Promising sponge derived marine fungi as antibacterial and biofilm inhibitors

INTRODUCTION

Bacterial resistance has become a worldwide problem that endangers the efficacy of existing antibiotics to treat infections, especially with the emergence of multidrug-resistant (MDR) strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR strains of Escherichia coli. Antimicrobial resistance may be attributed to several factors, including the formation of biofilms. Biofilms are complex communities of microorganisms that produce a polymeric extracellular matrix on the surfaces that can inhibit the penetration of antibiotics, making them more resistant than planktonic cells [1–3]. In addition to modifying existing drugs, researchers are looking for new antibiotics by exploring marine organisms. Since the ocean covers about 70% of the earth, it is undeniable that marine environments have more enormous biodiversity compared to terrestrial creatures and contain very promising bioactive compounds to explore. The life of marine organisms varies depending on their surrounding environmental conditions, such as temperature, light, salinity, pressure, and depth of their habitat. They have different evolutionary systems, metabolic pathways, and ecology from terrestrial creatures [4,5], which leads to distinctive chemical composition, complexity, and biological efficacy [6,7].

Marine sponges are known to serve as a source of food and are commonly found throughout the world’s oceans. Sponges are soft, sessile, and able to survive in water with strong currents, since the current provides food and oxygen for its life. They can live in various marine habitats, from shallow to deep seas [8,9]. Sponges are immobile and vulnerable to predators, producing metabolite compounds in self-defense [10]. Many studies report that metabolite compounds contained in sponges have therapeutic activities, including cytotoxic activity [11,12], antimicrobial activity [13,14], antiplasmodial activity [15], and other activities. Given the large potential of sponges as food and medical resources, especially by way of isolating their active compounds, which makes it is necessary to pay attention to the survival of organisms and their environment. Interestingly, sponges can associate with various microbes, both fungi and bacteria. These associated microbes produce metabolites similar to their host but may also create novel active metabolites [16–18]. Some metabolites of sponge-associated microbes have chemical structures similar to terrestrial species, making them a great resource for further exploration, especially as antibacterial agents [19–21].

This review aims to examine isolated metabolite compounds from sponge-associated fungi with antibacterial and biofilm inhibitor activity, including the genus that produces the most active compounds, their antibacterial and antibiofilm potential, and to find out the relationship between antibacterial and biofilm inhibitor activity. The original article used various potential values as a way to compare their antibacterial potential by way of changing its μg/ml units based on the molecular weight. However, the difficult conversion forces it to preserve its original value. This review is expected to assist many researchers in exploring compounds with potential development as new antibacterial and antibiofilm to that “supply issues” to avoid sponge exploitation.

MATERIAL AND METHODS

This review highlights metabolite compounds from fungi associated with sponges exhibiting antibacterial and antibiofilm activity. The data presented were derived from primary articles in English related to keywords “marine” OR “sea” AND “sponge-associated fungi” OR “marine-derive fungi” AND “antibacterial” AND “antibiofilm,” which was discovered in 2002–2022 from Scopus and Pubmed. Variables discussed include genus/species of fungi associated with sponges, species of sponges, metabolite compounds, their potential value, and the type of bacteria being inhibited. The minimum inhibitory concentration (MIC) (units μg/ml or μM) or the diameter of inhibition/DOI (unit mm) of metabolites indicates their ability to inhibit bacterial growth. The potential of antibiofilms is shown by their ability to inhibit the formation of biofilms (% inhibition of biofilms).

Sponge-associated fungi as a source of antibacterial

Many studies reported the activity of sponges, including antimicrobial, cytotoxic, anti-inflammatory, antidiabetic, and antimalarial [22–26]. Microorganisms are closely related to sponge life because of the nature of sea sponges as feeder fillers; their body tissues are related to these microorganisms. These associated microorganisms provide host advantages regarding nutrient supply, skeletal stabilization, regulating waste, and secondary metabolite production [27–30]. Fungi associated with sponges have shown the ability to produce unique and biologically active structures. On this basis, utilizing appropriate biotechnology to isolate metabolite compounds from fungi associated with sponges is likely to be developed as new drugs. Until 2022, there had been 55 articles related to fungi associated with sponges with antibacterial and antibiofilm activity. During these two decades (2002–2022), there was a notable increase in the number of publications (Fig. 1).

