Hospital+Killers+Pseudomonas+aeruginosa


 * Hospital Killer: //Pseudomonas aeruginosa// **

Author: Jake Burns Date: 5/16/2010

**Introduction:** Gram negative bacteria are the cause of thousands of hospital acquired (also known as nosocomial) infections each year. It is estimated that approximately 30% of all hospital acquired infections are caused by gram negative bacteria, and that they are responsible for approximately 70% of all hospital acquired infections contracted in the Intensive Care Unit, data for the United States (Peleg and Hooper, 2010). These bacteria are classified by their reaction to a test called a gram-stain test, which was developed by Hans Christian Gram in 1884 (Sutton 2006). Gram negative bacteria differ from gram positive bacteria because they have a lipposaccharide layer surrounding their cell wall and only a small amount of peptidoglycan (Costerton, Ingram, & Cheng 1974). This research paper will outline the basic structure of gram negative bacteria and then will give an in depth look at the bacterium //Pseudomonas aeruginosa (P. aeruginosa)//, which is one of the prominent bacteria that cause hospital acquired infections. This paper will give a brief overview about how //P. aeruginosa// operates, how it is transmitted to patients in the hospital setting, the mechanisms it uses to infect its host, how it acquires its resistance to antibiotics, treatment and prevention, and finally what happens when //P. aeruginosa// becomes multidrug resistant.


 * Gram negative bacteria: The cellular envelope **

The reason why many gram negative bacteria are resistant to various types of antibodies and the reason why they can grow almost anywhere is because of the extracellular envelope that surrounds the cell. This cellular envelope is composed mostly of lipopolysaccharide. The chemical makeup and parts of the envelope are extremely complex, but the most important part about the envelope is its ability to protect gram negative bacteria by limiting its permeability to outside sources of harm. This envelope closely regulates what goes in and out of the cell, which makes it impossible for many antibiotics and antibodies to get inside the cell to destroy it (Costerton, Ingram, & Cheng 1974). This extra layer of protection has made gram negative bacteria extremely difficult to treat due to the antibiotic resistant nature of the envelope. For a more detailed look at the gram negative cell envelope go to: []


 * // Pseudomonas aeruginosa //**** : An overview **

//Pseudomonas aeruginosa// is an opportunistic pathogen that is gram negative, is a facultative anaerobe (when O2 is not present it can use NO3 as a final electron acceptor in respiration), is bacillus, and a member of the Gamma Proteobacteria//. P. aeruginosa// is commonly found on many different surfaces including: in soil, water, plant surfaces, and even on animals and humans. It is motile with a single polar flagellum, and is one of the fastest bacteria seen in hay infusions and pond water samples. //P. aeruginosa// has very few nutritional needs and can even be found growing in distilled water! //P. aeruginosa// can be found in biofilms or as a single bacterium. //P. aeruginosa// is a serious problem in the clinical setting because it is extremely resistant to antibiotics. Since //P. aeruginosa// is gram negative (which makes it resistant to many antibiotics) and because it is highly adaptable, which allows it to live in a wide variety of environments, //P. aeruginosa// can contaminated almost anything. This ability allows //P. aeruginosa// to be an extremely dangerous pathogen in hospitals because it can infect people who have compromised immune systems, such as trauma victims and patients with AIDS. Four out of every 1000 patients is infected by //P. aeruginosa//, and it accounts for about 10% of all hospital acquired infections. When it infects cancer patients, patients with cystic fibrosis, or burn patients the mortality rate is nearly 50 percent (Todar 2008). This is a picture of a color enhanced scanning electron mircrograph of //P. aeruginosa.// **How //P. aeruginosa// is contracted:**

//Pseudomonas aeruginosa// is an opportunistic pathogen that very rarely infects a host whose immune system is healthy. However, when the immune system is compromised, such as in AIDS victims or people in the Intensive Care Unit (ICU), infection becomes a serious health risk. Since //P. aeruginosa// is commonly found in water it can be transmitted to a hospital patient through ingestion, bathing, insertion of contaminated medical devices, or through contact with contaminated surfaces. //P. aeruginosa// can also infect a patient if it is eaten since it commonly lives on the surfaces of fruits and vegetables due to soil contamination. //P. aeruginosa// is also of particular concern because it can live on a surface for up to 16 months! If contamination occurs then it is likely a patient will become infected (Pseudomonas Aeruginosa Fact Sheet).


