Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase

Abstract

Bacterial cells sense their population density through a sophisticated cell-cell communication system and trigger expression of particular genes when the density reaches a threshold. This type of gene regulation, which controls diverse biological functions including virulence, is known as quorum sensing. Quorum-sensing signals, such as acyl-homoserine lactones (AHLs), are the essential components of the communication system. AHLs regulate virulence gene expression in a range of plant and animal (including human) bacterial pathogens. AHL-producing tobacco restored the pathogenicity of an AHL-negative mutant of Erwinia carotovora. Different bacterial species may produce different AHLs, which vary in the length and substitution of the acyl chain but contain the same homoserine lactone moiety. Here we show that the acyl-homoserine lactonase (AHL-lactonase), a new enzyme from Bacillus sp., inactivates AHL activity by hydrolysing the lactone bond of AHLs. Plants expressing AHL-lactonase quenched pathogen quorum-sensing signalling and showed significantly enhanced resistance to E. carotovora infection. Our results highlight a promising potential to use quorum-sensing signals as molecular targets for disease control, thereby broadening current approaches for prevention of bacterial infections.

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…Although the aiiA gene did not share significant homology with any known sequences, it did encode an HXHXD sequence motif common to metallo-␤-lactamases. Purified AiiA protein inactivated multiple AHLs in vitro (57), and biochemical analysis confirmed that AiiA functioned as a lactonase (85). Importantly, when cloned into the plant pathogen Erwinia carotovora, the aiiA gene reduced AHL release from the pathogen, decreased QS-controlled enzyme activities, and reduced soft rot disease symptoms on potato, eggplant, Chinese cabbage, carrot, and celery plants (57).…”

“…Many transgenic plant species expressing AiiA have been shown to be more resistant to soft rot disease (85,91,92); however, the use of such plants in food production has been met with strong resistance from consumers, propelling the development of alternative quorum-quenching approaches. Bacterially mediated quorum quenching using AiiA was also demonstrated to be beneficial against plant pathogens, both when aiiA was expressed in the pathogenic bacterium itself and during coinoculation of the pathogen with bacteria naturally producing AiiA or engineered bacterial strains expressing heterologous AiiA (88,89,(93)(94)(95)(96).…”

“…AHL lactonases are metalloproteins (with the exception of AiiM) that hydrolyze the ester bond of the homoserine lactone ring to yield the corresponding acyl homoserine molecule (Fig. 3) (57,85). Hydrolysis of this ester bond can also occur spontaneously at alkaline pH, and acidic conditions can restore the bond and AHL signaling activity following biological or abiotic hydrolysis (86).…”

Quorum quenching enzyme activity is widely conserved in the sera of mammalian species

“…Production of these AHLs is hierarchically regulated in which threshold levels of 3OC12HSL are required to activate the synthesis of C4HSL [6,7]. Considerable attention has been directed at developing anti-quorum-sensing agents as possible infection control therapeutics [8][9][10]. This approach is particularly attractive in the case of P. aeruginosa because this bacterium could cause life-threatening chronic infections in the individuals with the genetic disease cystic fibrosis.…”

In Vitro Characterization of a Recombinant AHL-Lactonase from Bacillus cereus Isolated from a Striped Catfish (Pangasianodon hypophthalmus) Pond

“…and other species [9,[12][13][14]. Genetically-modified Erwinia carotovora and Pseudomonas aeruginosa expressing AHL-lactonase showed decreased production of virulence factors and attenuated virulence [15,16]. AHL-lactonase has been over-expressed successfully in E. coli and Pichia pastoris expression system as a soluble heterologous protein [17,18].…”