Listeria is a genus of bacteria characterized by gram-positive, rod shaped organisms that do not form spores and are facultative anaerobes. This genus currently contains 17 species, 9 of which have been newly described since 2009. Listeria are able to easily grow on a variety of media, and will show beta hemolytic patterns when grown on blood agar. Listeria contain many physical and visual similarities to streptococci and corynebacteria, however they have a few distinct characteristics that distinguish them from these other genera. Listeria species are motile, whereas corynebacteria are nonmotile, and Listeria are also catalase positive, indicating that they produce the enzyme catalase which decomposes hydrogen peroxide into water and oxygen. Catalase is an important feature of these bacteria, because they are intracellular parasites and catalase can protect the cells against damage from reactive oxygen species inside the host cell. A catalase test can distinguish the catalase positive Listeria species from catalase negative streptococci species.
Of the 17 species of Listeria, only two have been indicated as human pathogens that cause listeriosis; Listeria monocytogenes and Listeria ivanovii. These species are able to grow at very low temperatures, as low as 4°C, which contributes to the epidemiology and spread of these bacteria. Their ability to form biofilms also makes it difficult to decontaminate products meant for human consumption that could possibly be infected by Listeria. L. ivanovii has been indicated in a few cases of listeriosis in humans on other continents, however L. monocytogenes is much more commonly indicated as the species present in patients with listeriosis.
Epidemiology
Listeria monocytogenes is widespread in animals such as cows, pigs, birds, and rodents, and in soil, decaying vegetation, stagnant water, and other natural habitats. Transmission from these sources to humans occurs by eating unpasteurized dairy products, dairy products that have been contaminated post pasteurization due to cross contamination with still infected sources, and by contact with infected animals or their feces. The contamination of dairy products results in spread of L. monocytogenes due to this organism’s ability to survive in low temperatures. Therefore it can still grow and thrive in the usual refrigerated environment of these products.
The CDC website lists 13 important outbreaks of listeriosis since 2011, all of which were caused by contaminated dairy products or produce that were most likely infected by Listeria in the soil or nearby animal feces. There are about 1,600 cases every year in the United States, with about 260 deaths attributed to listeriosis each year. An outbreak in the fall of 2011 due to contaminated cantaloupes from a farm in Colorado resulted in 147 cases and 33 deaths. This outbreak was the deadliest so far and was the first outbreak of Listeria infection that resulted from contaminated produce. The largest reported outbreak before the 2011 incident occurred in Los Angeles County, California in 1985, after a number of people ate a soft Mexican style cheese and were infected; this outbreak resulted in 142 cases and 48 deaths.
Description of Disease
Listeriosis is the primary human disease caused by Listeria. As previously discussed, transmission of the bacteria Listeria can occur by eating contaminated dairy products or produce, or by contact or consumption of contaminated animals. Due to being a food borne illness, clinical manifestations of listeriosis can present initially as gastrointestinal distress. Vomiting, nausea, diarrhea, and fever can occur. However, often the disease does not present clinically until it becomes systemic, resulting in septicemia or meningitis in non-pregnant individuals.
The most susceptible individuals to this disease are the elderly, immunocompromised, pregnant women, fetuses, and newborns. Listeriosis has a very high rate of maternal/neonatal cases, meaning both the mother and the fetus or newborn will be infected. This is due to the ability of L. monocytogenes to transmit transplacentally. Pregnant women typically only exhibit mild flu-like symptoms and muscle soreness, however the disease can result in stillbirth, miscarriages, or premature labor. If the infant does survive to birth, they can have very severe infections such as encephalitis or meningitis.
Pathogenesis
L. monocytogenes is an intracellular pathogen that resides in non-immune macrophages. The bacteria are able to facilitate uptake into the host cell by regular phagocytosis. Once endocytosed, the bacteria escape the phagosome by way of important virulence factor listerolysin O (LLO), a membrane damaging toxin. The bacterium is able to escape the phagosome before it has a chance to merge with the host cell lysosome, thus avoiding degradation and death by the acidic contents of the lysosome. L. monocytongenes can then proliferate in the cytosol. Although L. monocytogenes is motile at room temperature and colder, at 37°C inside the host cell, their flagella are not expressed and the bacteria have to rely on the structural components of the host cell to move around and invade other cells.
The bacteria induce a reorganization of actin in the cytoskeleton of the host cell, and small actin monomers concentrate behind the cell and create the appearance of a comet-like ‘tail’. These actin filaments facilitate the movement of the bacteria to the periphery of the cell, where they push against the membrane and create a protrusion that is then taken up by a neighboring cell. The organisms are now surrounded by a double layered membrane inside of the next host cell, where they degrade the membrane again using LLO, and are now able to infect the next cell. This ability to move laterally from cell to cell is similar to the mechanisms of Rickettsia sp., Shigella sp., and some types of E. coli. This factor contributes to the pathogenesis of the bacteria because they are able to evade the immune system by moving completely intracellularly. The process continues until the bacteria reach the bloodstream, which is what results in the systemic presentation of listeriosis.
