*5.2.2 Alkylcyclopentanone*

*Bacterial Biofilms*

*5.1.2 Organic acids*

**5.2 From fungi**

*5.2.1 Antibiotics and mycotoxins*

*Variovorax paradoxus*) [50–56].

*(Acinetobacter, Agrobacterium tumefaciens, Alteromonas, Comomonas, Halomonas, Hyphomonas, Klebsiella pneumoniae, P. aeruginosa, Ralstonia, Stappia*, and

Four types of enzymes are known to degrade AHLs [57, 58], a phenomenon sometimes described as "quorum quenching" (QQ ) [59]; these include AHLlactonases and decarboxylases that attack the lactone ring (*Bacillus indicus, B. pumilus*, and *B.* sp. SS4 cause significant inhibition of QS-dependent activities in Gram-negative bacteria such as *P. aeruginosa* PAO1, *Serratia marcescens*, and *Vibrio*), AHL-acylases that cleave the acyl side chain (*B. pumilus* S8-07 degrades 3-oxo-C12- HSL into the corresponding lauric acid [60]), and deaminases that separate the lactone ring from the acyl side chain. Recently, lactonases and acylases were identified in *Erythrobacter, Labrenzia***,** and *Bacterioplanes* found in Red Sea sediments; these both degrade AHLs of different acyl chain lengths, particularly the 3-oxo-C12-HSL,

*Mycobacteroides abscessus* subspecies, emerging pathogens, are capable of degrading both PQS and HHQ. *M. abscessus* subsp. *abscessus*, in coculture with *P. aeruginosa* PAO1, reduced PQS levels through a PQS dioxygenase (encoded by the *aqdC* gene), *M. abscessus* subsp. *massiliense*, a recombinant strain overexpressing the *aqdC* gene, reduces the level of the virulence factors pyocyanin, pyoverdine, and rhamnolipids, suggesting that AqdC is a QQ enzyme [61]. Its impact on biofilm formation would have been interesting to investigate as another dioxygenase, the 2-alkyl-3-hydroxy-4(1H)-quinolone 2,4-dioxygenase (HodC), was described to cleave PQS, attenuate the production of virulence factors but conversely increase the viable biomass, in both newly formed and

The acetic and phenyl lactic acids, found in the supernatant of probiotic strains *Lactobacillus paracasei* subsp. *paracasei* CMGB isolated from newborn feces, were shown to inhibit, at nonbacteriostatic/bactericide levels, the expression of QS genes in *P. aeruginosa*, preventing adherence of bacteria to an inert substratum [63, 64]. Similarly, the lactic acid produced by a potential probiotic *Pediococcus acidilactici* M7 strain, also isolated from newborn feces, inhibits the production of *P. aeruginosa* short-chain AHLs, elastase, protease, pyocyanin, and biofilm as well as the

Penicillin produced by *Penicillium* spp. has been shown to be effective in controlling a bacterial infection. Recently, about 33 *Penicillium* spp. have been recognized as producers of QS inhibitors such as the small lactone mycotoxins patulin and penicillic acid. The use of patulin can significantly reduce lung infection caused by *P. aeruginosa* on a mouse model. Interestingly, a synergy has been shown *in vitro* between patulin and tobramycin toward *P. aeruginosa* PAO1 biofilms, whereas patulin alone does not affect the development of biofilm [66]. Although the antiinfective property of patulin has been demonstrated, its genotoxicity and potential

Erythromycin, a macrolide antibiotic isolated from *Saccharopolyspora erythraea*, has been recently demonstrated to reduce virulence factors in *P. aeruginosa* PAO1, including various motilities, biofilm formation, and production of rhamnolipids, total protease, elastase, and pyocyanin at nonmicrobicidal level (1.6 μg/mL) [68]. Comparably,

carcinogenic properties [67] probably preclude clinical applications.

and inhibit the formation *P. aeruginosa* PAO1 biofilm [59].

established biofilms, by increasing iron availability [62].

swarming-swimming-twitching motilities [65].

**40**

Recently, Kim et al. [77] indicated that the alkylcyclopentanone terrein, isolated from *Aspergillus terreus*, reduced virulence factors (elastase, pyocyanin, and rhamnolipids) and biofilm formation via antagonizing QS receptors without affecting *P. aeruginosa* cell growth. Beyond a negative impact on the production of QS signaling molecules and expression of QS-related genes, terrein also reduced c-di-GMP levels, an important secondary messenger for the switch from planktonic to biofilm lifestyle mode, by decreasing the activity of a diguanylate cyclase required for c-di-GMP biosynthesis [78].

## **5.3 From Plants**
