Antifungal Bioactivity Research Articles

A chromatogram-simplified Streptomyces albus host for heterologous production of natural products

Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.

Enantioselective total synthesis, divergent optimization and preliminary biological evaluation of (indole-N-alkyl)-diketopiperazines.

The first enantioselective total synthesis of the antifungal natural product (indole-N-isoprenyl)-tryptophan-valine diketopiperazine 5 was accomplished. Four stereoisomers of 5 were intentionally prepared, and the (R, R)-isomer is more favorable in enhancing the antifungal bioactivity. Divergent structural optimization of this attractive model was conducted from the chiral pool amino acids. Fine-tuning of the structure protruded the broad-spectrum antifungal 6b, which also showed good preventative efficacy against Sclerotinia scleotiorum. Compound 5d could accelerate both hypocotyl elongation and root growth of Eclipta prostrata even at the concentration of <2.5 ppm. This unique and easily accessible scaffold will be of prime importance in achieving agrochemical candidates with the novel scaffold.

Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin.

In this study, we report antifungal activity of auroramycin against Candida albicans, Candida tropicalis, and Cryptococcus neoformans. Auroramycin, a potent antimicrobial doubly glycosylated 24-membered polyene macrolactam, was previously isolated and characterized, following CRISPR-Cas9 mediated activation of a silent polyketide synthase biosynthetic gene cluster in Streptomyces rosesporous NRRL 15998. Chemogenomic profiling of auroramycin in yeast has linked its antifungal bioactivity to vacuolar transport and membrane organization. This was verified by disruption of vacuolar structure and membrane integrity of yeast cells with auroramycin treatment. Addition of salt but not sorbitol to the medium rescued the growth of auroramycin-treated yeast cells suggesting that auroramycin causes ionic stress. Furthermore, auroramycin caused hyperpolarization of the yeast plasma membrane and displayed a synergistic interaction with cationic hygromycin. Our data strongly suggest that auroramycin inhibits yeast cells by causing leakage of cations from the cytoplasm. Thus, auroramycin’s mode-of-action is distinct from known antifungal polyenes, reinforcing the importance of natural products in the discovery of new anti-infectives.

Phytochemical Analysis and Antifungal bioactivity of Pulicaria undulata (L.) Methanolic Extract and Essential Oil

PULICARIA UNDULATA is one of the aromatic annual herbs used in folk medicine in Egypt. The aerial parts of P. undulata plants were collected from the Red sea coastal desert during the flowering stage and used for phytochemical analysis. It was revealed that P. undulata aerial portions contain phenols, flavonoids terpenoids, saponins, alkaloids, glucosinolates and cardiac glycosides highlighting its participation in drug development and using as an alternative strategy to the harmful synthetic fungicides. The greater accumulation of the bioactive compounds in the methanolic extract was comparable with its higher antioxidant capacity and IC50 value as compared with those of the petroleum ether extract. The GC-MS analysis revealed the occurrence of ten bioactive phytocomponents including cyclotrisiloxane, hexamethyl-, cyclotetrasiloxane, octamethyl-, cyclopentasiloxane, decamethyl, dodecanoic acid, methyl ester, tetrafluorophthalonitrile, gamma-Sitosterol, nonacosane, 4,4,6a,6b,8a,11,11,14b-Octamethyl ,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydro-2H-picen-3-one, thiazolo[4,5-f]quinoline and 7-methyl-. In addition, the methanolic extract exhibited antifungal activity against the investigated six pathogenic fungal strains: Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Microsporum canis, Microsporum boulardii and Trichophyton mentagrophytes. Based on the values of the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC), the methanolic extract has demonstrated a fungicidal effect on M. boulardii IFM 56403, T. mentagrophytes AUMC 11661, M. canis AUMC 11663, and C. albicans AUMC 9142. The cytotoxicity evaluation of the methanolic extract showed safe levels in case of these four fungal strains. The petroleum ether extract, inhibited the tested fungi but with lower efficiency. Our results suggest the promising antifungal activity of P. undulata on medically important fungi.

Inhibition of Tomato Early Blight Disease by Culture Extracts of a Streptomyces puniceus Isolate from Mangrove Soil.

