Marine fungi showing multifunctional activity against human pathogenic microbes and cancer

Abstract

Multifunctional drugs have shown great promise in biomedicine. Organisms with antimicrobial and anticancer activity in combination with antioxidant activity need further research. The Red Sea and the Arabian Gulf coasts were randomly sampled to find fungi with multifunctional activity. One hundred strains (98 fungi and 2 lichenized forms) were isolated from 15 locations. One-third of the isolates inhibited clinical bacterial (Staphylococcus aureus, Bacillus subtilis, Vibrio cholerae, Salmonella typhi, S. paratyphi) and fungal pathogens (Talaromycets marneffei, Malassezia globose, Cryptococcus neoformans, Candida albicans, Aspergillus fumigatus) and four cancer cell lines (Hep G2 liver, A-549 lung, A-431skin, MCF 7 breast cancer). Bacterial and cancer inhibition was often accompanied by a high antioxidant activity, as indicated by the principal component analysis (PCA). PCA also indicated that fungal and bacterial pathogens appeared to be inhibited mostly by different marine fungal isolates. Strains with multifunctional activity were found more from the Rea Sea than from the Arabian Gulf coasts. The highest potential for multifunctional drugs were observed for Acremonium sp., Acrocalymma sp., Acrocalymma africana, Acrocalymma medicaginis (activity reported for the first time), Aspergillus sp. Cladosporium oxysporum, Emericellopsis alkaline, Microdochium sp., and Phomopsis glabrae. Lung, skin, and breast cancers were inhibited 85%-97% by Acremonium sp, while most of the isolates showed low inhibition (ca 20%). The highest antifungal activity was observed for Acremonium sp., Diaporthe hubeiensis, Lasiodiplodia theobromae, and Nannizia gypsea. One Acremonium sp. is of particular interest to offer a multifunctional drug; it displayed both antifungal and antibacterial activity combined with high antioxidant activity (DPPH scavenging 97%). A. medicaginis displayed combined antibacterial, anticancer, and antioxidant activity being of high interest. Several genera and some species included strains with both high and low biological activities pointing out the need to study several isolates to find the most efficient strains for biomedical applications.

Fig 1. Location map of the study area (The map is modified from Google maps).

Fig 2. Phylogenetic tree of marine fungi and reference sequence accession numbers constructed by using neighbour joining method in the MEGA 5.2 program.

Fig 3

a. Loading’s of variables in PCA where marine fungal metabolites were measured for their inhibitory effect against bacteria, fungi, and cancer and their DPPH scavenging activity and reducing power. b. PCA sample score plot of marine fungal species. c. PCA sample score plot of marine fungal species marked according to their sampling location on the coast of the Red Sea (R) or the Arabian Gulf (A).

Fig 4. Inhibition (zone of inhibition, mean and error bar for SD) of five pathogenic bacteria (in colors) by the metabolites of the marine fungi isolated from the coasts of the Red Sea and the Arabian Gulf.

Mean refers to the mean of all isolates tested. Letters after the species names refer to the isolate code in Table 1.

Fig 5. Inhibition (zone of inhibition, mean and error bar for SD) of five pathogenic fungi (in colors) by the metabolites of the marine fungi isolated from the coasts of the Red Sea and the Arabian Gulf.

Mean refers to the mean of all isolates tested.