 * Mechanism of Action: How it Infects **

//P//. //aeruginosa// can cause respiratory track infections, urinary track infections, pneumonia, and many other diseases. This wide range of virulence makes //P. aeruginosa// an especially dangerous bacterium (Slama 2008). When //P. aeruginosa// is introduced to a host the infection can be broken down into three different steps: bacterial attachment and colonization, local invasion, and dissemination and systemic disease (Todar 2008). First we will look at bacterial attachment and colonization.


 * Attachment and Colonization:**

//P. aeruginosa// is a bacterium that can infect various different types of epithelial cells. It uses its pili to adhere to the host’s cell wall and when there are no sites to adhere to the bacteria produces protease enzymes to degrade the fibronectin, which exposes more receptor sites for the pili to adhere to it. Due to the wide range of virulence that //P. aeruginosa// has there are various sites that it can adhere to. These sites are galactose, mannose, or sialic acid receptors that are on the epithelial cell (Todar 2008). The bacterium can form biofilms on the host’s cells, and through these biofilms they are given protection and are able to communicate through quorum-sensing. They can also actively transfer genes through gene horizontal gene transfer (Ueda & Wood 2009).


 * Local Invasion:**

After //P. aeruginosa// attaches and colonizes a host’s cell it begins to produce extracellular enzymes and toxins in order to break down the host cell and invade it. //P. aeruginosa// produces two protease enzymes, named elastase and alkaline aprotease, which help destroy the hosts fibrin and elastin structures. Three other extracellular proteins that //P. aeruginosa// makes are: cytotoxin, phospholipase and lecithinase. Cytotoxin is a pore-forming protein and phospholipase and lecithinase act in a synergistic manner in order to break down lipids and lecithin. The job of all of these extracellular enzymes and toxin is to break down physical barriers of the host’s cell to allow the bacteria to take over the host cell (Todar 2008). There are many other extracellular proteins and toxins produced, and the ones mentioned do a variety of things in a complex manner. However, in order to save time and space the complexities of these will not be discussed further. If you are interested in further research here are some helpful links: [] [] []

media type="youtube" key="ghwoPwJm-D8" height="385" width="480" align="right" //Pseudomonas aeruginosa// can cause blood contamination and systemic disease when dissemination occurs. Dissemination is when something gets scattered or wide spread (Dictionary.com). //P. aeruginosa// lyses the host cell and the toxins that it produces spread throughout the body causing systemic disease, which is often fatal. One toxin that //P. aeruginosa// makes is exotoxin A, which is highly toxic and fatal to humans in large amounts. Exotoxin A is highly dangerous because it stops the synthesis of proteins in infected cells. It is not really clear how exactly //P. aeruginosa// causes its victims to die or how it causes systemic disease, but it is believed that the toxins produced in the local infection phase play an important role of the host death (Pollack 1984).
 * Dissemination and Systemic Disease:**

Here is a helpful video that outlines the mechanism of infection for //P. aeruginosa//. Start the video at 1 minute to skip unnecessary parts.

This video was taken from youtube.com [] ** Antibiotic Resistance: **

//P. aeruginosa// is an especially resistant gram negative bacterium. It has a gram negative envelope that does not allow for many antibiotics to get inside of the cell and the formation of biofilms help protect it by encasing it in a protective alginate polysaccharide. However, it also has unique methods of coping with new antibiotics. Most antibiotics cannot enter //P. ae////ruginosa// because of its lipopolysaccharide layer, and the few who can have to use channels called porins (which are barrel shaped proteins that allow for molecules to cross the membrane) to enter. However, even when these antibiotics, such as beta-lactams, enter the cell //P. aeruginosa// produces proteins, such as beta-lactamase, which then degrades the antibiotics. //P. aeruginosa// has four different antibiotic efflux systems that get rid of any antibiotics that enter the cell before the antibodies can have any effect (Lambert 2002). This video will give you a visual representation of what efflex pumps do.

media type="youtube" key="g9iOkXfTfFM" height="229" width="288" align="center"

This video was taken from youtube.com [] On top of the efflux pumps, cellular envelope, and biofilms there are also other ways that //P.// //aeruginosa// can become resistant to new antibiotics. //P. aeruginosa// has antibiotic resistant plasmids that it can transfer through horizontal gene transfer (Todar 2008). This exchange of gene transfer can facilitate mutations that will allow for more antibiotic resistance. Such mutations lead to reduction of porin channels (which antibiotics need to enter the cell) and many other mutations that will increase drug resistance (Slama 2008). Some strains of //P. aeruginosa// are so resistant to antibiotics that there is no known cure for them. This ability to mutate and adapt to new antibiotics makes //P. aeruginosa// an extremely dangerous pathogen, and the more antibiotics that are used on it the more resistances that it acquires.