This study investigates the potential of natural products derived from a mangrove rhizosphere bacterium in tomato early blight management. A Streptomyces puniceus strain L75 was isolated from the rhizosphere of Acanthus ilicifolius Linn in the Mai Po Reserve, Hong Kong. The crude ethyl acetate (EA) extract of L75 fermentation cultures has broad-spectrum antifungal bioactivities. L75 EA extract was significantly more effective in Alternaria solani growth inhibition at 25 μg/ml or lower compared with Mancozeb, with no observable negative impacts on tomato leaves or root development. Furthermore, L75 EA extract had significantly lower aquatic toxicity than Mancozeb at the same concentrations. L75 EA extract targets germ tube elongation of A. solani conidia, with a fungistatic mode of action. Liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified two possible antifungal compounds, Alteramide A and the Heat-Stable Antifungal Factor, which together contribute partially to the bioactivity of L75 EA extract. On detached tomato leaves, coinoculation of A. solani with L75 EA extract of 50, 25, or 5 μg/ml reduced diseased areas by ∼98, ∼90, and ∼48%, respectively, relative to the control after 5 days. This study demonstrates the potential of natural products from mangrove rhizosphere bacteria in agricultural applications.

Inhibition of Leucoagaricus gongylophorus with Carica papaya: an alternative to control the leaf-cutter ant Acromyrmex octospinosus

The symbiotic association of the leaf-cutter ants with the fungus Leucoagaricus gongylophorus implies that the negative impact on the fungi will affect the survival of the ants. After a promising antifungal bioactivity, Carica papaya was studied leading to the bioassay-guided isolation of squalene, 4,5-dihydrohumulen, the flavanol-glycosides quercetin, kaempferol, and rutin, and the alkaloid carpaine. Carpaine and squalene were found to have a moderate individual activity, which increased when evaluated together. Based on the presence of these compounds, standardized extracts were formulated for field tests on nests of Acromyrmex octospinosus. All the nests treated were negatively affected evidencing a promising lead for the integrated management of leaf-cutter ants.

Indexing Natural Products for their Antifungal Activity by Filters-based Approach: Disclosure of Discriminative Properties.

A considerable worldwide increase in the rate of invasive fungal infections and resistance toward antifungal drugs was witnessed during the past few decades. Therefore, the need for newer antifungal candidates is paramount. Nature has been the core source of therapeutics for thousands of years, and an impressive number of modern drugs including antifungals were derived from natural sources. In order to facilitate the recognition of potential candidates that can be derived from natural sources, an iterative stochastic elimination optimization technique to index natural products for their antifungal activity was utilized. A set of 240 FDA-approved antifungal drugs, which represent the active domain, and a set of 2,892 natural products, which represent the inactive domain, were used to construct predictive models and to index natural products for their antifungal bioactivity. The area under the curve for the produced predictive model was 0.89. When applying it to a database that is composed of active/inactive chemicals, we succeeded to detect 42% of the actives (antifungal drugs) in the top one percent of the screened chemicals, compared with one-percent when using a random model. Eight natural products, which were highly scored as likely antifungal drugs, are disclosed. Searching PubMed showed only one molecule (Flindersine) out of the eight that have been tested was reported as an antifungal. The other seven phytochemicals await evaluation for their antifungal bioactivity in a wet laboratory.

C-Nucleoside Formation in the Biosynthesis of the Antifungal Malayamycin A

Malayamycin A is an unusual bicyclic C-nucleoside, with interesting antiviral, antifungal, and anticancer bioactivity. We report here the discovery and characterization of the biosynthetic pathway to malayamycin by using genome mining of near-identical clusters both from the known producer Streptomyces malaysiensis and from Streptomyces chromofuscus. The key precursor 5'-pseudouridine monophosphate (5'-Ψ-MP) is supplied chiefly through the action of MalD, a TruD-like pseudouridine synthase. Invitro assays showed that MalO is an enoylpyruvyltransferase acting almost exclusively on 5'-Ψ-MP rather than 5'-UMP, while in contrast the counterpart enzyme NikO in the nikkomycin pathway readily accepts either substrate. As a result, deletion of malD in S. chromofuscus coupled with introduction of the gene for NikO led to production of non-natural N-malayamycin, as well as malayamycin A. Conversely, cloning malO into the nikkomycin producer Streptomyces tendae in place of nikO diverted biosynthesis toward C-nucleoside formation.

A suitable vegetative propagation technique for effective fruiting and conservation of a vulnerable medicinal plant, Paris polyphylla smit

Paris polyphylla belongs to the family of Melanthiaceae. The herb has many medicinal properties like anticancer, antibacterial, and antifungal bioactivities. This has led to an unsustainable collection of rhizomes from the wild and pushed the herb to the edge of vulnerability. Therefore, innovative and efficient propagation both in vivo and in vitro is urgent for conservation. The paper illustrates an effective and simple method of sprouting and fruiting formation for conservation of this species through vegetative propagation using various plant growth hormones such as indole-3-butyric acid (IBA), naphthalene acetic acid (NAA), 6-benzylaminopurine (BAP), combination of BAP and NAA at different concentrations (0, 50, 100, 150 mg/l), propagation in the wild, and in the polyhouse using decayed wood, black soil and sand in the ratio 2: 2: 1. Results of the combination of 100 mg/l BAP and 100 mg/l NAA showed the highest percentage of sprouting (93.33%) and fruiting (53.33%). The cultivation in the polyhouse demonstrated a significant percentage of sprouting (93.46%) and fruiting of this species (83.56%).

Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles.

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.

Antibacterial, antifungal and antiviral bioactivities of selected Helichrysum species

Helichrysum species are used widely to treat various medical conditions. In the present study, 14 extracts obtained from 7 Helichrysum species such as H. araxinum Takht. ex Kirp., H. armenium DC, H. arenarium, H. pallasii, H. stoechas, H. sanguineum, and H. graveolens (Asteraceae) were screened for their in vitro antibacterial, antifungal, and antiviral activities. Antibacterial and antifungal activities were evaluated against both standard and isolated strains of Gram negative (E. coli, P. aeruginosa, P. mirabilis, K. pneumoniae, A. baumanni) and Gram positive (S. aureus, E. faecalis) bacteria, as well as fungi (Candida albicans, C. parapsilosis) by microdilution method. We performed susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS). As human pathogens both Herpes simplex virus Type-1 (HSV-1), a DNA virus, and Parainfluenza-3 virus (PI-3), an RNA virus, were employed for antiviral assessment of the water and ethanol extracts of Helichrysum species by using Madin-Darby Bovine Kidney and Vero cell line. All the extracts showed more potent antibacterial activity against Gram positive bacteria (ranging between 16 and 64 μg/mL) than Gram negative (8–64 μg/mL), while showing considerable antifungal activity at 8 μg/mL concentration. Antifungal activities of the extracts were found to be close to antifungal agents in routine clinical use. In particular, all of the ethanolic extracts were found to show better inhibition against S. aureus with a MIC value of 8 μg/mL. In the meantime, ethanolic extracts of H. arenarium and H. armenium DC showed notable antiviral activity against both HSV-1 and PI-3; at a range of 2–32 and 4–64 μg/mL, respectively, by the absence of cytophatic effect. All activities were evaluated at nontoxic concentrations. Helichrysum arenarium and H. armenium DC were found to be the most remarkable species among the tested extracts in terms of bioactivity.

An ATP-Dependent Ligase with Substrate Flexibility Involved in Assembly of the Peptidyl Nucleoside Antibiotic Polyoxin

Polyoxin (POL) is an unusual peptidyl nucleoside antibiotic, in which the peptidyl moiety and nucleoside skeleton are linked by an amide bond. However, their biosynthesis remains poorly understood. Here, we report the deciphering of PolG as an ATP-dependent ligase responsible for the assembly of POL. A polG mutant is capable of accumulating multiple intermediates, including the peptidyl moiety (carbamoylpolyoxamic acid [CPOAA]) and the nucleoside skeletons (POL-C and the previously overlooked thymine POL-C). We further demonstrate that PolG employs an ATP-dependent mechanism for amide bond formation and that the generation of the hybrid nucleoside antibiotic POL-N is also governed by PolG. Finally, we determined that the deduced ATP-binding sites are functionally essential for PolG and that they are highly conserved in a number of related ATP-dependent ligases. These insights have allowed us to propose a catalytic mechanism for the assembly of peptidyl nucleoside antibiotic via an acyl-phosphate intermediate and have opened the way for the combinatorial biosynthesis/pathway engineering of this group of nucleoside antibiotics.IMPORTANCE POL is well known for its remarkable antifungal bioactivities and unusual structural features. Actually, elucidation of the POL assembly logic not only provides the enzymatic basis for further biosynthetic understanding of related peptidyl nucleoside antibiotics but also contributes to the rational generation of more hybrid nucleoside antibiotics via synthetic biology strategy.

Bioactivity-Guided Metabolite Profiling of Feijoa ( Acca sellowiana) Cultivars Identifies 4-Cyclopentene-1,3-dione as a Potent Antifungal Inhibitor of Chitin Synthesis.

Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa. Two novel cultivars were the most bioactive, and the compound 4-cyclopentene-1,3-dione, detected in these cultivars, was potently antifungal (IC50 = 1-2 μM) against human-pathogenic Candida species. Haploinsufficiency and fluorescencemicroscopy analyses determined that the synthesis of chitin, a fungal-cell-wall polysaccharide, was the target of 4-cyclopentene-1,3-dione. This fungal-specific mechanism was consistent with a 22-70-fold reduction in antibacterial activity. Overall, we identified the agricultural waste product of specific cultivars of feijoa peels as a source of potential high-value antifungal compounds.