The highest publication was found in the 2017–2021 period with 27 articles, which constantly escalated in terms of quantity. Countless scientists were found to show a growing interested in studying sponges associated with microbes, thus indicating a trend considering the need to maintain the existence of sponges. We identified that the most frequently studied families were Trichocomaceae, Hypocreaceae, Herpotrichiellaceae, and Pleosporaceae (Fig. 2), and the genus most commonly studied were Aspergillus, Penicillium, Trichoderma, and Neosartorya (Fig. 3A and B). Some genus were the most prolific sources of antibiotics [31,32].

Figure 1. An overview of research related to sponge-associated fungi with antibacterial and anti-biofilm activity. January 2023*. [Click here to view]

Figure 2. The distribution of the family of sponge-associated fungi with antibacterial and biofilm inhibitors activity (N = 55). [Click here to view]

Figure 3. The distribution of the genus sponge-associated fungi with antibacterial and antibiofilm activity. (A) Family Trichocomaceae (B) Other than Trichocomaceae. [Click here to view]

Genus Aspergillus

Aspergillus contains various chemical metabolites likely to be developed into new drugs, including antimicrobial properties. Marine life contains abundant resources, which thus caught the attention of many researchers. Studies on antibacterial chemicals generated by Aspergillus fungi associated with sponges are presented in Table 1. The compounds of averantine (1) and nidurufin (2) are anthraquinones isolated from the fungus Aspergillus versicolor associated with the sponge Petrosia sp. in the Jeju Sea, Korea. Both of them showed antibacterial activity against gram-positive clinical isolate bacteria, including Staphylococcus aureus SG511, S. aureus 285, S. aureus 503, and most sensitive to Streptococcus pyogenes 308A. Other compounds, including sterigmatocystin, which is a xantone, and methyl-averantin showed potential as potent antitumors against human tumor cells A-549, SK-OV-3, SK-MEL-2, XF-498, HCT-15 indicated by IC₅₀ values ranging from 0.41 to 4.61 μg/ml [33]. The cytotoxic activity of the averantin compound is likely due to the presence of free hydroxyl derivatives, which affect its polarity.

Table 1. Collected data from sponge-associated fungi with antibacterial activity. [Click here to view]

Another strain from A. versicolor is MF359, derived from the sponge Hymeniacidon perleve in the Bohai Sea, China, isolated 5-methoxydihydrosterigmatocystin (3) and showed antibacterial activity against S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633, which are better than the extract by the Minimum Inhibitory Concentration (MIC) values. In terms of its ability as an antibacterial against MRSA (clinical isolate) and Pseudomonas aeruginosa ATCC 15692, the MIC value was >100 μg/ml. This study also has been able to isolate hemiacetal sterigmatocystin, acyl-hemiacetal sterigmatocystin, and aversin [34]. The fungus Aspergilus flavus GU815344 derived from the sponge Callyspongia spp. in the sea of Kovalam, India, generates desmethylnomifensine (GC-MS verified) to serve as an antibacterial against S. aureus and E. coli. The inhibitory power of extracts derived from biomass is smaller than extracts from supernatants based on the diameter clear zone against E. coli and S. aureus bacteria [35]. Similar to the research by Samirana et al. [36], the supernatant extract from Trichoderma reesei TV 221 associated sponge Stylissa flabelliformis showed antibacterial activity better than the biomass extract. Aspergillus flavus IBI 141 and Aspergillus sp IBI 151 associated with the sponge Acanthostrongylophora ingens from Mendeh Island, south coast of West Sumatra, Indonesia, showed antibacterial activity against bacteria B. subtilis, Staphylococcus epidemidis, Salmonella typosa, and E. coli. It also has cytotoxic activity against shrimp larvae, with an LC₅₀ value of 58.56 ppm. The compound class of the fungus A. flavus IBI 141 is phenolics and terpenoids [37].

Several fungi were isolated from the sponge S. flabelliformis, including T. reesei strain JCM 2267, A. flavus strain MC-10-L, Penicillium sp, and Aspergillus fumigatus [38]. Extracts from the fungus were tested for antibacterial ability against S. aureus ATCC 25923, E. coli ATCC 25922, Enterococcus faecalis ATCC 29212, and B. subtilis ATCC 6633. The MIC values of A. flavus fungal extract strain MC-10-L and A. fumigatus are presented in Table 1. The antibacterial activity of A. flavus and A. fumigatus fungi is found to be moderate. The cytotoxic ability of A. flavus strain MC-10-L extract against T47D tumor cells was shown with an IC₅₀ value of 550 (mg/ml). Based on analysis with GC-MS, ethyl acetate extract from the fungus contains cyclohexanone, which requires further research.

