<i>Pseudomonas aeruginosa</i>protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions

Malloy, Jaret; Veldhuizen, Ruud A. W.; Thibodeaux, Brett A.; O’Callaghan, Richard J.; Wright, Jo Rae

doi:10.1152/ajplung.00322.2004

Cited by 106 publications

(89 citation statements)

References 40 publications

(54 reference statements)

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“…PIAAMV activated the expression of the Xcp type II secretion apparatus genes (95) (see Table S1 in the supplemental material) as well as protease IV (piv). Protease IV degrades surfactant proteins and is important in eye infections but may also contribute to acute lung infection (96). Interestingly, triclosan alone does not increase the gene expression level of either the T6SS or T2SS (86).…”

Section: Figmentioning

confidence: 98%

Genes Required for and Effects of Alginate Overproduction Induced by Growth of Pseudomonas aeruginosa on Pseudomonas Isolation Agar Supplemented with Ammonium Metavanadate

Damron¹,

Barbier²,

McKenney³

et al. 2013

Journal of Bacteriology

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cPseudomonas aeruginosa is an opportunistic pathogen that can adapt to changing environments and can secrete an exopolysaccharide known as alginate as a protection response, resulting in a colony morphology and phenotype referred to as mucoid. However, how P. aeruginosa senses its environment and activates alginate overproduction is not fully understood. Previously, we showed that Pseudomonas isolation agar supplemented with ammonium metavanadate (PIAAMV) induces P. aeruginosa to overproduce alginate. Vanadate is a phosphate mimic and causes protein misfolding by disruption of disulfide bonds. Here we used PIAAMV to characterize the pathways involved in inducible alginate production and tested the global effects of P. aeruginosa growth on PIAAMV by a mutant library screen, by transcriptomics, and in a murine acute virulence model. The PA14 nonredundant mutant library was screened on PIAAMV to identify new genes that are required for the inducible alginate stress response. A functionally diverse set of genes encoding products involved in cell envelope biogenesis, peptidoglycan remodeling, uptake of phosphate and iron, phenazine biosynthesis, and other processes were identified as positive regulators of the mucoid phenotype on PIAAMV. Transcriptome analysis of P. aeruginosa cultures growing in the presence of vanadate showed differential expression of genes involved in virulence, envelope biogenesis, and cell stress pathways. In this study, it was observed that growth on PIAAMV attenuates P. aeruginosa in a mouse pneumonia model. Induction of alginate overproduction occurs as a stress response to protect P. aeruginosa, but it may be possible to modulate and inhibit these pathways based on the new genes identified in this study.

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Section: Figmentioning

confidence: 98%

Genes Required for and Effects of Alginate Overproduction Induced by Growth of Pseudomonas aeruginosa on Pseudomonas Isolation Agar Supplemented with Ammonium Metavanadate

Damron¹,

Barbier²,

McKenney³

et al. 2013

Journal of Bacteriology

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“…95 Similarly, a protease of Aspergillus fumigatus cleaves several complement proteins and thereby prevents complement activation, 14 while protease IV of P. aeruginosa degrades surfactant proteins. 122 Several Gram-positive pathogens alter the acetylation patterns of peptidoglycan in their cell wall, as a mechanism to resist degradation by lysozyme. 43 The bacterial capsule is important in evading complement 80 but also confers resistance to cathelicidins among some pathogens, including N. meningitidis.…”

Section: Effects Of Predisposing Factors On the Function Of Innate Dementioning

confidence: 99%

Failure of Respiratory Defenses in the Pathogenesis of Bacterial Pneumonia of Cattle

Caswell

2013

Vet Pathol

104

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The respiratory system is well defended against inhaled bacteria by a dynamic system of interacting layers, including mucociliary clearance, host defense factors including antimicrobial peptides in the epithelial lining fluid, proinflammatory responses of the respiratory epithelium, resident alveolar macrophages, and recruited neutrophils and monocytes. Nevertheless, these manifold defenses are susceptible to failure as a result of stress, glucocorticoids, viral infections, abrupt exposure to cold air, and poor air quality. When some of these defenses fail, the lung can be colonized by bacterial pathogens that are equipped to evade the remaining defenses, resulting in the development of pneumonia. This review considers the mechanisms by which these predisposing factors compromise the defenses of the lung, with a focus on the development of bacterial pneumonia in cattle and supplemented with advances based on mouse models and the study of human disease. Deepening our understanding of how the respiratory defenses fail is expected to lead to interventions that restore these dynamic immune responses and prevent disease.

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“…Protease IV also degrades surfactant proteins A, B, and D, which are important for surface tension and innate immunity (35). The phospholipases PlcB, PlcH, and PlcN target the mucus layer and cell membrane, facilitating bacterial transit through the mucus layer and liberating nutrients exploited by the bacteria (36)(37)(38).…”

Section: Infection Maintenancementioning

confidence: 99%

Pouring Salt on a Wound: Pseudomonas aeruginosa Virulence Factors Alter Na+ and Cl- Flux in the Lung

Ballok

O’Toole

2013

Journal of Bacteriology

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Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen with multiple niches in the human body, including the lung. P. aeruginosa infections are particularly damaging or fatal for patients with ventilator-associated pneumonia, chronic obstructive pulmonary disease, and cystic fibrosis (CF). To establish an infection, P. aeruginosa relies on a suite of virulence factors, including lipopolysaccharide, phospholipases, exoproteases, phenazines, outer membrane vesicles, type III secreted effectors, flagella, and pili. These factors not only damage the epithelial cell lining but also induce changes in cell physiology and function such as cell shape, membrane permeability, and protein synthesis. While such virulence factors are important in initial infection, many become dysregulated or nonfunctional during the course of chronic infection. Recent work on the virulence factors alkaline protease (AprA) and CF transmembrane conductance regulator inhibitory factor (Cif) show that P. aeruginosa also perturbs epithelial ion transport and osmosis, which may be important for the long-term survival of this microbe in the lung. Here we discuss the literature regarding host physiology-altering virulence factors with a focus on Cif and AprA and their potential roles in chronic infection and immune evasion.

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Pseudomonas aeruginosaprotease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions

Cited by 106 publications

References 40 publications

Genes Required for and Effects of Alginate Overproduction Induced by Growth of Pseudomonas aeruginosa on Pseudomonas Isolation Agar Supplemented with Ammonium Metavanadate

Genes Required for and Effects of Alginate Overproduction Induced by Growth of Pseudomonas aeruginosa on Pseudomonas Isolation Agar Supplemented with Ammonium Metavanadate

Failure of Respiratory Defenses in the Pathogenesis of Bacterial Pneumonia of Cattle

Pouring Salt on a Wound: Pseudomonas aeruginosa Virulence Factors Alter Na+ and Cl- Flux in the Lung

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