Polynucleotide Phosphorylase Regulates Multiple Virulence Factors and the Stabilities of Small RNAs RsmY/Z in Pseudomonas aeruginosa

Various gram-negative animal and plant pathogens use a novel, sec-independent protein secretion system as a basic virulence mechanism. It is becoming increasingly clear that these so-called type III secretion systems inject (translocate) proteins into the cytosol of eukaryotic cells, where the translocated proteins facilitate bacterial pathogenesis by specifically interfering with host cell signal transduction and other cellular processes. Accordingly, some type III secretion systems are activated by bacterial contact with host cell surfaces. Individual type III secretion systems direct the secretion and translocation of a variety of unrelated proteins, which account for species-specific pathogenesis phenotypes. In contrast to the secreted virulence factors, most of the 15 to 20 membrane-associated proteins which constitute the type III secretion apparatus are conserved among different pathogens. Most of the inner membrane components of the type III secretion apparatus show additional homologies to flagellar biosynthetic proteins, while a conserved outer membrane factor is similar to secretins from type II and other secretion pathways. Structurally conserved chaperones which specifically bind to individual secreted proteins play an important role in type III protein secretion, apparently by preventing premature interactions of the secreted factors with other proteins. The genes encoding type III secretion systems are clustered, and various pieces of evidence suggest that these systems have been acquired by horizontal genetic transfer during evolution. Expression of type III secretion systems is coordinately regulated in response to host environmental stimuli by networks of transcription factors. This review comprises a comparison of the structure, function, regulation, and impact on host cells of the type III secretion systems in the animal pathogens Yersinia spp., Pseudomonas aeruginosa, Shigella flexneri, Salmonella typhimurium, enteropathogenic Escherichia coli, and Chlamydia spp. and the plant pathogens Pseudomonas syringae, Erwinia spp., Ralstonia solanacearum, Xanthomonas campestris, and Rhizobium spp. Show more

Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enyzmes by the outer membrane. Here we show that the type VI secretion system (T6SS) of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyze peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa utilizes specific periplasmically-localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active T6SS, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit. Show more

Pseudomonas aeruginosa is an important pathogen causing a wide range of acute and chronic infections. P. aeruginosa rarely causes infection in the normal host, but is an efficient opportunistic pathogen causing serious infections in patients who are mechanically ventilated, individuals who are immunocompromised, and patients with malignancies or HIV infection. Among these risk groups, the most vulnerable hosts are neutropenic and patients who are mechanically ventilated. In addition, P. aeruginosa is the most prevalent chronic infection contributing to the pathogenesis of cystic fibrosis. Because of the ubiquitous nature of P. aeruginosa and its ability to develop resistance to antibiotics, it continues to be problematic from a treatment perspective. The pathogenicity of P. aeruginosa is largely caused by multiple bacterial virulence factors and genetic flexibility enabling it to survive in varied environments. Lung injury associated with P. aeruginosa infection results from both the direct destructive effects of the organism on the lung parenchyma and exuberant host immune responses. This article focuses on the major bacterial virulence factors and important aspects of the host immunity that are involved in the pathogenesis of serious P. aeruginosa infection. In addition to antibiotic therapy, strategies directed toward enhancing host defense and/or limiting excessive inflammation could be important to improve outcome in P. aeruginosa lung infections. Show more