Role of PvdQ in Pseudomonas aeruginosa virulence under iron-limiting conditions

Nadal‐Jimenez, Pol; Koch, Guillaume; Papaioannou, Evelina; Wahjudi, Mariana; Krzeslak, Joanna; Coenye, Tom; Cool, Robbert H.; Quax, Wim J.

doi:10.1099/mic.0.030973-0

Cited by 98 publications

(114 citation statements)

References 63 publications

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“…PvdQ is an iron-regulated AHL acylase that degrades long-acyl but not short-acyl AHLs (Sio et al, 2006;Nadal et al, 2010). This result may provide an explanation for the previous finding that the level of long-acyl AHLs is greatly reduced in cocultures as compared with P. aeruginosa pure cultures (Figure 3b).…”

Section: Interspecies Competition Triggers Virulencesupporting

confidence: 58%

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

et al. 2014

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Inter-kingdom and interspecies interactions are ubiquitous in nature and are important for the survival of species and ecological balance. The investigation of microbe-microbe interactions is essential for understanding the in vivo activities of commensal and pathogenic microorganisms. Candida albicans, a polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are two opportunistic pathogens that interact in various polymicrobial infections in humans. To determine how P. aeruginosa affects the physiology of C. albicans and vice versa, we compared the proteomes of each species in mixed biofilms versus single-species biofilms. In addition, extracellular proteins were analyzed. We observed that, in mixed biofilms, both species showed differential expression of virulence proteins, multidrug resistance-associated proteins, proteases and cell defense, stress and iron-regulated proteins. Furthermore, in mixed biofilms, both species displayed an increase in mutability compared with monospecific biofilms. This characteristic was correlated with the downregulation of enzymes conferring protection against DNA oxidation. In mixed biofilms, P. aeruginosa regulates its production of various molecules involved in quorum sensing and induces the production of virulence factors (pyoverdine, rhamnolipids and pyocyanin), which are major contributors to the ability of this bacterium to cause disease. Overall, our results indicate that interspecies competition between these opportunistic pathogens enhances the production of virulence factors and increases mutability and thus can alter the course of hostpathogen interactions in polymicrobial infections.

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Section: Interspecies Competition Triggers Virulencesupporting

confidence: 58%

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

et al. 2014

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“…While significant progress has been made with PvdQ and PvdP (5,8,26), the function of any of the proteins encoded by the pvdMNO operon has remained unclear. As interposon mutagenesis suggested essential roles of these proteins for pyoverdine production, it was seemingly not possible to address the individual functions of these enzymes (6,10,11).…”

Section: Discussionmentioning

confidence: 99%

“…The substrate of PvdN is likely to be the glutamic acid form of pyoverdine, which is produced by PvdQ after deacylation of the acylated ferribactin (5,26) immediately after its translocation into the periplasm by PvdE (6). The ⌬pvdN mutant still produces ␣-ketoglutaric acid, which therefore cannot be the product of a PvdN-catalyzed transamination, and because ␣-ketoglutaric acid cannot be transformed to succinamide by a PLP cofactor, it neither can be the substrate for PvdN (Fig.…”

