Endophytic fungi are symptomless internal inhabits of plant tissues. They are implicated in the production of antibiotic and other compounds of therapeutic importance. Ecologically they provide several benefits to plants, including protection from plant pathogens. There have been numerous studies on the biodiversity and ecology of endophytic fungi. Some taxa dominate and occur frequently when compared to others due to adaptations or capabilities to produce different primary and secondary metabolites. It is therefore of interest to examine different fungal species and major taxonomic groups to which these fungi belong for bioactive compound production. In the present paper a list of endophytes based on the available literature is reported. More than 800 genera have been reported worldwide. Dominant genera are Alternaria, Aspergillus, Colletotrichum, Fusarium, Penicillium, and Phoma. Most endophyte studies have been on angiosperms followed by gymnosperms. Among the different substrates, leaf endophytes have been studied and analyzed in more detail when compared to other parts. Most investigations are from Asian countries such as China, India, European countries such as Germany, Spain and the UK in addition to major contributions from Brazil and the USA.

Pseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO's critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial strategies such as the inhibition of quorum sensing to alleviate the manifestation of classical resistance mechanisms. Here, we report that 2,4-di-tert-butylphenol (2,4-DBP), isolated from an endophytic fungus, Daldinia eschscholtzii, inhibits the quorum-sensing properties of P. aeruginosa. We have found that treating P. aeruginosa with 2,4-DBP substantially reduced the secretion of virulence factors as well as biofilm, and its associated factors that are controlled by quorum sensing, in a dose-dependent manner. Concomitantly, 2,4-DBP also significantly reduced the expression of quorum sensing-related genes, i.e., lasI, lasR, rhlI, and rhlR significantly. Importantly, 2,4-DBP restricted the adhesion and invasion of P. aeruginosa to the A549 lung alveolar carcinoma cells. In addition, bactericidal assay with 2,4-DBP exhibited synergism with ampicillin to kill P. aeruginosa. Furthermore, our computational studies predicted that 2,4-DBP could bind to the P. aeruginosa quorumsensing receptors LasR and RhlR. Collectively, these data suggest that 2,4-DBP can be exploited as a standalone drug or in combination with antibiotic(s) as an anti-virulence and anti-biofilm agent to combat the multidrug resistant P. aeruginosa infection.

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