The compound preussin (4), as a class of hydroxy pyrrolidine alkaloids, was isolated from the fungus Aspergillus candidus KUFA 0062 associated with the sponge Epipolasis sp. originates from coral reefs in Similan Island National Park in Phang-Nga province, Southern Thailand. This preussin showed better inhibitory activity than its analogues, namely preussin C against bacteria S. aureus ATCC 29213, E. faecalis ATCC 29212, MRSA, and vancomycin-resistant enterococci (VRE). Another activity shown by preussin was inhibited by almost 50% biofilm formation from E. coli ATCC 25922 (42.8% ± 32.7% control), S. aureus ATCC 29213, and E. faecalis ATCC 29212 at concentrations equal to above MIC (Table 2), when preussin was combined with vancomycin antibiotics, oxacillin, and colistin showed a relatively strong synergistic effect. The cytotoxic effect of preussin can reduce the viability of colon cancer cells (6.4% and 8.6% in HCT116 and HT29). The presence of the N-methyl group on the pyrrolidine ring in preussin provides an antibacterial effect and cytotoxic activity. It can serve as a candidate for new antibiotics and anticancers. Other compounds isolated from this fungus are chrysophanic acid and petromurin C [39].

The p-terphenyl alcohol group, 4-O-methylcandidusin A, which was isolated from the fungus A. candidus OUCMDZ-1051, showed a potent and selective cytotoxic effect against MDA-MB-468, BT474, and A431 cancer cells. Its ability to inhibit the growth of E. coli bacteria is demonstrated by the MIC value of 10.0 μg/ml using the dilution method. Hence, it can potentially be developed as an anticancer and antibacterial [40]. Natural p-terphenyls have been widely reported, where the structural diversity is due to variations in ring B, position, and number of hydroxy groups [41,42]. The 16-O-propionyl-16-O-deacetylhelvolic acid (5), 6-O-propionyl-6-O-deacetylhelvolic acid (6), and helvolic acid (7) isolated from the fungus A. fumigatus HNMF0047 effective against Streptococcus agalactiae even though the MIC value was lower than tobramycin as a control. The 6-O-propionyl-6-O-deacetylhelvolic acid has more potent antimicrobial effects than helvolic acid because propionyloxy replaces the acetoxy group at C-6 in helvolic acid [43]. Ethyl acetate extract from the fungus Aspergillus sydowii ZSDS1-F6 fermented using oligotropic medium reported contain sesquiterpenes of bisabolen groups including aspergillusene A, (Z)-5-(Hydroxymenthyl)-2-(6′)-methylhept-2′-en-2′-yl)-phenol, diorcinol, and sydonic acid [44]. Aspergillusene A, (Z)-5-(Hydroxymenthyl)-2-(6′-methylhept-2′-en-2′-yl)-phenol, and diorcinol inhibit the bacterial growth of Klebsiella pneumonia and Aeromonas hydrophila. Except for aspergillusene, both compounds were against H3N2 with IC50 of 57.4 and 66.5 μM. Compounds (Z)-5-(Hydroxymethyl)-2-(6′-methylhept-2′-en-2′-yl)-phenol and (+)-sydonic acid were also found in the fungus Aspergillus sp. associated with the sponge Xestospongia testudinaria in the South China Sea [45]. Based on the identification and elucidation structure, the fungus also contains (−)5-(hydroxymethyl)-2-(2′,6′,6′-trimethyltetrahydro-2H-pyran-2-yl)-phenol, Aspergiterpenoid A, and (+)-sydonol. These compounds show antibacterial activity with MIC values ranging from 1.25 to >20 μM against some bacteria (Table 1). All compounds showed weak cytotoxic effects (IC50 >50 μg/ml) against human promyelocytic leukemia HL-60 and human lung carcinoma cell A-549. None of the compounds showed cholinesterase inhibitory activity.

Sponge Chelonaplysilla sp., which was isolated from 12 fungi-associated were Aspergillus oryzae, Phomompsis sp., Penicillium simplicissimum, Beauveria bassiana, and Aspergillus mellinus [46]. The extracts of A. oryzae and A. mellinus were more sensitive to S. aureus and E. coli, demonstrated by a diameter clear zone ranging from 8.54 to 16.88 mm. The cytotoxic effect is shown by extracts from the fungus Phomompsis sp. with an IC₅₀ value of 83.69 μg/ml. It was concluded that the fungus associated with the sponge Chelonaplysilla sp. can be utilized as a novel antibacterial and anticancer therapeutic agent. The fungal strain Aspergillus clavatus MFD15 yielded the compound 1H-1,2,4 Triazole 3-carboxaldehyde 5-methyl, which exhibited antibacterial properties against Staphylococcus epidermidis and E. coli [47] with the MIC values of more than 500 μg/ml The strains showing MIC values exceeding 500 μg/ml indicated low efficacy.

