Phagocytosis of<unk>  by neutrophil in<unk> tient with bloodstream infection (Gram stain) An opportunistic, nosocomial<unk> thogen of immunocompromised individuals,<unk>  typically infects the airway, urinary tract, burns, and wounds, and also causes other blood infections. + Infections Details and common associations High-risk groups Pneumonia Diffuse bronchopneumonia Cystic fibrosis, non-CF bronchiectasis<unk> tients Septic shock Associated with a purple-black skin lesion ecthyma gangrenosum Neutropenic<unk> tients Urinary tract infection Urinary tract catheterization Gastrointestinal infection Necrotising enterocolitis Premature infants and neutropenic cancer<unk> tients Skin and soft tissue infections Hemorrhage and necrosis People with burns or wound infections It is the most common cause of infections of burn injuries and of the outer ear (otitis externa), and is the most frequent colonizer of medical devices (e.g., catheters).<unk>  can be spread by equipment that gets contaminated and is not properly cleaned or on the hands of healthcare workers.<unk>  can, in rare circumstances, cause community-acquired pneumonias, as well as ventilator-associated pneumonias, being one of the most common agents isolated in several studies. Pyocyanin is a virulence factor of the bacteria and has been known to cause death in C. elegans by oxidative stress. However, salicylic acid can inhibit pyocyanin production. One in ten hospital-acquired infections is from<unk> . Cystic fibrosis<unk> tients are also predisposed to<unk>  infection of the lungs due to a functional loss in chloride ion movement across cell membranes as a result of a mutation.<unk>  may also be a common cause of "hot-tub rash" (dermatitis), caused by lack of proper, periodic attention to water quality. Since these bacteria thrive in moist environments, such as hot tubs and swimming pools, they can cause skin rash or swimmer's ear.<unk>  is also a common cause of postoperative infection in radial keratotomy surgery<unk> tients. The organism is also associated with the skin lesion ecthyma gangrenosum.<unk>  is frequently associated with osteomyelitis involving puncture wounds of the foot, believed to result from direct inoculation with<unk>  via the foam<unk> dding found in tennis shoes, with diabetic<unk> tients at a higher risk. A comparative genomic analysis of 494 compete<unk>  genomes, including 189 complete<unk>  genomes, identified several proteins that are shared by the vast majority of<unk>  strains, but are not observed in other analyzed<unk>  genomes. Intrigungly, these<unk> -specific core proteins, such as CntL, CntM, PlcB, Acp1, MucE, SrfA, Tse1, Tsi2, Tse3, and EsrC are known to play an important role in this species'<unk> thogenicity. Toxins<unk>  uses the virulence factor exotoxin A to inactivate eukaryotic elongation factor 2 via ADP-ribosylation in the host cell, much as the diphtheria toxin does. Without elongation factor 2, eukaryotic cells cannot synthesize proteins and necrotise. The release of intracellular contents induces an immunologic response in immunocompetent<unk> tients. In addition<unk>  uses an exoenzyme, ExoU, which degrades the plasma membrane of eukaryotic cells, leading to lysis. Increasingly, it is becoming recognized that the iron-acquiring siderophore, pyoverdine, also functions as a toxin by removing iron from mitochondria, inflicting damage on this organelle. Phenazines Phenazines are redox-active pigments produced by<unk> . These pigments are involved in quorum sensing, virulence, and iron acquisition.<unk>  produces several pigments all produced by a biosynthetic<unk> thway: pyocyanin, 1-hydroxyphenazine, phenazine-1-carboxamide, 5-methylphenazine-1-carboxylic acid betaine, and<unk> n A. Two operons are involved in phenazine biosynthesis: phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2. These operons convert a chorismic acid to the phenazines mentioned above. Three key genes, phzH, phzM, and phzS convert phenazine-1-carboxylic acid to the phenazines mentioned above. Though phenazine biosynthesis is well studied, questions remain as to the final structure of the brown phenazine pyomelanin. When pyocyanin biosynthesis is inhibited, a decrease in<unk> <unk> thogenicity is observed in vitro. This suggests that pyocyanin is most responsible for the initial colonization of<unk>  in vivo. Triggers With low phosphate levels,<unk>  has been found to activate from benign symbiont to express lethal toxins inside the intestinal tract and severely damage or kill the host, which can be mitigated by providing excess phosphate instead of antibiotics. Plants and invertebrates In higher plants,<unk>  induces soft rot, for example in Arabidopsis thaliana (Thale cress) and Lactuca sativa (lettuce). It is also<unk> thogenic to invertebrate animals, including the nematode Caenorhabditis elegans, the fruit fly Drosophila and the moth Galleria mellonella. The associations of virulence factors are the same for plant and animal infections. In both insects and plants, Rumbaugh et al. 1999 (b) finds<unk>  virulence to be highly quorum sensing dependent. Its QS is in turn highly dependent upon such genes as acyl-homoserine-lactone synthase, lasI, and rhlI. Quorum sensing<unk>  is an opportunistic<unk> thogen with the ability to coordinate gene expression in order to compete against other species for nutrients or colonization. Regulation of gene expression can occur through cell-cell communication or quorum sensing (QS) via the production of small molecules called autoinducers that are released into the external environment. These signals, when reaching specific concentrations correlated with specific population cell densities, activate their respective regulators thus altering gene expression and coordinating behavior.