Since //P. aeruginosa// is so resistant to many antibiotics it is extremely difficult to cure. There are antibiotics that are given to help people with //P. aeruginosa// infections, but there is no guarantee that these drugs will work. For some strains there is no cure because it has become resistant to all forms of known antibiotics. The best way to minimize deaths because of //P. aeruginosa// is to prevent the infection from happening. Hospitals can ensure that the water they use for bathing, cleaning equipment, and anything else is disinfected. Use sterile solutions to clean medical equipment and cook all fruits and vegetables because they may have //P. aeruginosa// on them. Practice good hygiene to ensure that there is no unnecessary contamination. Lastly hospitals have to be careful with what antibiotics they administer because //P. aeruginosa// will become more resistant if they use the wrong ones (Pseudomonas Aeruginos Fact Sheet** ) **.
 * Treatment and Prevention **:


 * What happens when //P. aeruginosa// becomes multidrug resistant: **

When //P. aeruginosa// becomes multidrug resistant there are severe consequences. One study showed that when people developed this form of //P. aeruginosa// they had a 44% higher mortality rate than people who had a normal //P. aeruginosa// infection//.// The people who acquired multidrug resistant //P. aeruginosa// also had to stay, on average, 17 more days in the hospital and it cost 31,196 dollars, on average, more to treat them than someone without multidrug resistant //P. aeruginosa// (Slama 2008).


 * Conclusion: **

//Pseudomonas// //aeruginosa// is a very dangerous opportunistic pathogen. Due to its highly adaptable nature it is able to develop resistance to many antibiotics, and is therefore extremely hard to cure. This bacterium will continue to be a cause for concern in the medical profession, and more research will have to be done with //P. aeruginosa// to try and find a way to kill the multidrug resistant strains. There needs to be better prevention techniques in hospitals in order to minimize the people who become infected with this bacterium, especially in the ICU, where people are more susceptible to infection. //P. aeruginosa// is a ruthless killer and is defiantly worthy of the title Hospital Killer.

Literature Cited:
 * Costerton, J. W., J. M. Ingram, and K. J. Cheng. "Structure and FUnction of the Cell Envelope of Gram-Negative Bacteria." //Bacterial Reviews// 38 (1974): 87-110. American Society for Microbiology. Web. 16 May 2010. .
 * "Disseminate | Define Disseminate at Dictionary.com." //Dictionary.com |//. Web. 16 May 2010. .
 * Lambert, P. A. "Mechanisms of Antibiotic Resistance in Pseudomonas Aeruginosa." //Journal of the Royal Society of Medicine// 41st ser. 95 (2002): 22-26. //Journal of the Royal Society of Medicine//. 2002. Web. 16 May 2010. .
 * Peleg, Anton Y., and David C. Hooper. "Hospital-Acquired Infections Due to Gram-Negative Bacteria." //The New England Journal of Medicine// 19th ser. 362 (2010): 1804-813. //New England Journal of Medicine//. Web. 17 May 2010. .
 * Pollack, Matthew. "The Virulence of Pseudomonas Aeruginosa." //Reviews of Infectious Disease// 3rd ser. 6 (1984): S617-626. //Jstor//. The University of Chicago Press. Web. 15 May 2010. .
 * "Pseudomonas Aeruginosa." //Special Pathogens Laboratory//. Web. 16 May 2010. .
 * Slama, Thomas G. "Gram-negative Antibiotic Resistance: There Is a Price to Pay." //Critical Care// 4th ser. 4 (2008). //Critical Care//. BioMed Central Ltd, 21 May 2008. Web. 16 May 2010. .
 * Sutton, Scott. "The Gram Stain." //PMF Newsletter// (2006). //The Microbiology Network//. Web. 16 May 2010. .
 * Todar, Kenneth. "Pseudomonas Aeruginosa." //Online Text Book for Bacteriology//. 2008. Web. 15 May 2010. .