Prenylated phenylbutyrolactone group compounds, namely aspulvinone R, S, T, isolated from the fungus Aspergillus flavipes KUFA1152 associated with the sponge Mycale sp. from Samasean Island, Gulf of Thailand, Chonburi Province. Aspulvinone R (8) and aspulvinone S (9) exhibit potential as novel drugs for their antibacterial activity against E. faecalis ATCC 29212, S. aureus ATCC 29213, E. faecalis B3/101 (VRE), and S. aureus 66/1 (MRSA) evidenced by their MIC values ranging from 4.0 to 16.0 μg/ml [48]. Aspergillus stellatus KUFA 2017 was also reported to be associated with the Mycale sp. The presence of 5[(3E,5E)-nona-3,5-dien-1-yl]-benzene (10) in the fungal extract has antibacterial activity against E. faecalis ATCC 29212, E. faecalis B3/101 (VRE), S. aureus ATCC 29213, and S. aureus 74/24 (MRSA) with MIC values ranging from 16.0 to 64.0 μg/ml. It also significantly inhibited nitric oxide production in lipopolysaccharide-induced raurine macrophage RAW264.7 cells and was found to contain antibiofilm activity [49].

Genus Penicillium

Penicillium has been widely acknowledged and proven as an antibiotic since its discovery by Fleming [50]. Research on this genus has continued to expand the understanding of its potential benefits on medication. Penicillium species provide a wide range of metabolite compounds and their biological activities either from terrestrial or marine environments [51]. Several publications regarding the antibacterial activity of the genus Penicillium fungi associated with sponges are listed in Table 1. Some studies summarized in this review did not isolate and identify the structure. Hence, which chemicals are involved in the pharmacological activity is still unclear, and additional investigation is required.

Table 2. Summary of research on sponge-associated fungi and their antibiofilm activity. [Click here to view]

The citrinin (11) was isolated from the fungus Penicillium sp. FF001 association with sponge Melophus sp., showing potent antibacterial activity against antibiotic-resistant bacteria, such as MRSA ATCC 10537, rifampicin-resistant S. aureus, and Vancomycin-resistant Enterococcus faecium [52]. Another potential of citrinin is antifungal activity against Cryptococcus neoformans (MIC 3.90 μg/ml) and cytotoxic to shrimp larvae (LD50 96 μg/ml [52]. Penicillium crysogenum also produces citrinin and shows potent antibacterial against gram-positive and Gram-negative bacteria, and antifungal activity [53,54]. The fungal strain Penicillium adametzioides AS-53 was cultivated using Potato Dextrose Agar, resulting in two novel bisthiodiketopiperazine compounds, namely adametizines A (12) and B (13). Concurrently, the metabolites isolated from cultivation in rice media showed novel acorane sesquiterpenes, namely adametacorenols A and B. Adametizines A potential were developed as a novel antibacterial activity based on the MIC values, which were less than 16 μg/ml against bacteria S. aureus, Aeromonas hydrophilia, Vibrio harveyi, Vibrio parahaemolyticus, and Gaeumannomyces graminis. Cl substitution in C-7 enhances the cytotoxic effect on shrimp larvae and their antimicrobial activity [55]. Quinazolin group compounds, including Lapatins B, glyantrypine, and verruculogen were also isolated from these fungi [56].

Two citrinin-derived compounds, namely Penicitrinone A (14), were isolated and identified from Suberea sp. and found to be inhibited by Mycobacterium smegmatic ATCC607 bacteria (MIC 32 μg/ml). In contrast, Penicitrinol J (15) indicated the MIC values 16, 16, and 32 μg/ml for B. subtilis JH642, Bacillus megaterium DSM32, M. smegmatic ATCC607 [57]. Based on the MIC values, all compounds were classified as moderate. The presence of phenolics in the structure of penicitrinol increases its potential as an antibacterial. Penicillium erubescens KUFA0220 associated with sponge Neopetrosia sp. contains several metabolites including GKK1032B, citromycin, 12-methoxycitromycin, myxotrichin D, 12-methoxycitromycetin, anhydrofulvic acid, myxotrichin C, penialidin D, penialidin F, SPF-3059-30, and secalonic acid A. Only the GKK1032B demonstrated the potential to serve as bacteriostatic against E. faecalis ATCC 29212 vancomycin-resistant E. faecalis (VRE) B3/101, E. faecium ATCC 19434, and E. faecium 1/6/63 (VRE) with the MIC values between 8 and 16 mg/ml. A novel polyketide, namely erubescensoic acid, was also isolated from this fungus. The compound was also tested for inhibiting bacterial growth against Gram-negative, Gram-positive, and MDR strains from the environment. The results showed that this compound had no activity. This compound was also unable to inhibit biofilm formation against P. aeruginosa ATCC 27853, S. aureus ATCC 29213, E. faecalis ATCC 29212 (Table 2) [58,59].

