Publication

Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa

Sunder, A. V., Utari, P. D., Ramasamy, S., van Merkerk, R., Quax, W. J. & Pundle, A., Mar-2017, In : Applied Microbiology and Biotechnology. 101, 6, p. 2383-2395 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sunder, A. V., Utari, P. D., Ramasamy, S., van Merkerk, R., Quax, W. J., & Pundle, A. (2017). Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa. Applied Microbiology and Biotechnology, 101(6), 2383-2395. https://doi.org/10.1007/s00253-016-8031-5

Author

Sunder, Avinash Vellore ; Utari, Putri Dwi ; Ramasamy, Sureshkumar ; van Merkerk, Ronald ; Quax, Wim J. ; Pundle, Archana. / Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa. In: Applied Microbiology and Biotechnology. 2017 ; Vol. 101, No. 6. pp. 2383-2395.

Harvard

Sunder, AV, Utari, PD, Ramasamy, S, van Merkerk, R, Quax, WJ & Pundle, A 2017, 'Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa', Applied Microbiology and Biotechnology, vol. 101, no. 6, pp. 2383-2395. https://doi.org/10.1007/s00253-016-8031-5

Standard

Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa. / Sunder, Avinash Vellore; Utari, Putri Dwi; Ramasamy, Sureshkumar; van Merkerk, Ronald; Quax, Wim J.; Pundle, Archana.

In: Applied Microbiology and Biotechnology, Vol. 101, No. 6, 03.2017, p. 2383-2395.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sunder AV, Utari PD, Ramasamy S, van Merkerk R, Quax WJ, Pundle A. Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa. Applied Microbiology and Biotechnology. 2017 Mar;101(6):2383-2395. https://doi.org/10.1007/s00253-016-8031-5


BibTeX

@article{92977827c14741949ab98b441c8a730d,
title = "Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa",
abstract = "Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood. This report details the characterization of AHL degradation activity by homotetrameric PVAs from two gram-negative plant pathogenic bacteria, Pectobacterium atrosepticum (PaPVA) and Agrobacterium tumefaciens (AtPVA). Both the PVAs exhibited substrate specificity for degrading long-chain AHLs. Exogenous addition of these enzymes into Pseudomonas aeruginosa greatly diminished the production of elastase and pyocyanin and biofilm formation and increased the survival rate in an insect model of acute infection. Subtle structural differences in the PVA active site that regulate specificity for acyl chain length have been characterized, which could reflect the evolution of AHL-degrading acylases in relation to the environment of the bacteria that produce them and also provide strategies for enzyme engineering. The potential for using these enzymes as therapeutic agents in clinical applications and a few ideas about their possible significance in microbial physiology have also been discussed.",
keywords = "Penicillin Vacylase, N-acylhomoserine lactone acylase, Ntn hydrolase, Quorum quenching, Pathogenesis, QUORUM-QUENCHING LACTONASES, AGROBACTERIUM-TUMEFACIENS, SUBSTRATE-BINDING, SIGNAL MOLECULES, INFECTION MODEL, IDENTIFICATION, SPECIFICITY, HYDROLASE, ENZYMES, INHIBITION",
author = "Sunder, {Avinash Vellore} and Utari, {Putri Dwi} and Sureshkumar Ramasamy and {van Merkerk}, Ronald and Quax, {Wim J.} and Archana Pundle",
year = "2017",
month = "3",
doi = "10.1007/s00253-016-8031-5",
language = "English",
volume = "101",
pages = "2383--2395",
journal = "Applied Microbiology and Biotechnology",
issn = "0175-7598",
publisher = "SPRINGER",
number = "6",

}

RIS

TY - JOUR

T1 - Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa

AU - Sunder, Avinash Vellore

AU - Utari, Putri Dwi

AU - Ramasamy, Sureshkumar

AU - van Merkerk, Ronald

AU - Quax, Wim J.

AU - Pundle, Archana

PY - 2017/3

Y1 - 2017/3

N2 - Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood. This report details the characterization of AHL degradation activity by homotetrameric PVAs from two gram-negative plant pathogenic bacteria, Pectobacterium atrosepticum (PaPVA) and Agrobacterium tumefaciens (AtPVA). Both the PVAs exhibited substrate specificity for degrading long-chain AHLs. Exogenous addition of these enzymes into Pseudomonas aeruginosa greatly diminished the production of elastase and pyocyanin and biofilm formation and increased the survival rate in an insect model of acute infection. Subtle structural differences in the PVA active site that regulate specificity for acyl chain length have been characterized, which could reflect the evolution of AHL-degrading acylases in relation to the environment of the bacteria that produce them and also provide strategies for enzyme engineering. The potential for using these enzymes as therapeutic agents in clinical applications and a few ideas about their possible significance in microbial physiology have also been discussed.

AB - Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood. This report details the characterization of AHL degradation activity by homotetrameric PVAs from two gram-negative plant pathogenic bacteria, Pectobacterium atrosepticum (PaPVA) and Agrobacterium tumefaciens (AtPVA). Both the PVAs exhibited substrate specificity for degrading long-chain AHLs. Exogenous addition of these enzymes into Pseudomonas aeruginosa greatly diminished the production of elastase and pyocyanin and biofilm formation and increased the survival rate in an insect model of acute infection. Subtle structural differences in the PVA active site that regulate specificity for acyl chain length have been characterized, which could reflect the evolution of AHL-degrading acylases in relation to the environment of the bacteria that produce them and also provide strategies for enzyme engineering. The potential for using these enzymes as therapeutic agents in clinical applications and a few ideas about their possible significance in microbial physiology have also been discussed.

KW - Penicillin Vacylase

KW - N-acylhomoserine lactone acylase

KW - Ntn hydrolase

KW - Quorum quenching

KW - Pathogenesis

KW - QUORUM-QUENCHING LACTONASES

KW - AGROBACTERIUM-TUMEFACIENS

KW - SUBSTRATE-BINDING

KW - SIGNAL MOLECULES

KW - INFECTION MODEL

KW - IDENTIFICATION

KW - SPECIFICITY

KW - HYDROLASE

KW - ENZYMES

KW - INHIBITION

U2 - 10.1007/s00253-016-8031-5

DO - 10.1007/s00253-016-8031-5

M3 - Article

VL - 101

SP - 2383

EP - 2395

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

IS - 6

ER -

ID: 37950903