Senin, 20 Agustus 2018

Pseudomonas aeruginosa

         Pseudomonas aeruginosa is a gram-negative, rod-shaped, asporogenous, and monoflagellated bacterium that has an incredible nutritional versatility. It is a rod about 1-5 µm long and 0.5-1.0 µm wide. P. aeruginosa is an obligate respirer, using aerobic respiration (with oxygen) as its optimal metabolism although can also respire anaerobically on nitrate or other alternative electron acceptors. P. aeruginosa can catabolize a wide range of organic molecules, including organic compounds such as benzoate. This, then, makes P. aeruginosa a very ubiquitous microorganism, for it has been found in environments such as soil, water, humans, animals, plants, sewage, and hospitals. In all oligotropic aquatic ecosystems, which contain high-dissolved oxygen content but low plant nutrients throughout, P.aeruginosa is the predominant inhabitant and this clearly makes it the most abundant organism on earth.
Scanning Electron Micrograph of Pseudomonas aeruginosa. From the Centers for Disease Control and Prevention (CDC).P. aeruginosa was first described as a distinct bacterial species at the end of the nineteenth century, after the development of sterile culture media by Pasteur. In 1882, the first scientific study on P. aeruginosa, entitled “On the blue and green coloration of bandages,” was published by a pharmacist named Carle Gessard. This study showed P. aeruginosa’s characteristic pigmentation: P. aeruginosa produced water-soluble pigments, which, on exposure to ultraviolet light, fluoresced blue-green light. This was later attributed to pyocyanine, a derivative of phenazine, and it also reflected the organism’s old names: Bacillus pyocyaneus, Bakterium aeruginosa, Pseudomonas polycolor, and Pseudomonas pyocyaneus (3). P. aeruginosa has many strains, including Pseudomonas aeruginosa strain PA01, Pseudomonas aeruginosa PA7, Pseudomonas aeruginosa strain UCBPP-PA14, and Pseudomonas aeruginosa strain 2192 (5). Most of these were isolated based on their distinctive grapelike odor of aminoacetophenone, pyocyanin production, and the colonies’ structure on agar media.
          P. aeruginosa has the genome size of about 5.2 to 7 million base pairs (Mbp) with 65% Guanine + Cytosine content. It is a combination of variable accessory segments and a conserved core. The variable accessory genome is characterized by a set of genomic islands and islets from a primeval tRNA-integrated island type. The core genome consists of a low level of nucleotide divergence of 0.5% and a conserved synteny of genes, which means two or more genes, whether they are linked or not, are on the same chromosome.
Pseudomonas aeruginosa PA01 genome. From the Pseudomonas Genome Database P. aeruginosa has a single and supercoiled circular chromosome in the cytoplasm. It also carries a lot of chromosome-mobilizing plasmids that are very significant to the organism’s lifestyle as a pathogen. The plasmids, TEM, OXA, and PSE, for instance, are encoded for betalactamase production, which is necessary for its resistance to antibiotics, thus allowing P. aeruginosa to be a formidable pathogen.The two strains that have the complete genome sequence are Pseudomonas aeruginosa PA01 and Pseudomonas aeruginosa PA14:
        In 2000, a group of volunteer "Pseudomonas scientists", including those from the Washington PathoGenesis Corportaion and the Department of Biology of the University of California, San Diego, worked under the Pseudomonas aeruginosa Community Annotation Project (PseudoCAP) to publish the complete genome sequence of Pseudomonas aeruginosa PA01. This was done because knowing the genomic sequence would provide new information about this bacterium as a pathogen and about its ecological versatility and genetic complexity. At 6,264,403 base pairs, its bacterial genome is the largest to ever be sequenced. It also contains 5,570 predicted open reading frames (ORFs), and thus it almost has the genetic complexity of simple eukaryotes, such as Saccharomyces cerevisiae. Using whole-genome-shotgun sampling, the complete 6.3 Mbp genome of Pseudomonas aeruginosa PA01 is very much similar to the P. aeruginosa’s physical map, with only one major exception, which is the inversion of about a quarter of the Pseudomonas aeruginosa PA01 genome. This inversion comes from the homologous recombination of the rrnA and rrnB loci, and earlier studies on genomic sequence inversions of ribosomal DNA loci in S. typhimurium and E. coli suggest that this inversion might have adaptive significance.
