Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study

Abstract

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.

Isolation and characterization of halophilic and halotolerant fungi from man-made solar salterns in Pattani Province, Thailand

“…It is known that various polyketides, including antibiotics (penicillins), extrolites and penicillic acids, are produced by halophilic strains of Penicillium [ 52 ] and that, antimicrobial compounds such as β-lactam antibiotics from P . chrysogenum and other Penicillium species inhibit most Gram-positive bacteria [ 53 ]. In the light of this existing knowledge, the further characterization and purification of the active metabolites produced by the above six strains of P .…”

“…The isolates P. citrinum NM-3 and A. subalbidus NM-18, NM-19, NM-20, NM-23 and NM-24) proved to be active against the Gram-positive bacteria E. faecalis, M. luteus, S. aureus, S. epidermidis and MRSA, the Gram-negative bacteria E. coli and S. Typhi, the yeast C. albicans and also the human pathogenic fungus A. fumigatus. It is known that various polyketides, including antibiotics (penicillins), extrolites and penicillic acids, are produced by halophilic strains of Penicillium [52] and that, antimicrobial compounds such as β-lactam antibiotics from P. chrysogenum and other Penicillium species inhibit most Gram-positive bacteria [53]. In the light of this existing knowledge, the further characterization and purification of the active metabolites produced by the above six strains of P. citrinum and A. subalbidus are being investigated.…”

Cultivable endophytic fungal community associated with the karst endemic plant Nervilia fordii and their antimicrobial activity

“…The endophytes P. canescens and P. commune showed antimicrobial activities against to the human pathogens ( Gao et al, 2011 ; Malhadas et al, 2017 ) and the phytopathogenic fungi ( Bertinetti et al, 2009 ). Other species, such as P. cinnamopurpureum ( Dinesh et al, 2022 ), P. chrysogenum ( Orfali et al, 2022 ), and P. citrinum ( Kumari et al, 2021 ), had also been reported as being prolific producers of antimicrobial compounds. However, no studies have reported the antibacterial activity of P. macrosclerotiorum , which was identified as a new species of the genus Penicillium in 2017 ( Wang et al, 2007 ; Xu et al, 2021 ).…”

A comprehensive review on the medicinally valuable endosymbiotic fungi Penicillium chrysogenum

“…Orfali et al ( 2022 ) investigated compounds (177–181) obtained from Wadi Lajab sediment-derived fungus P. chrysogenum for their antimicrobial activity with comparison with five types of pathogenic bacteria Staphylococcus aureus, Bacillus licheniformis, Escherichia fergusonii, Enterobacter xiangfangensis, and Ps. aeruginosa .…”