A homoserine lactone autoinducer regulates virulence of an insect-pathogenic bacterium, Xenorhabdus nematophilus (Enterobacteriaceae)

Abstract

N-␤-Hydroxybutanoyl homoserine lactone (HBHL), the autoinducer of the luminescent system of Vibrio harveyi, has been identified as the first small compound to restore virulence to avirulent mutants of Xenorhabdus nematophilus. HBHL stimulated the level of lipase activity excreted by avirulent X. nematophilus and lowered the phenoloxidase activity in the hemolymph of insects infected with X. nematophilus, parameters that are both associated with insect pathogenesis. Moreover, mortality of the insects infected with avirulent X. nematophilus was restored upon injection with HBHL. Chloroform extraction of medium conditioned with wild-type but not avirulent X. nematophilus led to the isolation of a compound with the same chromatographic mobility as HBHL as well as the ability to stimulate the luminescence of a dim autoinducer-dependent mutant of V. harveyi. Transfer of the V. harveyi lux operon into avirulent and wild-type X. nematophilus generated dim and bright luminescent strains, respectively, which responded to HBHL and an agonist and antagonist in a manner analogous to their effects on the luminescence of dim autoinducer-deficient and bright wild-type strains of V. harveyi, indicating that similar HBHL-dependent regulatory systems exist in these two bacterial species.Xenorhabdus nematophilus is a major insect pathogen that exists in the intestines of the parasitic nematode Steinernema carpocapsae (family Steinernematidae) (1, 9). The high susceptibility of many insect species to infection coupled with the strong reproductive capacity and mobility of the bacteriumnematode complex provides considerable potential for the use of parasitic nematodes for control of insects (11,14). Invasion of the nematodes into the hemocoel of susceptible insect larvae results in the release of the bacteria into the hemolymph; growth of the bacteria and nematodes then results in the rapid death of the insect larvae.Virulence of X. nematophilus and related insect-pathogenic bacteria is due to the expression of an interactive polygenic system comprising tolerance and evasion of the antimicrobial factors of the insect hemolymph (6, 15), changes in bacterial surfaces (6), and the excretion of toxic lipases and lecithinases (7,19). Since insect mortality occurs at a critical concentration of X. nematophilus (6), a density-dependent global regulator may initiate the release of toxic factors (7). Identification of such a regulator could provide the foundation for not only understanding but also controlling virulence of X. nematophilus, which in turn may lead to the development of more effective insect pathogens (11). This paper reports the discovery that the ␤-hydroxybutanoyl homoserine lactone (HBHL) autoinducer, which causes induction of luminescence in the marine bacterium Vibrio harveyi (4), can restore virulence to avirulent mutants of X. nematophilus. The present results also demonstrate that HBHL or a closely related analog is excreted by wild-type and not by avirulent X. nematophilus. MATERIALS AND METHODSStrains and growth conditi...

AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora

“…In recent years, many more bacterial species have been shown to produce AIs (11,17,19,36). Some of them are important plant pathogens such as Pseudomonas and Xanthomonas species.…”

Isolation and Characterization ofN-Acylhomoserine Lactonase from the Thermophilic Bacterium,Geobacillus caldoxylosilyticusYS-8

“…1,2) Besides these activities, quorum sensing plays an important role in controlling the virulence of gene expression in such pathogenic bacteria as Erwinia carotovora, Pseudomonas aeruginosa, and Xenorhabdus nematophilus. 3,4) This regulation is due to a small signaling molecule operating as an auto-inducer which is accumulated, binds to the regulator, and then triggers the physiological expression when it reaches a threshold level for the increase in population density. The gram-negative bacteria use an N-acylhomoserine lactone (AHL) as the quorum sensing signal.…”

AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora

“…In recent years, AIs have been identified in several Gram-negative bacteria. AIs are involved in the regulation of a range of biological functions, including Ti plasmid conjugal transfer in Agrobacterium tumefaciens (3), induction of virulence genes in Erwinia carotovora, Erwinia chrysanthemi, Erwinia stewartii, Pseudomonas aeruginosa, Pseudomonas solanacearum, and Xenorhabdus nematophilus (4)(5)(6)(7)(8)(9)(10)(11)(12), regulation of antibiotic production in Pseudomonas aureofaciens and E. carotovora (10,13), regulation of swarming motility in Serratia liquefaciens (14), and biofilm formation in Pseudomonas fluorescens and P. aeruginosa (15,16). Many more bacterial species are known to produce AIs, but the relevant biological functions have not yet been established (17)(18)(19).…”