Diagnosis
L. monocytogenes infection can be diagnosed by a bacterial culture of tissue, blood, or cerebrospinal fluid. The organism can also be isolated from lesions present on the patient. The culture on a blood agar plate will show beta hemolysis, and microscopically the motility and morphology will distinguish the organism from other pathogens that cause similar symptoms.
Treatment and Prevention
Listeria infections are treatable with certain antibiotics. Ampicillin and trimethoprim/sulfamethoxazole have proven successful treatment, and in patients with impaired T cell function ampicillin combined with gentamycin has also shown to be successful in treating infection.
There is no vaccine to prevent Listeria infection, however there are measures that can be taken to prevent infection before it happens. Due to the severity of diseased caused by L. monocytogenes, regulations and decontamination procedures have been edited and standardized in a way to greatly reduce the amount of contamination in packaged meat products and dairy products. However, properly cooking and handling meat products and avoiding unpasteurized dairy products can greatly reduce the chance of coming into contact with Listeria species and therefore prevent infection with listeriosis.
Klebsiella: a Synopsis
Description of Organism
Klebsiella is a genus of bacteria comprised of gram-negative, rod shaped bacteria, which are non-motile and are facultative anaerobes. Most species have a prominent capsule, resulting in a mucoid appearance when grown on plates. There are three species of Klebsiella that are considered to be important pathogens in human disease: Klebsiella pneumoniae, Klebsiella granulomatis, and Klebsiella oxytoca.
Klebsiella species are part of the normal microflora of humans and are commonly found in the oropharynx and gastrointestinal tract of humans. Despite this, they can behave as opportunistic pathogens in immunocompromised individuals.
Epidemiology
Klebsiella species colonize many parts of a healthy human body, however if the individual has a compromised immune system the pathogen can take over and cause infection and disease. Klebsiella species have been implicated in many community acquired and nosocomial infections. In community-acquired infections, commonly infected groups are the elderly and individuals with alcoholism. K. pneumoniae is a principal cause of pneumonia in elderly populations, with infection rate indicated in different studies to be 15%-40%. It is also a major cause of nosocomial infections, with reports of implication in anywhere from 3-7% in the United States.
Klebsiella has an extremely high mortality rate, up to 50% mortality even in healthy individuals. In those with alcoholism or compromised immune systems, that number approaches 100%. There have been many outbreaks reported of Klebsiella infection, and most recently these have been comprised of antibiotic resistant strains, such as carbapenum resistant Klebsiella (CPRK).
Description of Disease
K. pneumoniae manifests as many diseases, such as pneumonia, urinary tract infections, bacteremia, septicemia, diarrhea, and meningitis. It can also cause soft tissue infections. Symptoms of pneumonia caused by this bacteria are similar to symptoms of other bacterial pneumonias. A productive cough with thick yellow or green mucus, chest pain, chills, and a high fever are all indicators of a possible bacterial pneumonia. Symptoms of a urinary tract infection caused by K. pneumoniae are also similar to UTIs caused by other bacteria. Frequency, burning, and urgency of urination, along with possible abdominal pain can be symptoms of this infection.
Pathogenesis
The main factor in pathogenicity of K. pneumoniae is the polysaccharide capsule. This allows the bacteria to evade the host immune system by recognition and also by inhibiting the activation of complement because of the difficulty of deposition of C3b on a capsule. The bacteria also produce many different types of adhesins, each of which with its own receptor specificity. These adhesins allow for adherence of the bacteria to the host cell, which then facilitates invasion of the host cell.
The LPS of K. pneumoniae is also an important virulence factor. They activate complement to deposit onto certain sites that do not contribute to pathogen death because the membrane attack complex is not able to form so the bacteria survive.
Diagnosis
Klebsiella can be most commonly isolated from sputum samples or blood. K. pneumoniae will appear as short bacilli and gram negative. The capsule is also sometimes visible as a clear spot around the bacillus. K. pneumoniae can also be found in urine in the case of UTIs and in lesion samples in soft tissue infections. It does not require any special media to grow.
Further tests required to diagnose the infection as K. pneumoniae are an indole test, urease test, TSIA slant, and lactose-fermenting test. The bacteria does ferment lactose, will result in a negative indole test, and positive urease test, and on the TSIA slant will show an acidic butt and slant, with gas production but no H2S production.
Treatment and Prevention
There is no current vaccine to protect against K. pneumoniae infection. Prevention can only be facilitated by proper decontamination procedures in hospitals and careful hygiene in communities.
Treatment involves choosing the right antibiotic for the system that is being affected. Unfortunately, K. pneumoniae has developed resistance to multiple different antibiotics, probably a plasmid-mediated characteristic. Extremely ill patients should be treated with cephalosporins, carbapenems, aminoglycosides, or quinolones. These agents can be used as monotherapy or combination therapy. Ceftazidime and avibactam combination therapy should be used to treat patients that have abdominal infections such as UTIs. These antibiotics are effective against infections with resistance to carbapenems.