Section: Functional Role Of Pvdnmentioning

confidence: 99%

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

Ringel

Dräger

Brüser

2016

Journal of Biological Chemistry

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Edited by F. Peter GuengerichPyoverdines are high affinity siderophores produced by a broad range of pseudomonads to enhance growth under iron deficiency. They are especially relevant for pathogenic and mutualistic strains that inhabit iron-limited environments. Pyoverdines are generated from non-ribosomally synthesized highly modified peptides. They all contain an aromatic chromophore that is formed in the periplasm by intramolecular cyclization steps. Although the cytoplasmic peptide synthesis and side-chain modifications are well characterized, the periplasmic maturation steps are far from understood. Out of five periplasmic enzymes, PvdM, PvdN, PvdO, PvdP, and PvdQ, functions have been attributed only to PvdP and PvdQ. The other three enzymes are also regarded as essential for siderophore biosynthesis. The structure of PvdN has been solved recently, but no function could be assigned. Here we present the first in-frame deletion of the PvdN-encoding gene. Unexpectedly, PvdN turned out to be required for a specific modification of pyoverdine, whereas the overall amount of fluorescent pyoverdines was not altered by the mutation. The mutant strain grew normally under iron-limiting conditions. Mass spectrometry identified the PvdN-dependent modification as a transformation of the N-terminal glutamic acid to a succinamide. We postulate a pathway for this transformation catalyzed by the enzyme PvdN, which is most likely functional in the case of all pyoverdines.Under aerobic conditions in the neutral pH range, iron can form insoluble Fe III oxide hydrates, limiting the amount of readily available iron. Therefore, many organisms produce siderophores that bind and thereby solubilize iron in their surroundings. A special group of these siderophores are the pyoverdines, yellow-green pigments that were first described in 1892 by Gessard (1). Turfitt (2, 3) used the production of pyoverdines for taxonomic classification of "fluorescent pseudomonads," which include many important pathogenic as well as beneficial pseudomonads. Today it is known that pyoverdines are non-ribosomally synthesized, highly modified peptides whose biosynthesis and regulation involve more than 20 proteins (4). The cytoplasmic biosynthesis reactions are well established, but recently, the periplasmic maturation has gained interest. Of the five periplasmic enzymes, PvdM, PvdN, PvdO, PvdP, and PvdQ, which are found in all known pyoverdine-producing species, functions have been assigned so far only to PvdQ and PvdP, which are involved in a precursor deacylation step and the chromophore cyclization, respectively (5-8). PvdQ has been identified as a potential novel drug target (5). Based on interposon mutagenesis studies, PvdM, PvdN, and PvdO are all considered to be essential for the formation of functional pyoverdines (6, 9 -11).PvdN is translocated via the Tat 2 system (11). As heterologously produced PvdN contains as prosthetic group a pyridoxal phosphate cofactor (PLP (12)), the Tat system may transport PvdN together with a bound PLP or a derivative...

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“…In addition, pvdQ-gene deletion abrogates pyoverdine biosynthesis (38). Although the precise role of PvdQ in this latter pathway is not known, Visca et al (15) have proposed the need for an enzyme that removes a long acyl chain from a pyoverdine precursor.…”

Section: The Catalytic Mechanism Of Pvdq Proceeds Via a Covalently Boundmentioning

confidence: 99%

The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

Bokhove¹,

Nadal‐Jimenez

Quax

et al. 2009

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

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163

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In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N-acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e.g., lactonases or amidohydrolases abolishes AHL regulated virulence, a process known as quorum quenching. Here we report the first crystal structure of an AHL amidohydrolase, the AHL acylase PvdQ from Pseudomonas aeruginosa. PvdQ has a typical α/β heterodimeric Ntn-hydrolase fold, similar to penicillin G acylase and cephalosporin acylase. However, it has a distinct, unusually large, hydrophobic binding pocket, ideally suited to recognize C12 fatty acid-like chains of AHLs. Binding of a C12 fatty acid or a 3-oxo-C12 fatty acid induces subtle conformational changes to accommodate the aliphatic chain. Furthermore, the structure of a covalent ester intermediate identifies Serβ1 as the nucleophile and Asnβ269 and Valβ70 as the oxyanion hole residues in the AHL degradation process. Our structures show the versatility of the Ntn-hydrolase scaffold and can serve as a structural paradigm for Ntn-hydrolases with similar substrate preference. Finally, the quorum-quenching capabilities of PvdQ may be utilized to suppress the quorum-sensing machinery of pathogens.crystal structure | Pseudomonas aeruginosa | quorum sensing | pyoverdine | catalytic mechanism

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Role of PvdQ in Pseudomonas aeruginosa virulence under iron-limiting conditions

Cited by 98 publications

References 63 publications

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

PvdN Enzyme Catalyzes a Periplasmic Pyoverdine Modification

The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

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