Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS) Promotes Biofilm Formation of Pseudomonas aeruginosa by Increasing Iron Availability

Tettmann, Beatrix; Niewerth, Christine; Kirschhöfer, Frank; Neidig, Anke; Dötsch, Andreas; Brenner‐Weiß, Gerald; Fetzner, Susanne; Overhage, J. Marc

doi:10.3389/fmicb.2016.01978

Cited by 23 publications

(21 citation statements)

References 58 publications

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“…The involvement of LasR is further supported by the fact that LasR deleted CF P. aeruginosa isolates were not able to modulate the antiviral response whereas their parental counterpart did. LasR dependent proteases contributing substantially to the virulence of P. aeruginosa are AprA, LasA, LasB, and PrpL (42,43). A limitation of the study is that LasR complemented mutants could not be used.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

et al. 2020

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Cystic fibrosis (CF) patients frequently acquire Pseudomonas aeruginosa infections that have been associated with a bad prognosis and an increased rate of pulmonary exacerbations. Respiratory viruses can cause exacerbations in chronic pulmonary diseases including COPD or asthma and have been suggested to contribute to exacerbations also in CF. In this study we investigated a possible link between P. aeruginosa infection and susceptibility to respiratory viruses. We show that P. aeruginosa is able to block the antiviral response of airway epithelial cells thereby promoting virus infection and spread. Mechanistically, P. aeruginosa secretes the protease AprA in a LasR dependent manner, which is able of directly degrading epithelial-derived IFNλ resulting in inhibition of IFN signaling. In addition, we correlate the virus infection status of CF patients with the ability of patients' P. aeruginosa isolates to degrade IFNλ. In line with this, the infection status of CF patients correlated significantly with the amount of respiratory viruses in sputum. Our data suggest that the interplay between P. aeruginosa and respiratory virus infections might partially explain the association of increased rates of pulmonary exacerbations and P. aeruginosa infections in CF patients.

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Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

et al. 2020

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“…abscessus cannot be excluded. PQS cleavage may be advantageous under certain conditions because PQS, an iron chelator, decreases iron availability (7,30). Further investigations on interspecies interactions are needed to unravel whether aqd genes confer a fitness advantage in natural habitats or in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

“…The enzymes were purified to electrophoretic homogeneity by Ni-nitrilotriacetic acid (NTA) affinity chromatography and stored in 20 mM Tris buffer (pH 8) with 10% (vol/vol) glycerol at Ϫ80°C. Recombinant His-tagged HodC and AqdC1 were purified as described previously (15,30).…”

Section: Methodsmentioning

confidence: 99%

“…3A) (15). A major drawback of HodC for use as a quorum quenching enzyme, besides its low activity for PQS, is its degradation by extracellular proteases produced by P. aeruginosa (13,30). Figure 3B illustrates that HodC is quite stable in pure LB medium at 37°C but rapidly loses activity when incubated in P. aeruginosa cell suspensions.…”

Section: Fig 2 Ahls (A) Aqs (B)mentioning

confidence: 99%

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Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N -Acylhomoserine Lactone Lactonase QsdA

et al. 2019

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The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in cocultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.

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“…massiliense, a recombinant strain overexpressing the aqdC gene, reduces the level of the virulence factors pyocyanin, pyoverdine, and rhamnolipids, suggesting that AqdC is a QQ enzyme [61]. Its impact on biofilm formation would have been interesting to investigate as another dioxygenase, the 2-alkyl-3-hydroxy-4(1H)-quinolone 2,4-dioxygenase (HodC), was described to cleave PQS, attenuate the production of virulence factors but conversely increase the viable biomass, in both newly formed and established biofilms, by increasing iron availability [62].…”

Section: Natural Products That Affect Qs and Biofilm Formation By Psementioning

confidence: 99%

Natural Compounds Inhibiting Pseudomonas aeruginosa Biofilm Formation by Targeting Quorum Sensing Circuitry

Carette¹,

Nachtergael²,

Duez³

et al. 2020

Bacterial Biofilms

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The biofilm lifestyle mode certainly represents one of the most successful behaviors to facilitate bacterial survival in diverse inhospitable environments. Conversely, the ability of bacteria to develop effective biofilms represents one of the major obstacles in the fight against bacterial infections. In Pseudomonas aeruginosa, the biofilm formation is intimately connected to the quorum sensing (QS) mechanisms, a mode of cell-to-cell communication that allows many bacteria to detect their population density in order to coordinate common actions. In this chapter, we propose an overview (i) on P. aeruginosa QS mechanisms and their implication in biofilm formation, and (ii) on natural products that are known to interfere with these QS mechanisms, subsequently disrupting biofilm formation. The concluding remarks focus on perspectives of these compounds as possible antibiotherapy adjuvants.

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Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS) Promotes Biofilm Formation of Pseudomonas aeruginosa by Increasing Iron Availability

Cited by 23 publications

References 58 publications

Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N -Acylhomoserine Lactone Lactonase QsdA

Natural Compounds Inhibiting Pseudomonas aeruginosa Biofilm Formation by Targeting Quorum Sensing Circuitry

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