Biotechnological Applications of Bioactive Peptides From Marine Sources.

This review is an overview on marine bioactive peptides with promising activities for the development of alternative drugs to fight human pathologies. In particular, we focus on potentially prolific producers of peptides in microorganisms, including sponge-associated bacteria and marine photoautotrophs such as microalgae and cyanobacteria. Microorganisms are still poorly explored for drug discovery, even if they are highly metabolically plastic and potentially amenable to culturing. This offers the possibility of obtaining a continuous source of bioactive compounds to satisfy the challenging demands of pharmaceutical industries. This review targets peptides because of the variety of potent biological activities demonstrated by these molecules, including antiviral, antimicrobial, antifungal, antioxidant, anticoagulant, antihypertensive, anticancer, antidiabetic, antiobesity, and calcium-binding bioactivities. Several of these peptides have already gained recognition as effective drug agents in recent years. We also focus on cutting-edge omic approaches for the discovery of novel compounds for pharmacological applications. With rapid depletion of natural resources, omic technologies may be the solution to efficiently produce a vast variety of novel peptides with unique pharmacological potential.

Genome mining reveals high incidence of putative lipopeptide biosynthesis NRPS/PKS clusters containing fatty acyl-AMP ligase genes inbiofilm-forming cyanobacteria.

Cyanobacterial lipopeptides have antimicrobial and antifungal bioactivities with potential for use in pharmaceutical research. However, due to their hemolytic activity and cytotoxic effects on human cells, they may pose a health issue if produced in substantial amounts in the environment. In bacteria, lipopeptides can be synthesized via several well-evidenced mechanisms. In one of them, fatty acyl-AMP ligase (FAAL) initiates biosynthesis by activation of a fatty acyl residue. We have performed a bioinformatic survey of the cyanobacterial genomic information available in the public databases for the presence of FAAL-containing non-ribosomal peptide synthetase/polyketide synthetase (NRPS/PKS) biosynthetic clusters, as a genetic basis for lipopeptide biosynthesis. We have identified 79 FAAL genes associated with various NRPS/PKS clusters in 16% of 376 cyanobacterial genomic assemblies available, suggesting that FAAL is frequently incorporated in NRPS/PKS biosynthetases. FAAL was present either as a stand-alone protein or fused either to NRPS or PKS. Such clusters were more frequent in derived phylogenetic lineages with larger genome sizes, which is consistent with the general pattern of NRPS/PKS pathways distribution. The putative lipopeptide clusters were more frequently found in genomes of cyanobacteria that live attached to surfaces and are capable of forming microbial biofilms. While lipopeptides are known in other bacterial groups to play a role in biofilm formation, motility, and colony expansion, their functions in cyanobacterial biofilms need to be tested experimentally. According to our data, benthic and terrestrial cyanobacteria should be the focus of a search for novel candidates for lipopeptide drug synthesis and the monitoring of toxic lipopeptide production.

Rearranged Biosynthetic Gene Cluster and Synthesis of Hassallidin E in Planktothrix serta PCC 8927.

Cyanobacteria produce a wide range of natural products with antifungal bioactivity. The cyclic glycosylated lipopeptides of the hassallidin family have potent antifungal activity and display a great degree of chemical diversity. Here, we report the discovery of a hassallidin biosynthetic gene cluster from the filamentous cyanobacterium Planktothrix serta PCC 8927. The hassallidin gene cluster showed heavy rearrangement and marks of genomic plasticity. Nucleotide bias, differences in GC content, and phylogenetic incongruence suggested the acquisition of the hassallidin biosynthetic gene cluster in Planktothrix serta PCC 8927 by horizontal gene transfer. Chemical analyses by liquid chromatography and mass spectrometry demonstrated that this strain produced hassallidin E, a new glycosylated hassallidin variant. Hassallidin E was the only structural variant produced by Planktothrix serta PCC 8927 in all tested conditions. Further evaluated on human pathogenic fungi, hassallidin E showed an antifungal bioactivity. Hassallidin production levels correlated with nitrogen availability, in the only nitrogen-fixing Planktothrix described so far. Our results provide insights into the distribution and chemical diversity of cyanobacterial antifungal compounds as well as raise questions on their ecological relevance.