        The complete genome sequence of Pseudomonas aeruginosa PA14 is currently being done by Harvard Medical School scientists. The goal of this study is achieve a public data of Pseudomonas aeruginosa PA14 genome. The shotgun-sequencing phase of the project was finished in 2005, yielding 6.54 Mbp of PA14 sequence. It is currently being compared to the genome of Pseudomonas aeruginosa PA01 and preliminary results have shown that they are very similar but have several regions of marked differences, such as the insertion of the 107911bp in PA14, which is absent in PA01. Approximately, there is 96.3% of the DNA sequence of PAO1 is in PA14, and 92.4% of PA14 DNA sequence is in PA01 .
        Protein F--Since P. aeruginosa is a Gram-negative microbe, it has an outer membrane which contains Protein F (OprF). OprF functions as a porin, allowing certain molecules and ions to come into the cells, and as a structural protein, maintaining the bacterial cell shape. Because OprF provides P. aeruginosa outer membrane with an exclusion limit of 500 Da, it lowers the permeability of the outer membrane, a property that is desired because it would decrease the intake of harmful substances into the cell and give P. aeruginosa a high resistance to antibiotics.
Flagellum and Pili--P. aeruginosa uses its single and polar flagellum to move around and to display chemotaxis to useful molecules, like sugars. Its strains either have a-type or b-type of flagella, a classification that is based primarily on the size and antigenicity of the flagellin subunit. The flagellum is very important during the early stages of infection, for it can attach to and invade tissues of the hosts. Similarly to its flagellum, P. aeruginosa pili contribute greatly to its ability to adhere to mucosal surfaces and epithelial cells. Specifically, it is the pili’s tip that is responsible for the adherence to the host cell surface. P. aeruginosa have N-methyl-phenyl-alanine (NMePhe) or type IV pili . The pili are characterized as long polar filaments made up of homopolymers from the protein pilin, which is encoded by the pilA gene. Overall, P. aeruginosa flagellum and pili have similar functionality (for attachment) and structure (both are filamentous structures on the surface of the cell), and their motility is controlled by RpoN, especially during initial attachment to the human host and under low nutrient conditions.
         Pseudomonas aeruginosa Scanning Electron Micrograph. From the Centers for Disease Control and Prevention(CDC) When infecting its host, P. aeruginosa is starved for iron because iron deprivation of an infecting pathogen is the key part in the humans’ innate defense mechanism. To overcome this challenge, P. aeruginosa synthesizes two siderophores: pyochelin and pyoverdin. P. aeruginosa then secrets these sideophores to the exterior of the cell, where they bind tightly to iron and bring the iron back into the cell. Additionally, P. aeruginosa can also use iron from enterobactin, a special siderophore produced by E. coli for iron transport, to satisfy its iron need.
P. aeruginosa is a facultative aerobe; its preferred metabolism is respiration. It gains energy by transferring electrons from glucose, a reduced substrate, to oxygen, the final electron acceptor. The breakdown of glucose requires it to oxidize to gluconate in the periplasm, then it will be brought inside the inner membrane by a specific energy-dependent gluconate uptake system. Once inside, gluconate is phosphorylated to 6-P-gluconate, which will enter the central metabolism to produce energy for the cell. When P. aeruginosa is in anaerobic conditions, however, P. aeruginosa uses nitrate as a terminal electron acceptor. Under oxidative-stress conditions, P. aeruginosa synthesizes Fe- or Mn- containing superoxide dismutase (SOD) enzymes, which catalyze the very reactive O- to H2O2 and O2. It also detoxifies H2O2 to O2 and H2O by using catalase.
