Comparison of <i>Pseudomonas aeruginosa</i> strains reveals that Exolysin A toxin plays an additive role in virulence

Medina-Rojas, Maria; Stribling, William; Snesrud, Erik; Garry, Brittany; Li, Yuanzhang; McGann, Patrick; Demons, Samandra; Tyner, Stuart D.; Zurawski, Daniel V.; Antonic, Vlado

doi:10.1093/femspd/ftaa010

Cited by 17 publications

(23 citation statements)

References 45 publications

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“…Under nonlimiting iron conditions, P. aeruginosa no longer releases pyoverdine but uses pyocyanin (5-N-methyl-1-hydroxyphenazine) as a major antifungal molecule (Sass et al, 2021). Finally, Pseudomonas toxins, such as exotoxin A, could participate in antifungal activity (Medina-Rojas et al, 2020). All of the studies cited (Sass et al, 2017;Sass et al, 2019;Sass et al, 2021) on the direct intermicrobial competition between these two major pathogens were performed using planktonic filtrates of P. aeruginosa, and measuring fungal biofilm metabolism as the target.…”

Section: Introductionmentioning

confidence: 99%

Altered Pseudomonas Strategies to Inhibit Surface Aspergillus Colonies

Sass¹,

Nazik²,

Chatterjee³

et al. 2021

Front. Cell. Infect. Microbiol.

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Pseudomonas aeruginosa and Aspergillus fumigatus infections frequently co-localize in lungs of immunocompromised patients and individuals with cystic fibrosis (CF). The antifungal activity of P. aeruginosa has been described for its filtrates. Pyoverdine and pyocyanin are the principal antifungal P. aeruginosa molecules active against A. fumigatus biofilm metabolism present in iron-limited or iron-replete planktonic P. aeruginosa culture filtrates, respectively. Using various P. aeruginosa laboratory wild-type strains (PA14, PAO1, PAK), we found antifungal activity against Aspergillus colonies on agar. Comparing 36 PA14 and 7 PAO1 mutants, we found that mutants lacking both major siderophores, pyoverdine and pyochelin, display higher antifungal activity on agar than their wild types, while quorum sensing mutants lost antifungal activity. Addition of ferric iron, but not calcium or magnesium, reduced the antifungal effects of P. aeruginosa on agar, whereas iron-poor agar enhanced antifungal effects. Antifungal activity on agar was mediated by PQS and HHQ, via MvfR. Among the MvfR downstream factors, rhamnolipids and elastase were produced in larger quantities by pyoverdine–pyochelin double mutants and showed antifungal activity on agar. In summary, antifungal factors produced by P. aeruginosa on agar differ from those produced by bacteria grown in liquid cultures, are dependent on quorum sensing, and are downregulated by the availability of ferric iron. Rhamnolipids and elastase seem to be major mediators of Pseudomonas’ antifungal activity on a solid surface.

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Section: Introductionmentioning

confidence: 99%

Altered Pseudomonas Strategies to Inhibit Surface Aspergillus Colonies

Sass¹,

Nazik²,

Chatterjee³

et al. 2021

Front. Cell. Infect. Microbiol.

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“…exlA + strains have been isolated in patients with different types of infectious disease [ 6 , 18 , 19 ] and are widespread in the environment [ 6 , 20 ]. In most reported studies on exlA + outliers, strain identification has been performed by genetic analysis of the isolates, but did not measure the amounts of secreted ExlA, a crucial parameter to determine strain virulence.…”

Section: Introductionmentioning

confidence: 99%

ExlA Pore-Forming Toxin: Localization at the Bacterial Membrane, Regulation of Secretion by Cyclic-Di-GMP, and Detection In Vivo

Deruelle

Berry

Bouillot

et al. 2021

Toxins

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ExlA is a highly virulent pore-forming toxin that has been recently discovered in outlier strains from Pseudomonas aeruginosa. ExlA is part of a two-partner secretion system, in which ExlA is the secreted passenger protein and ExlB the transporter embedded in the bacterial outer membrane. In previous work, we observed that ExlA toxicity in a host cell was contact-dependent. Here, we show that ExlA accumulates at specific points of the outer membrane, is likely entrapped within ExlB pore, and is pointing outside. We further demonstrate that ExlA is maintained at the membrane in conditions where the intracellular content of second messenger cyclic-di-GMP is high; lowering c-di-GMP levels enhances ExlB-dependent ExlA secretion. In addition, we set up an ELISA to detect ExlA, and we show that ExlA is poorly secreted in liquid culture, while it is highly detectable in broncho-alveolar lavage fluids of mice infected with an exlA+ strain. We conclude that ExlA translocation is halted at mid-length in the outer membrane and its secretion is regulated by c-di-GMP. In addition, we developed an immunological test able to quantify ExlA in biological samples.

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“…Larvae experiments were performed according to the method previously described [25]. The serial dilutions of bacteria used to inoculate the larvae were plated onto regular LB plates to determine colony forming units (CFU) ml −1 for each strain.…”

Section: G Mellonella Infectionsmentioning

confidence: 99%

Vfr or CyaB promote the expression of the pore-forming toxin exlBA operon in Pseudomonas aeruginosa ATCC 9027 without increasing its virulence in mice

et al. 2021

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Pseudomonas aeruginosa is a wide-spread γ-proteobacterium that produces the biosurfactant rhamnolipid that has a great commercial value due to excellent properties of low toxicity and high biodegradability. However, this bacterium is an opportunist pathogen that constitutes an important health hazard due to its production of virulence-associated traits and its high antibiotic resistance. Thus, it is highly desirable to have a non-virulent P. aeruginosa strain for rhamnolipid production. It has been reported that strain ATCC 9027 is avirulent in mouse models of infection, and it is still able to produce rhamnolipid. Thus, it has been proposed to be suitable for it industrial production, since it encodes a defective LasR quorum sensing (QS) transcriptional regulator that is the head of this regulatory network. However, the restoration of virulence factor production by overexpression of rhlR (the gene encoding a QS-transcriptional regulator which is under the transcriptional control of LasR) is not sufficient to restore its virulence in mice. It is desirable to obtain a deeper understanding of ATCC 9027 attenuated-virulence phenotype and to assess the safety of this strain to be used at an industrial scale. In this work we determined whether increasing the expression of the pore-forming toxin encoded by the exlBA operon in strain ATCC 9027 had an impact on its virulence using Galleria mellonella and mouse models of infections. We increased the expression of the exlBA operon by overexpressing from a plasmid its transcriptional activator Vfr or of the Vfr ligand cyclic AMP produced by CyaB. We found that in G. mellonella ATCC 9027/pUCP24-vfr and ATCC 9027/pUCP24-cyaB gained a virulent phenotype, but these strains remained avirulent in murine models of P. aeruginosa infection. These results reinforce the possibility of using ATCC 9027 for industrial biosurfactants production.

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Comparison of Pseudomonas aeruginosa strains reveals that Exolysin A toxin plays an additive role in virulence

Cited by 17 publications

References 45 publications

Altered Pseudomonas Strategies to Inhibit Surface Aspergillus Colonies

Altered Pseudomonas Strategies to Inhibit Surface Aspergillus Colonies

ExlA Pore-Forming Toxin: Localization at the Bacterial Membrane, Regulation of Secretion by Cyclic-Di-GMP, and Detection In Vivo

Vfr or CyaB promote the expression of the pore-forming toxin exlBA operon in Pseudomonas aeruginosa ATCC 9027 without increasing its virulence in mice

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