<i>Pseudomonas aeruginosa</i>: new insights into pathogenesis and host defenses

Gellatly, Shaan L.; Hancock, Robert E. W.

doi:10.1111/2049-632x.12033

Cited by 1,071 publications

(985 citation statements)

References 130 publications

(180 reference statements)

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“…Bac7 and its BODIPY fluorescently labeled derivative [Bac7 -BY] were prepared as previously described (14). Bac5(1-31) and BMAP27 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) were chemically synthesized as previously described (41). Apidaecin 137 and oncocin 112 were generously provided by Ralf Hoffmann (13,42).…”

Section: Methodsmentioning

confidence: 99%

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The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

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Pseudomonas aeruginosa infections represent a serious threat to worldwide health. Proline-rich antimicrobial peptides (PR-AMPs), a particular group of peptide antibiotics, have demonstrated in vitro activity against P. aeruginosa strains. Here we show that the mammalian PR-AMP Bac7(1-35) is active against some multidrug-resistant cystic fibrosis isolates of P. aeruginosa. By confocal microscopy and cytometric analyses, we investigated the mechanism of killing against P. aeruginosa strain PAO1 and three selected isolates, and we observed that the peptide inactivated the target cells by disrupting their cellular membranes. This effect is deeply different from that previously described for PR-AMPs in Escherichia coli and Salmonella enterica serovar Typhimurium, where these peptides act intracellularly after having been internalized by means of the transporter SbmA without membranolytic effects. The heterologous expression of SbmA in PAO1 cells enhanced the internalization of Bac7(1-35) into the cytoplasm, making the bacteria more susceptible to the peptide but at the same time more resistant to the membrane lysis, similarly to what occurs in E. coli. The results evidenced a new mechanism of action for PRAMPs and indicate that Bac7 has multiple and variable modes of action that depend on the characteristics of the different target species and the possibility to be internalized by bacterial transporters. This feature broadens the spectrum of activity of the peptide and makes the development of peptide-resistant bacteria a more difficult process.

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Section: Methodsmentioning

confidence: 99%

“…These infections demonstrate high morbidity and mortality for the limited therapies, in particular due to the spread of antimicrobial-resistant strains (17). For these reasons, finding alternative prevention and treatment strategies is an urgent priority (18).…”

mentioning

confidence: 99%

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Runti

Benincasa

Giuffrida

et al. 2017

Antimicrob Agents Chemother

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“…From such examples, we can understand the processes driving the formation and breakdown of biofilm communities. However, many such communities persist for long periods, over many generations (8,10,11). Understanding microbial phenotypes, therefore, also requires us to study the processes that affect cells within these dense communities.…”

mentioning

confidence: 99%

Importance of positioning for microbial evolution

Kim

Racimo

Schluter

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

143

207

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Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring. Here we show that spontaneous mutants repeatedly arise, push their way to the surface, and dominate colonies of the bacterium Pseudomonas fluorescens Pf0-1. Microscopy and modeling suggests that these mutants use secretions to expand and push themselves up to the growth surface to gain the best access to oxygen. Physically mixing the cells in the colony, or introducing space limitations, largely removes the mutant's advantage, showing a key link between fitness and the ability of the cells to position themselves in the colony. We next follow over 500 independent adaptation events and show that all occur through mutation of a single repressor of secretions, RsmE, but that the mutants differ in competitiveness. This process allows us to map the genetic basis of their adaptation at high molecular resolution and we show how evolutionary competitiveness is explained by the specific effects of each mutation. By combining population level and molecular analyses, we demonstrate how living in dense microbial communities can generate strong natural selection to reach the growing edge.bacteria | biofilm | experimental evolution | social interaction

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“…WT, PAO1 wild-type; DeprS, PAO1DeprS; +empty, complemented with pBBR1MCS-2;+eprS WT, complemented with pBBR1-eprS WT; +eprS S308A, complemented with pBBR1-eprS S308A. (Gellatly & Hancock, 2013;Nadal Jimenez et al, 2012). As shown by the results in Fig.…”

Section: Phenotypic Characterization Of Pao1deprsmentioning

confidence: 99%

“…The pathogenesis of P. aeruginosa infections is obviously multifactorial as suggested by the large number of both cell-associated and extracellular virulence factors, and the broad spectrum of diseases due to the bacterium (Gellatly & Hancock, 2013;Gooderham & Hancock, 2009). Cellassociated virulence factors include flagella, type IV pili and alginate; extracellular virulence factors include exotoxin A, pyocyanin, haemolysins, proteases and type III secretion effectors.…”

Section: Introductionmentioning

confidence: 99%

EprS, an autotransporter serine protease, plays an important role in various pathogenic phenotypes of Pseudomonas aeruginosa

2016

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Pseudomonas aeruginosa possesses an arsenal of both cell-associated (flagella, pili, alginate, etc.) and extracellular (exotoxin A, proteases, type III secretion effectors, etc.) virulence factors. Among them, secreted proteases that damage host tissues are considered to play an important role in the pathogenesis of P. aeruginosa infections. We previously reported that EprS, an autotransporter protease of P. aeruginosa, induces host inflammatory responses through protease-activated receptors. However, little is known about the role of EprS as a virulence factor of P. aeruginosa. In this study, to investigate whether EprS participates in the pathogenicity of P. aeruginosa, we characterized various pathogenic phenotypes of the wild-type PAO1 strain and its eprS-disrupted mutant. The growth assays demonstrated that the growth of the eprS mutant was somewhat lower than that of the wild-type strain in a minimal medium containing BSA as the sole carbon and nitrogen source. Thus, these results indicate that eprS would have a role in the growth of P. aeruginosa in the presence of limited nutrients, such as a medium containing proteinaceous materials as a sole nutrient source. Furthermore, disruption of eprS resulted in a decreased production of elastase, pigments, autoinducers and surfactants, and a reduction of swimming and swarming motilities. In addition, the eprS mutant exhibited a reduction in the ability to associate with A549 cells and an attenuation of virulence in leucopenic mice as compared with the wild-type strain. Collectively, these results suggest that EprS exerts pleiotropic effects on various pathogenic phenotypes of P. aeruginosa.

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Pseudomonas aeruginosa: new insights into pathogenesis and host defenses

Cited by 1,071 publications

References 130 publications

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

Importance of positioning for microbial evolution

EprS, an autotransporter serine protease, plays an important role in various pathogenic phenotypes of Pseudomonas aeruginosa

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