<unk>  employs five interconnected QS systems – las, rhl, pqs, iqs and pch – that each produce unique signaling molecules. las and rhl systems are responsible for the activation of numerous QS-controlled genes, pqs system is involved in quinolone signaling and iqs system plays an important role in intercellular communication. QS in<unk>  is organized in a hierarchical manner. At the top of the signaling hierarchy is the las system, since las regulator initiate the QS regulatory system by activating the transcription of a number of other regulators, such as rhl. So, the las system defines a hierarchical QS cascade from the las to the rhl regulons. Detection of these molecules indicates<unk>  is growing as biofilm within the lungs of cystic fibrosis<unk> tients. The impact of QS and especially las systems on the<unk> thogenicity of<unk>  is unclear, however. Studies have shown that lasR-deficient mutants are associated with more severe outcomes in cystic fibrosis<unk> tients and are found in up to 63% of chronically infected cystic fibrosis<unk> tients despite impaired QS activity. QS is known to control expression of a number of virulence factors in a hierarchical manner, including the pigment pyocyanin. However, although las system initiates the regulation of the gene expression, its absence does not lead to loss of the virulence factors. Recently, it has been demonstrated that rhl system<unk> rtially controls las-specific factors, such as proteolytic enzymes responsible for elastolytic and staphylolytic activities, but in a delayed manner. So, las is a direct and indirect regulator of QS-controlled genes. Another form of gene regulation that allows the bacteria to rapidly adapt to surrounding changes is through environmental signaling. Recent studies have discovered anaerobiosis can significantly impact the major regulatory circuit of QS. This important link between QS and anaerobiosis has a significant impact on production of virulence factors of this organism. Garlic experimentally blocks quorum sensing in<unk> . Biofilms formation and cyclic di-GMP As in most Gram negative bacteria,<unk>  biofilm formation is regulated by one single molecule: cyclic di-GMP. At low cyclic di-GMP concentration,<unk>  has a free-swimming mode of life. But when cyclic di-GMP levels increase,<unk>  start to establish sessile communities on surfaces. The intracellular concentration of cyclic di-GMP increases within seconds when<unk>  touches a surface (e.g.: a rock, plastic, host tissues...). This activates the production of adhesive pili, that serve as "anchors" to stabilize the attachment of<unk>  on the surface. At later stages, bacteria will start attaching irreversibly by producing a strongly adhesive matrix. At the same time, cyclic di-GMP represses the synthesis of the flagellar machinery, preventing<unk>  from swimming. When suppressed, the biofilms are less adherent and easier to treat. The biofilm matrix of<unk>  is composed of nucleic acids, amino acids, carbohydrates, and various ions. It mechanically and chemically protects<unk>  from aggression by the immune system and some toxic compounds.<unk>  biofilm's matrix is composed of 2 types of sugars (or "exopolysacharides") named PSL and PEL: * Polysaccharide synthesis locus (PSL) and cyclic di-GMP form a positive feedback loop. PSL stimulates cyclic di-GMP production, while high cyclic di-GMP turns on the operon and increases activity of the operon. This 15-gene operon is responsible for the cell-cell and cell-surface interactions required for cell communication. It is also responsible for the sequestering of the extracellular polymeric substance matrix. * PEL is a cationic exopolysaccharide that cross-links extracellular DNA in the<unk>  biofilm matrix. Upon certain cues or stresses,<unk>  revert the biofilm program and detach. Recent studies have shown that the dispersed cells from<unk>  biofilms have lower cyclic di-GMP levels and different physiologies from those of planktonic and biofilm cells. Such dispersed cells are found to be highly virulent against macrophages and C. elegans, but highly sensitive towards iron stress, as compared with planktonic cells. Biofilms and treatment resistance Biofilms of<unk>  can cause chronic opportunistic infections, which are a serious
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Pasteurella