There are other control elements that affect the quorumsensing regulatory circuit. The gacA gene product is a transcriptional activator that among other things induces C4-HSL production (44). The rsaL gene is downstream of the lasR gene and it is involved in negatively regulating lasR (45). Vfr is a global regulator that affects a mild activation of lasR (46). The environmental signals that these regulators respond to are unknown. Furthermore, the physiological significance of the observed levels of regulation by these factors remains to be determined. Further complicating the quorum-sensing regulatory scheme is the recent discovery that a specific quinolone produced by P. aeruginosa can serve as an extracellular signal to activate lasB (8). The mechanisms that underlie quinolone signaling remain unknown.

Mutations in elements of the quorum-sensing machinery in P. aeruginosa do not markedly influence the growth of this bacterium in the laboratory. For example, the growth rate of the LasI⁻, RhlI⁻ double mutant PAO-MW1 in Luria–Bertani broth at 30°C or 37°C is similar to that of the wild-type PAO1 under normal laboratory culture conditions. Yet quorum-sensing mutant strains show severe virulence defects in various mouse models, in invertebrate models, and in a plant model system. We will briefly describe the results of experiments in which colonization of the lungs in a neonatal mouse model by a LasR mutant was compared with colonization by the wild-type parental strain (23). When neonatal BALB/cByJ mice were inoculated intranasally with wild-type P. aeruginosa, the bacteria colonized the lung, causing an acute pneumonia, bacteremia, and death. In contrast, a LasR mutant strain could colonize the lung, but it did not achieve high densities and it did not cause pneumonia, bacteremia, or death. The mutant did not have a growth defect under laboratory conditions, it could invade the lung and survive but it could not cause disease.

Bacteria often tend to attach to surfaces and form communities enmeshed in a self-produced polymeric matrix. These communities are called a biofilm (2, 47). P. aeruginosa is often found in naturally occurring biofilms. Under the appropriate laboratory conditions, P. aeruginosa forms characteristic biofilms that can be several hundred micrometers thick (Fig. 3). Development of a mature biofilm proceeds through a programmed series of events (for a recent review see ref.2). After attachment, cells multiply to form a layer on a solid surface. Individuals in the layer then exhibit a surface motility called twitching. Twitching depends on type IV pili. As a result of twitching motility, small groups of P. aeruginosa called microcolonies form. Microcolonies then differentiate to form a mature biofilm. Microcolonies in a mature biofilm have tower- and mushroom-shaped architectures. The cells in these structures are encased in an extracellular polysaccharide matrix. Water channels that allow the flow of nutrients into and waste products out of the biofilm innervate these structures. There is a significant physiological heterogeneity within biofilms. In P. aeruginosa biofilms there is a steep oxygen gradient. Oxygen is present at measurable concentrations mainly at the periphery of the biofilm. Oxygen microelectrode studies have also shown that water channels serve to bring oxygen to deeper areas of the biofilm. Similar gradients may be expected for pH and nutrients. These gradients dictate physiological variability among individual cells in the biofilm, with slower-growing cells present deeper within the biofilm and more actively growing cells at the periphery. This heterogeneity in physiological activity makes studying biofilms

Front Matter (R1-R5)

Pathogens and Host: The Dance is the Same, the Couples are Different (1-2)

Striking a Balance: Modulation of the Actin Cytoskeleton by Salmonella (3-10)

Structure and Function of Pectic Enzymes: Virulence Factors of Plant Pathogens (11-18)

Pseudomonas syringae Hrp Type III Secretion System and Effector Proteins (19-26)

Molecular and Cell Biology Aspects of Plague (27-32)

A Framework for Interpreting the Leucine-rich Repeats of the Listeria Internalins (33-37)

Acyl-homoserine Lactone Quorum Sensing in Gram-negative Bacteria: A Signaling Mechanism Involved in Associations with Higher Organisms (38-42)

Phenotypic Variation and Intracellular Parasitism by Histoplasma capsulatum (43-47)

Exploitation of Host Cells by Enteropathogenic Escherichia coli (48-55)

Genetic Complexity of Pathogen Perception by Plants: The Example of Rcr3, a Tomato Gene Required Specifically by Cf-2 (56-63)

Plants and Animals Share Functionally Common Bacterial Virulence Factors (64-70)

Role of the Cystic Fibrosis Transmembrane Conductance Regulator in Innate Immunity to Pseudomonas aeruginosa Infections (71-77)

Bad Bugs and Beleaguered Bladders: Interplay Between Uropathogenic Escherichia coli and Innate Host Defenses (78-84)

AvrPto-dependent Pto-interacting Proteins and AvrPto-interacting Proteins in Tomato (85-89)

Reactive Oxygen and Nitrogen Intermediates in the Relationship Between Mammalian Hosts and Microbial Pathogens (90-97)

Nitric Oxide and Salicylic Acid Signaling in Plant Defense (98-104)

The Role of Antimicrobial Peptides in Animal Defenses (105-110)

Suramin Inhibits Initiation of Defense Signaling by Systemin, Chitosan, and a ß-glucan Elicitor in Suspension-cultured Lycopersicon Peruvianum Cells (111-116)