         Since P. aeruginosa can live in both inanimate and human environments, it has been characterized as a “ubiquitous” microorganism. This versatility is made possible by a large number of enzymes that allow P. aeruginosa to use a diversity of substances as nutrients. Most impressively, P. aeruginosa can switch from growing on nonmucoid to mucoid environments, which comes with a large synthesis of alginate. In inanimate environment, P. aeruginosa is usually detected in water-reservoirs polluted by animals and humans, such as sewage and sinks inside and outside of hospitals. It is also found in swimming pools and whirlpools because the warm temperatures are favorable to its growth. Because it thrived in warm conditions, however, it was determined to be the culprit of the Hot Tub Rash, in which direct contact between the skin and the infected water from the tub will make the infected skin itchy and turn it a bumpy red color . In addition, P. aeruginosa is an opportunistic human pathogen that causes chronic infections in patients with cystic fibrosis and is the leading cause of death by Gram-negative bacteria (more under pathology).
          Although most P. aeruginosa-plant interactions are detrimental to the plant, a recent study has found a P. aeruginosa strain that actually supports plant growth. This characteristic, along with the fact that P. aeruginosa can degrade polycyclic aromatic hydrocarbons, suggests the future uses of P. aeruginosa for environmental detoxification of synthetic chemicals and pesticides and for industrial purposes. Psuedomonas aeruginosa is unique due to its ability to infect both humans and plants, one of the few organisms that can infect both kingdoms.
         Five stages of Pseudomonas aeruginosa biofilm development. Courtesy of Peg Dirchx and David Davies. P. aeruginosa groups tend to form biofilms, which are complex bacterial communities that adhere to a variety of surfaces, including metals, plastics, medical implant materials, and tissue. Biofilms are characterized by “attached for survival” because once they are formed, they are very difficult to destroy. Depending on their locations, biofilms can either be beneficial and detrimental to the environment. For instance, the biofilms found on rocks and pebbles underwater of lakes and ponds are an important food source for many aquatic organisms. On the contrary, those that developed on the interiors of water pipes might cause clogging and corrosions.
       Pseudomonas aeruginosa colonial growth pattern on a blood agar plate. From the Center of Diseases Control and Prevention (CDC).P. aeruginosa rarely causes disease in healthy humans. It is usually linked with patients whose immune system is compromised by diseases or trauma. It gains access to these patients’ tissues through the burns, for the burn victims, or through an underlying disease, like cystic fibrosis. First, P. aeruginosa adheres to tissue surfaces using its flagellum, pili, and exo-S; then, it replicates to create infectious critical mass; and lastly, it makes tissue damage using its virulence factors. Since the powerful exotoxins and endotoxins released by P. aeruginosa during bacteremias continue to infect the host even after P. aeruginosa has been killed off by antibiotics, acute diseases caused by P. aeruginosa tend to be chronic and life-threatening. Furthermore, with the exception of the cystic fibrosis strain, most P. aeruginosa strains that attack compromised patients tend to be nonmucoid. And even though a small amount of patients infected by P. aeruginosa developed severe sepsis with lesions with black centers, most patients exhibited no obvious pathological effects of the colonization.
        Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians. With a mutation on chromosome 7, a CF lung cannot transport chloride (Cl-), sodium (Na+), and water from the basolateral to the secretory epithelia. This disruption in the salt and water balance in the cell results in the production of a thick mucus, which becomes the ideal home for potential pathogens. P. aeruginosa attacks CF patients via airway and once it is in, it uses its flagellum to go to the hypoxic zone, an oxygen-depleted environment. At this location, P. aeruginosa undergoes a transition from an aerobic to an anaerobic microbe and starts forming biofilms anaerobically. Once this is formed, the P. aeruginosa in this community can sense their population via quorum sensing, where they secret low molecular weight pheromones that enable them to communicate with each other (23). This gives them the ability to resist many defenses, including anti-Pseudomonas antibiotics such as ticarcillin, ceftazidime, tobramycin, and ciprofloxacin, because once the bacteria sense that their outer layer of biofilm is being destroyed, the inner layers will grow stronger to reestablish the community (24). P. aeruginosa is also resistant to many antibiotics and chemotherapeutic agents due to their intrinsic resistance. This is caused by the low permeability to antibiotics of the outer membrane and by the production of β-lactamases against multidrug efflux pumps and β-lactam antibiotics.
