Identification of QuiP, the Product of Gene PA1032, as the Second Acyl-Homoserine Lactone Acylase of<i>Pseudomonas aeruginosa</i>PAO1

Huang, Jean J.; Petersen, Ashley; Whiteley, Marvin; Leadbetter, Jared R.

doi:10.1128/aem.72.2.1190-1197.2006

Cited by 155 publications

(142 citation statements)

References 47 publications

Supporting

Mentioning

140

Contrasting

Order By: Relevance

“…Interestingly, homologues of AiiD were also found in various other Ralstonia and Pseudomonas spp. (46), and these bacteria were later confirmed to also possess AHL acylase activity (42,44,45,47,51,52). Biochemical analysis of the fate of 3OC10HSL incubated with purified AiiD protein confirmed that AiiD functions as an AHL acylase, releasing HSL and 3-oxodecanoic acid as the major degradation products (46).…”

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 92%

“…The observation that a pvdQ mutant of PAO1 retained its ability to grow on longchain AHLs suggested that other AHL-degrading enzymes were also employed by P. aeruginosa (42), and additional studies confirmed that two other Ntn hydrolase homologues, QuiP (PA1032) and HacB (PA0305), also function as AHL acylases with substrate specificity similar to that of PvdQ (45,52). Importantly, although PvdQ, QuiP, and HacB were all capable of modulating the accumulation of the endogenous P. aeruginosa signal 3OC12HSL (44,45,52), their abilities to modulate P. aeruginosa behavior and virulence in vivo were distinct. Whereas overproduction of PvdQ in P. aeruginosa or exogenous addition of purified PvdQ protein attenuated Pseudomonas virulence in both fast and slow killing assays in the nematode Caenorhabditis elegans (106), overproduction of HacB showed only limited effects on pathogenesis in nematodes, with differences in virulence being detectable only after 5 days of infection (52).…”

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 95%

“…PvdQ (PA2385) is an AHL aclyase with specificity for long-chain AHLs (42,44), and crystallization studies revealed that AHL hydrolysis proceeds by a mechanism typical of the Ntn hydrolase superfamily (41). The observation that a pvdQ mutant of PAO1 retained its ability to grow on longchain AHLs suggested that other AHL-degrading enzymes were also employed by P. aeruginosa (42), and additional studies confirmed that two other Ntn hydrolase homologues, QuiP (PA1032) and HacB (PA0305), also function as AHL acylases with substrate specificity similar to that of PvdQ (45,52). Importantly, although PvdQ, QuiP, and HacB were all capable of modulating the accumulation of the endogenous P. aeruginosa signal 3OC12HSL (44,45,52), their abilities to modulate P. aeruginosa behavior and virulence in vivo were distinct.…”

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 95%

“…To date, most bacteria known to be capable of AHL inactivation have been found to contain only one or two enzymes responsible for this activity. However, there are exceptions, including P. aeruginosa, which employs multiple AHL acylases (PvdQ, QuiP, HacB, and PA3922) (42,44,45,52). One unique exception is the bacterium Rhizobium sp.…”

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 99%

See 3 more Smart Citations

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

689

556

View full text Add to dashboard Cite

SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

show abstract

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 92%

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 95%

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 95%

Section: Enzymatic Degradation and Inactivation Of Ahlsmentioning

confidence: 99%

See 2 more Smart Citations

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

689

556

View full text Add to dashboard Cite

show abstract

“…Previous studies using transposon insertions on pa0305 revealed that this gene is not crucial for cell growth on C 10 -HSL (Huang et al, 2006). In addition, microarray data published previously (Wagner et al, 2003(Wagner et al, , 2004 did not categorize pa0305 as a QS-regulated gene.…”

Section: Discussionmentioning

confidence: 84%

PA0305 of Pseudomonas aeruginosa is a quorum quenching acylhomoserine lactone acylase belonging to the Ntn hydrolase superfamily

et al. 2011

View full text Add to dashboard Cite

The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomoserine lactone (AHL) acylases. Two additional genes, pa1893 and pa0305, have been predicted to encode penicillin acylase proteins, but have not been characterized. Initial studies on a pa0305 transposon insertion mutant suggested that the gene is not related to the AHL growth phenotype of P. aeruginosa. The close similarity (67 %) of pa0305 to HacB, an AHL acylase of Pseudomonas syringae, prompted us to investigate whether the PA0305 protein might also function as an AHL acylase. The pa0305 gene has been cloned and the protein (PA0305) has been overproduced, purified and subjected to functional characterization. Analysis of the purified protein showed that, like b-lactam acylases, PA0305 undergoes post-translational processing resulting in a-and b-subunits, with the catalytic serine as the first amino acid of the b-subunit, strongly suggesting that PA0305 is a member of the N-terminal nucleophile hydrolase superfamily. Using a biosensor assay, PA0305his was shown to degrade AHLs with acyl side chains ranging in length from 6 to 14 carbons. Kinetics studies using N-octanoyl-L-homoserine lactone (C 8 -HSL) and N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C 12 -HSL) as substrates showed that the enzyme has a robust activity towards these two AHLs, with apparent K cat /K m values of 0.14¾10 4 M "1 s "1 towards C 8 -HSL and 7.8¾10 4 M "1 s "1 towards 3-oxo-C 12 -HSL. Overexpression of the pa0305 gene in P. aeruginosa showed significant reductions in both accumulation of 3-oxo-C 12 -HSL and expression of virulence factors. A mutant P. aeruginosa strain with a deleted pa0305 gene showed a slightly increased capacity to kill Caenorhabditis elegans compared with the P. aeruginosa PAO1 wild-type strain and the PAO1 strain carrying a plasmid overexpressing pa0305. The harmful effects of the Dpa0305 strain on the animals were most visible at 5 days post-exposure and the mortality rate of the animals fed on the Dpa0305 strain was faster than for the animals fed on either the wild-type strain or the strain overexpressing pa0305. In conclusion, the pa0305 gene encodes an efficient acylase with activity towards longchain homoserine lactones, including 3-oxo-C 12 -HSL, the natural quorum sensing signal molecule in P. aeruginosa, and we propose to name this acylase HacB.

show abstract