances (such as most bacteria), and to maintain a constant environment in the brain tissue Food-bome pathogen A disease-causing organism that is spread by eating contaminated food. ‘Meningitis Inflammation of the meninges, which are layers of tissue that surround and protect the brain from damage. It can be caused by infection with bacteria, such as listeria, ‘Meningoencephalitis Inflammation of the meninges and the brain. Like meningitis, it can be caused by bacterial Infection, Phagocytes Immune cells specialised in the uptake cf invading microorganisms and foreign molecules into membrane-bound vesicles by a process called phagocytosis ‘Septicaemia Bacterial infection of the blood (often call blood poisoning). Vesicle A small membrane-bound sac found inside cells The membrane is made up of a phospholipid bilayer, which separates the contents of the vesicle from the cytoplasm. Attachment of listeria tothe — host cell surface via internaling ——_ (see Figure 3) Listeria monocytogenes Phagocytosis and uptake of the bacteria into a phagosome Escape from the phagosome into the cytoplasm using the LO toxin Lysis of phagosome ‘and replication in cytoplasm Movement around — the cell using actin-oased motility Double- rmembraned| vesicle Intercellular transfer —| via protrusions from the cell surface membrane, resulting ine double- rmembraned vesicle Escape from the: 1 ouble-membraned vesicle using LLO again Lysis of vesicle Figure 5 Te inracluiar fe ye of liste eo BloLosteAt sciences nevewcytoskeleton — a network of fibres that gives structure 10 Qe 28 pps many ofthe plas vgn MMfn-based motility uses a specific lsterial protein to hijack the host cell’s actin filament extension machinery. This is 2 complex of proteins that extend the actin filaments by adding actin monomers to the chain, Extension of the cells actin filaments With the bacterium attached propels it through the cytoplasm and produces characters ‘act tals’ (Gee Figure 4. This mechanism ean even drive listeria into neighbouring cell via protrusions fom the cell surface membrane. This direct intercellular transfer fs another elec- tive way of evading the host immune system, as bacteria can spread between cells and throughout tissues without becoming exposed to the extracellular environmen avoiding contact with immune cells and antibodies. The complete cycle of cel invasion is summarised in Figure 5. Listeria monocytogenes is an important and extensively studied organism, It has been used as a model fr studying bacterial infections because ofits mechanisms for survival inside and outside the host cell andi suategies or evading immune system. It has also been used as a tool for Sedying the bioldgy of host cells because of the way it interacts with them, An example ofthis use as a model is the binding of internalins to host cell receptors. Despite the fact that listeria Is not a major disease threat, itis still a fascinating and incredibly useful bacterium for mierobiol ogists to study. It provides insights into the way bacterial pathogens case dsease, and how they interact with our bodies. Future work with listeria will enable us to produce Immunofiuarescenc light micrograh of kidney calls S hours after infection with listeria (ed), The bacteria have polymerisea the hosts actin (green) visible on many of thom as characteristic "alls (eb Figures and 5 tat prope them through the call better models to help us understand how some bacterial pathogens work and, perhaps, how to prevent the diseases, they cause, : Frances Medaney is an undergraduate student studying micro biology atthe University of Manchester. She is currently on a 1 year industial placement at the NERC Cerite for Population Biology, working na project about speciation in asexual otgan- isms, before going back te Manchester to complete her final year. We ArT NNT =Yole) eo bd www. philipallan.co.uk/a-zonline tt understanding for the very best grades entries on all key terms niner and author + For more information and sample pages go to www.philipallan.co.uk/a-zonline. You can order online at www.philipallan.co.uk eee To contact our Customer Services Department, telephone 01235 827720. ‘SEPTEMBER 2009 9