Chapter 5 : Relationships Between Community Behavior and Pathogenesis in

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can be isolated from soil, water, and the skin of healthy human beings. One of the many goals of this research has been to understand the key factors that allow to make this transition, in order to both combat and prevent infections. Much of this research has involved careful genetic and biochemical characterizations of the virulence factor in question. This chapter reviews some of virulence factors and the roles they are thought to play in pathogenesis. It is known that utilizes acyl-HSL quorum sensing to regulate virulence gene expression. The chapter reviews quorum sensing in this organism with an emphasis on quorum sensing-signal generation. In , quorum sensing has been shown to be involved in coordinating the community behavior required for the formation of these structures. The chapter addresses the role of biofilm formation in pathogenesis and its relationship to quorum sensing. The same study suggested that LasA protease might be vital for pathogenesis. Pyocyanin has also been implicated in impairing host defense mechanisms in chronic infection of the CF lung; however, the actual role pyocyanin plays in pathogenesis remains uncertain. is a formidable opportunistic human pathogen that possesses an arsenal of virulence factors. These factors are important for different aspects of pathogenesis, such as colonization and cytotoxicity.

Citation: Parsek M, Greenberg E. 2000. Relationships Between Community Behavior and Pathogenesis in , p 77-92. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch5
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Image of FIGURE 1

A model of the quorum-sensing regulatory network in . This diagram illustrates the components of the and quorum-sensing systems. Each system has its own autoinducer synthase (LasI and RhlI), transcriptional regulator (LasR and RhlR), and acyl-HSL (3-oxo-dodecanoyl-HSL and butyryl-HSL). The system regulates the system, which in turn regulates , a sigma factor of stationary phase genes. The clear, black, and stippled boxes indicate genes thought regulated by the , , and both systems.

Citation: Parsek M, Greenberg E. 2000. Relationships Between Community Behavior and Pathogenesis in , p 77-92. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch5
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Image of FIGURE 2

Acyl-HSL biosynthesis by RhlI. The substrates for butyryl-HSL synthesis are SAM and butyryl-ACP. The first step in acyl-HSL synthesis is the binding of SAM to RhlI, which is followed by binding of butyryl-ACP. Amide bond formation occurs between SAM and the acyl group of butyryl- ACP, accompanied by the release of ACP. The next step is lactonization of the homoserine lactone ring and subsequent release of butyryl-HSL and finally 5′-methylthioadenosine. A number of SAM analogs have been identified as inhibitors of this reaction. Reprinted from reference 88 with permission. Copyright 1999 National Academy of Sciences, U.S.A.

Citation: Parsek M, Greenberg E. 2000. Relationships Between Community Behavior and Pathogenesis in , p 77-92. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch5
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Image of FIGURE 3

Epifluorescence and scanning confocal photomicrographs of wild-type and a quorum-sensing mutant. The top three panels represent epifluorescence micrographs of the wild-type PAO1, a mutant, and a mutant complemented with exogenously added autoinducer (3-oxododecanoyl-HSL) as indicated. The bottom three panels represent saggital or side views of the biofilms generated with SCLM. The attachment surface is the axis. The bacteria are tagged with the green fluorescent protein. The mutant biofilm is thinner and more densely packed than the wild-type biofilm. Addition of autoinducer to the growth medium complements the mutant phenotype and restores a wild-type biofilm phenotype. Reprinted with permission from reference 22. Copyright 1998 American Association for the Advancement of Science.

Citation: Parsek M, Greenberg E. 2000. Relationships Between Community Behavior and Pathogenesis in , p 77-92. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch5
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