How to improve antifungal bioactivity: POM and DFT study of some chiral amides derivatives of diacetyl-L-tartaric acid and amines

A computational Petra/Osiris/Molinspiration and Density Functional Theory based model has been developed for the identification of physic–chemical parameters governing the bioactivity of chiral amides derivatives of diacetyl-L-tartaric acid and aromatic amines 4–9 containing combined antifungal pharmacophore sites. The six compounds 4–9 analyzed here were previously experimentally and now virtually screened for their antibacterial/antifungal activity. The highest antifungal activity was obtained for compound 6, which exhibited excellent % inhibition, comparable to Terbinafine. Compound 5, represents increased activity as compared to its isomer 6. The increase of bioactivity from 5 to 6 could be attributed to the existence of pi-charge transfer from para-Bromo-phenyl to its amid group (COδ−--NHδ+), which plays a crucial template role in the organization of antifungal O,O-phramacophore sites. Moreover, it is cheap, has fewer side effects, and its possible inclusions in selective fungal/viral media such as Fusarium, HIV, and Hepatitis B/C have to be questioned.

Lunatin, a novel lectin with antifungal and antiproliferative bioactivities from Phaseolus lunatus billb

A novel lectin with a molecular mass of 24.3kDa, designated Lunatin, was isolated from edible seeds of Phaseolus lunatus billb. The purification scheme consisted of ammonium sulfate precipitation, affinity chromatography, ion exchange chromatography, and gel filtration chromatography. The lectin is a glycoprotein, as determined by staining with periodic acid-Schiff (PAS), and its N-terminal amino acid sequence was determined to be DAVIYRGPGDLHTGS. Lunatin exhibited hemagglutinating activity towards human blood group A erythrocytes, which was mostly preserved up to 50°C and retained at ambient temperature at pH 2.0–11.0. d-fructose, d-galactose, d-glucose, and mannitol were capable of inhibiting its hemagglutinating activity. Lunatin was found to be a metal-dependent protein, as its activity was inhibited by the metallic compounds K2Cr2O7, SnCl2, and LiCl, though it was unaffected by MgCl2, ZnCl2, BaCl2, CuCl2, FeCl3, or CaCl2. In addition, Lunatin exerted potent antifungal activity toward a variety of fungal species, including Sclerotium rolfsii, Physalospora piricola, Fusarium oxysporum, and Botrytis cinerea. Finally, proliferation of K562 leukemia cells was strongly inhibited by Lunatin, with an IC50 of 13.7μM, whereas HeLa and HepG2 cells were only weakly affected. These findings further the identification and understanding of functional factors in edible plant seeds.

Isolation of anti-fungal agent from a soil inhabitant Streptomyces albaduncus-M51 and its efficacy against osmophilic food spoilage by Saccharomyces cerevisiae

Aim: This study was performed to isolate antifungal substance from actinomycetes species found in soil in order to avoid osmophilic food spoilage. Methods: Purified isolates of different actinomycetes collected from soil in Makkah region, Saudi Arabia were screened for their antifungal bioactivity against the unicellular fungal strain, Saccharomyces cerevisiae. The actinomycete isolate that showed the highest fungal inhibition potency was selected and identified. Antifungal metabolite fermented by identified isolate was extracted and minimum inhibitory concentration (MIC) was determined. Food preservative efficacy of the extracted crude fungicide was tested against osmophilic foods spoilage. Results: Among 59 actinomycetes strains, 10 isolates exhibited antifungal efficacy against S. cerevisiae. Only one isolate was the most potent fungicidal and identified as Streptomyces albaduncus-M51. Crude antifungal was extracted and MIC value found to be 25µg/ml against the tested yeast strain. Yeast colonies were completely undetected in treated food samples at crude extract concentration (150µl/100ml for liquid foods and 200µl/100mg for solid samples). Conclusion: The antifungal agent produced by S.albaduncus-M51 demonstrated an obvious inhibitory effect against S. cerevisiae that causes osmophilic foods spoilage.

Screening of Endophytic Fungi from Chlorophyta and Phaeophyta for Antibacterial Activity

Chlorophyta and Phaeophyta macroalgae are important sources of secondary metabolites with pharmaceutically relevant antibacterial, antifungal and antiviral bioactivities. Oftentimes, these algae-derived compounds are, in fact, produced by endophytic fungi living inside the macroalgal tissue. Numerous studies have shown that endophytic fungi can produce a broad range of active metabolites such as terpenes, alkaloids, and quinones. The aim of the present study was to screen fungal strains isolated from a variety of Caulerpa spp., Halimeda spp., and Sargassum spp. for antibacterial activity against Staphylococcus aureus and Escherichia coli. Thirteen morphologically different isolates were tested. Two of them showed pronounced activity against S. aureus in agar diffusion assays.