        P. aeruginosa communicates with other cells through quorum-sensing. This form of communication allows the cells to regulate gene production which results in control of certain cell functions. One of the enzymes responsible for quorum sensing is tyrosine phosphatase (TpbA). This enzyme relays extracellular quorum sensing signals to polysaccharide production and biofilm formation outside the cells. P. aeruginosa attaches to surfaces by way of biofilm production. Quorum-sensing can be a drug target to cure infections caused by P. aeruginosa. Quorum-quenching is used to blocks the signaling mechanism of quorum-sensing and prevents biofilm formation in P. aeruginosa. Yi-Hu Dong and his colleagues were able to prevent biofilm formation in mice under laboratory conditions.
        P. aeruginosa secrets many virulent factors to colonize the cells of its host. For example, exotoxin A, the most toxic protein produced by P. aeruginosa, catalyzes the ADP-ribosylation to form ADP-ribosyl-EF-2, which inhibits the protein synthesis of the host’s cells. Moreover, elastase, an extracellular zinc protease, attacks eukaryotic proteins such as collagen and elastin and destroys the structural proteins of the cell. It also breaks down human immunoglobin and serum alpha proteins.
Furthermore, P. aeruginosa infects animals. In an experiment, intravenous injection of virulent P. aeruginosa was injected into mice and these animals usually died within 24-48 hours. When a smaller dose was injected, characteristic signs of infection such as weight loss, focal lesions in liver, spleen, and kidneys, followed by death within 3-10 days, would take place. P. aeruginosa has also been found to cause outbreaks of pneumonia in guinea pigs, and although it also attacks plants, not a lot of research has been done in this area.
        Pseudomonas aeruginosa is an environmentally ubiquitous opportunistic pathogen. Epidermal infections often result from P. aeruginosa infiltrating through a human host’s first line of defenses, entering the body through the skin at the site of an open wound. P. aeruginosa is a common member of hospital bacterial communities where it can infect immunocompromised individuals including burn victims. P. aeruginosa is a source of bacteremia in burn victims [36]. Following severe skin damage, the prevalence of P. aeruginosa in the environment increases the probability of the organism accessing the bloodstream through the burn victim’s exposed deep epidermal tissue. Previous research of antibody-mediated host defenses indicates that on the fifth day after the initial burn, Fc receptor expression is reduced in polymorphonuclear leukocytes (PMNs). Without the Fc receptor, PMN chemotaxis is greatly reduced and the PMNs become less effective at preventing infection.
P. aeruginosa can be transmitted to a host via fomites, vectors, and hospital workers who are potential carriers for multiply-antibiotic-resistant strains of the pathogen. Furthermore, any P. aeruginosa already present on a burn victim’s skin before the injury can transform from an innocuous organism on the surface of the skin to a source of infection in the bloodstream and body tissues of the same individual.
        The pili and flagella of P. aeruginosa play a vital role in the infection of burns and wounds [36]. Controlled infection of burn wounds on animal and plant models with P. aeruginosa strains devoid of pili and flagella demonstrate a trend of decreased virulence. Without these morphological virulence factors, the bacteria exhibit a substantially decreased survival rate at the wound site and a decreased ability to disseminate within the host organism. The spread of P. aeruginosa within host organisms is also dependent on the microorganism’s elastase production and other protease mechanisms. Bacterial elastase and other bacterial proteases degrade the host’s proteins, including the structural proteins within membranes, disrupting the host’s physical barriers against the spread of infection. Elastase also assists P. aeruginosa in avoiding phagocytotic antibody-mediated cytotoxicity at the site of the wound by inhibiting monocyte chemotaxis.
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