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Identified Virulence Factors of Pseudomonas : Adherence


Flagella
Related genes: fleN; fleQ; fleR; flgC; flgD; flgE; flgF; flgG; flgH; flgI; flgJ; flgK; flgL; flhA; flhB; flhF; fliC; fliD; fliE; fliF; fliG; fliH; fliI; fliJ; fliM; fliN; fliO; fliP; fliQ; fliR;
Keywords: Adherence; Motility;
Functions:
Swimming motility
Play a role in biofilm formation and other pathogenic adaptations
References:
Feldman M, et al., 1998. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect. Immun. 66(1):43-51.
O'Toole GA, Kolter R, 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30(2):295-304.
Ciacci-Woolwine F, et al., 1999. Induction of cytokine synthesis by flagella from gram-negative bacteria may be dependent on the activation or differentiation state of human monocytes. Infect. Immun. 67(10):5176-5185.
Adamo R, et al., 2004. Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and toll-like receptor 2 as well as toll-like receptor 5. Am J. Respir. Cell Mol. Biol. 30(5):627-634.
Dasgupta N, et al., 2003. A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol. Microbiol. 50(3):809-824.


LPS
Related genes: waaA; waaC; waaF; waaG; waaP; wzy; wzz;
Keywords: Adherence; Endotoxin;
Characteristics:
Two distinct forms of LPS: A-band and B-band. A-band is a homopolymer of α-linked D-rhamnose, whereas B-band LPS is a heteropolymer
Functions:
Mediates biological effects including resistance to serum killing and phagocytosis
The binding to normal CFTR (cystic fibrosis transmembrane conductance regulator) and invasion of host cells may make a contribution to virulence in the human eye
Internalization by binding to normal CFTR protein expressed by airway epithelial cells followed by desquamation of bacteria-laden epithelial cells, constitutes a host defense mechanism. If this mechanism fails to function properly, abnormally high bacterial carriage would promote the establishment of chronic bacterial infection
Mechanism:
Binding interaction occurs between the first extracellular loop of CFTR (predicted to be in amino acids 108-117 of the mature protein) and the complete outer portion of the core polysaccharide of the LPS
References:
Rocchetta HL, et al., 1999. Genetics of O-antigen biosynthesis in Pseudomonas aeruginosa. Microbiol. Mol. Biol. Rev. 63(3):523-553.
Lyczak JB, et al., 2000. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect. 2(9):1051-1060.
Schroeder TH, et al., 2002. CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-κ B translocation. Proc. Natl. Acad. Sci. USA. 99(10):6907-6912.


Type IV pili
Related genes: chpA; chpB; chpC; chpD; chpE; fimT; fimU; fimV; pilA; pilB; pilC; pilD; pilE; pilF; pilG; pilH; pilI; pilJ; pilK; pilM; pilN; pilO; pilP; pilQ; pilR; pilS; pilT; pilU; pilV; pilW; pilX; pilY1; pilY2;
Keywords: Adherence; twitching motility;
Characteristics:
pilA, B, C, D, E, F, M, N, O, P, Q, T, U, V, W, X, Y1, Y2, Z, and fimT, U. V are involved in the biogenesis and machanical function of pili, pilG, H, I, K, chpA, B, C, D, E, pilS, R, fimS, rpoN, algR, algU, and vfr are involved in transcriptional regulation and chemosensory pathways that control the expression or activity of the twitching motility of the pili
Functions:
Attaches to host cells, but not to mucin, causing a twitching motility that allows the bacteria to move along the cell surface
biofilm formation
Mechanism:
The C-terminal receptor-binding domain of pilin binds to asialoGM1 gangliosies on host cells. Generally, GM1 gangliosides contain a sialic acid moiety. P.aeruginosa produces a neuraminidase which removes sialic acid residues from the GM1 to form the asialoGM1, which is a better receptor for the pili
The asialoGM1 is present in increased abundance on the surface of cystic fibrosis respiratory epithelial cells
References:
Hahn HP, 1997. The type-4 pilus is the major virulence-associated adhesin of Pseudomonas aeruginosa--a review. Gene 192(1):99-108.
O'Toole GA, Kolter R, 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30(2):295-304.
Comolli JC, et al., 1999. Pili binding to asialo-GM1 on epithelial cells can mediate cytotoxicity or bacterial internalization by Pseudomonas aeruginosa. Infect. Immun. 67(7):3207-3214.
Keizer DW, et al., 2001. Structure of a pilin monomer from Pseudomonas aeruginosa: implications for the assembly of pili. J. Biol. Chem. 276(26):24186-24193.
Skerker JM, Berg HC, 2001. Direct observation of extension and retraction of type IV pili. Proc. Natl. Acad. Sci. USA. 98(12):6901-6904.
Mattick JS, 2002. Type IV pili and twitching motility. Annu. Rev. Microbiol. 56:289-314.
Whitchurch CB, et al., 2004. Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa. Mol. Microbiol. 52(3):873-893.






Terms
biofilm
Formed by bacteria attached to surfaces, which upon their aggregation release extracellular polysaccharides that form a polymeric matrix or glycocalyx. Biofilms are architecturally complex structures made up of microcolonies and characteristic mushroom or pillar-like arrangements that are separated by channels that permit the circulation of water and nutrients. Medically important biofilms, which can be found on catheters, artificial joints and stints for example, are extremely difficult to eradicate, because they are shielded from host defenses such as phagocytosis or antibodies and are resistant to antibiotics. In addition, biofilms can be the source of chronic infections, since they continuously shed planktonic bacteria that can multiply.
The formation of a biofilm occurs in three stages: initial attachment, proliferation resulting in the formation of microcolonies, and differentiation of the microcolonies into distinct structures
twitching motility
It is a flagella-independent form of bacterial translocation over moist surfaces. It occurs by extension, tethering, and then retraction of polar type IV pili, which operate in a manner similar to a grapping hook. Twitching motility is important in host colonization and formation of biofilms.







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