Pseudomonas aeruginosa renews its virulence factors

Huber, Philippe; Basso, Pauline; Reboud, Emeline; Attrée, Ina

doi:10.1111/1758-2229.12443

Cited by 55 publications

(57 citation statements)

References 49 publications

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“…aeruginosa ’s ability to trigger NET release at various phases of growth as P . aeruginosa expresses different phenotypic features depending on its growth phase [46]. Early exponential phase cultures are characterized by motility and expression of virulence factors, while in later growth phases these features are lost and quorum-sensing molecules and extracellular polysaccharides become expressed to a greater extent [47].…”

Section: Resultsmentioning

confidence: 99%

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

et al. 2016

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Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections often characterized by robust neutrophilic infiltration. Neutrophils provide the first line of defense against P. aeruginosa. Aside from their defense conferred by phagocytic activity, neutrophils also release neutrophil extracellular traps (NETs) to immobilize bacteria. Although NET formation is an important antimicrobial process, the details of its mechanism are largely unknown. The identity of the main components of P. aeruginosa responsible for triggering NET formation is unclear. In this study, our focus was to identify the main bacterial factors mediating NET formation and to gain insight into the underlying mechanism. We found that P. aeruginosa in its exponential growth phase promoted strong NET formation in human neutrophils while its NET-inducing ability dramatically decreased at later stages of bacterial growth. We identified the flagellum as the primary component of P. aeruginosa responsible for inducing NET extrusion as flagellum-deficient bacteria remained seriously impaired in triggering NET formation. Purified P. aeruginosa flagellin, the monomeric component of the flagellum, does not stimulate NET formation in human neutrophils. P. aeruginosa-induced NET formation is independent of the flagellum-sensing receptors TLR5 and NLRC4 in both human and mouse neutrophils. Interestingly, we found that flagellar motility, not flagellum binding to neutrophils per se, mediates NET release induced by flagellated bacteria. Immotile, flagellar motor-deficient bacterial strains producing paralyzed flagella did not induce NET formation. Forced contact between immotile P. aeruginosa and neutrophils restored their NET-inducing ability. Both the motAB and motCD genetic loci encoding flagellar motor genes contribute to maximal NET release; however the motCD genes play a more important role. Phagocytosis of P. aeruginosa and superoxide production by neutrophils were also largely dependent upon a functional flagellum. Taken together, the flagellum is herein presented for the first time as the main organelle of planktonic bacteria responsible for mediating NET release. Furthermore, flagellar motility, rather than binding of the flagellum to flagellum-sensing receptors on host cells, is required for P. aeruginosa to induce NET release.

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Section: Resultsmentioning

confidence: 99%

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

et al. 2016

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“…P. aeruginosa can be especially virulent pathogens, expressing potent toxins, both proteases and the more complex TTSS that target specific eukaryotic receptors [37]. They express multiple PAMPs associated with the activation of inflammasomes (Fig.…”

Section: Resistance To Inflammasome-mediated Clearancementioning

confidence: 99%

Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

Riquelme¹,

Ahn²,

Prince³

2018

J Innate Immun

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Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.

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“…One of these contains strains previously referred to as “clonal outliers” (5–7); the first identified member of this group is strain PA7 (8). Although the virulence of P. aeruginosa is multifactorial, the two clades differ mainly in the way that they exert their cytolytic activity on human cells (6, 9, 10). The genomes of the PAO1/PA14 group contain the determinants of a well-studied export nanomachine called the type III secretion system (T3SS) that allows the injection of four main P. aeruginosa effectors harboring enzymatic activities (ExoS, ExoT, ExoY, and ExoU) directly into the host cell cytoplasm (reviewed in reference 11).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa Pore-Forming Exolysin and Type IV Pili Cooperate To Induce Host Cell Lysis

Basso

Ragno

Elsen

et al. 2017

mBio

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113

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Clinical strains of Pseudomonas aeruginosa lacking the type III secretion system genes employ a toxin, exolysin (ExlA), for host cell membrane disruption. Here, we demonstrated that ExlA export requires a predicted outer membrane protein, ExlB, showing that ExlA and ExlB define a new active two-partner secretion (TPS) system of P. aeruginosa. In addition to the TPS signals, ExlA harbors several distinct domains, which include one hemagglutinin domain, five arginine-glycine-aspartic acid (RGD) motifs, and a C-terminal region lacking any identifiable sequence motifs. However, this C-terminal region is important for the toxic activity, since its deletion abolishes host cell lysis. Using lipid vesicles and eukaryotic cells, including red blood cells, we demonstrated that ExlA has a pore-forming activity which precedes cell membrane disruption of nucleated cells. Finally, we developed a high-throughput cell-based live-dead assay and used it to screen a transposon mutant library of an ExlA-producing P. aeruginosa clinical strain for bacterial factors required for ExlA-mediated toxicity. The screen resulted in the identification of proteins involved in the formation of type IV pili as being required for ExlA to exert its cytotoxic activity by promoting close contact between bacteria and the host cell. These findings represent the first example of cooperation between a pore-forming toxin of the TPS family and surface appendages in host cell intoxication.

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Pseudomonas aeruginosa renews its virulence factors

Cited by 55 publications

References 49 publications

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

Pseudomonas aeruginosa Pore-Forming Exolysin and Type IV Pili Cooperate To Induce Host Cell Lysis

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