Sponge-associated fungi as a source of antibiofilm

Superbugs have become a global health issue and contribute to morbidity and mortality rates. Superbugs are described by the increased immunity of microbes to several types of antibiotics. It may occur naturally in bacteria when their genes evolve. Another reason for increasing resistance is biofilm formation, which makes treating infectious diseases more difficult, and thus makes it necessary to develop strategies to eradicate superbugs effectively [97–100]. Biofilm is microorganism communities that adhere to the surface and form an extracellular matrix known as extracellular polymeric substance (EPS) consisting of polysaccharides, various proteins, lipids, and DNA [101–103, 1]. Biofilm morphology depends on its constituent bacteria and conditions for biofilm formation.

The cycle growth of biofilm formation begins with the initial attachment phases. Planktonic bacteria attached to a surface or devices initiate reversible or irreversible attachment. Microorganisms have specific signals to start biofilm formation. They prefer hydrophobic surfaces because they reduce the repulsive force between the bacteria and the surface, resulting in stronger adhesion. The next phase is microcolony formation, characterized by bacteria multiplying and biofilm EPSs production [2,104–106]. In the mature phase, biofilms develop entirely and, eventually multilayers. The cell density reaches a peak and forms a typical 3-D biofilm structure. After the biofilm reaches complete maturity, the dispersal step begins by releasing bacteria into the environment. The dispersal stage is essential in the biofilm life cycle because it promotes new biofilm initiation at other sites [1,107]. The biofilm life cycle is presented in Figure 5. In recent years, biofilm-related research has attracted many researchers, although studies on exploring marine-associated fungi and their potential as antibiofilm are still rare. The summarized data of sponge-derived fungi and their potential to serve as antibiofilm is shown in Table 2. A cis-cyclo (Leucyl-Tyro-syl) dipeptide was successfully isolated from Penicillium sp. associated with the sponge Axinella corrugata. The compound effectively inhibited biofilm formation of S. epidermidis ATCC 35984 up to 85% at a concentration of 1 mg/ml and fully inhibited at 2 mg/ml. Observation of the biofilm structure by Scanning Electron Microscope (SEM) showed that the sample group treated with 1.0 mg ml dipeptide showed less intense EPS formation [108]. Diketopiperazines have many biological activities, such as antitumor and antiviral. Bacterial signaling systems, including quorum-sensing (QS), can be influenced by diketopiperazine [109,110]. Secalonic acid D (SAD) and B isolated from Penicillium sp. SCSGAF 0023 effectively inhibits biofilm formation >90% at 6.25 μg/ml against S. aureus ATCC 6538, although there is no effect on the P. aeruginosa PAO1 on the concentration up 100%. SAD showed a biofilm eradication effect at level 12.5 μg/ml. The biofilm architecture of S. aureus, also influenced by SAD, showed a decrease in biofilm biomass and thickness by the dose-dependent. SAD can regulate the transcription level of biofilm-related genes. Nonetheless, other genetic studies are needed to clarify the mechanism of SAD inhibition of S. aureus biofilm formation [111], which concludes that SAD has the potential to develop as an antibiofilm agent.

Figure 4. Structure compounds from marine sponge derived-fungi with potent antibacterial activity [33,34,70,76,80,81,83,65,72,39,43,49,52,55,57,62,65]. [Click here to view]

Tenellic acid C and neospinosic acid, both isolated from N. spinosa KUFA 1047, are potentially developed as antibiofilm agents due to their ability to suppress biofilm production of E. coli ATCC 25922 and S. aureus ATCC 29213. Neospinosic acid particularly showed the most potent inhibition, up to 44% for S. aureus ATCC 29213 biofilm formation (Table 2), and the viability of biofilm decreased by 98% after 8 hours of incubation, even though after 24 hours, the decrease in viability was only 10%. This phenomenon may occur because bacteria adapt genetically and phenotypically [65]. The prenylated phenylbutyrolactones, identified as Aspulvinones B’, Aspulvinones H, Aspulvinones R, Aspulvinones S, and Aspulvinones T isolated from A. flavipes KUFA1152 showed antibiofilm activity to E. faecalis ATCC 29212 and S. aureus ATCC 29213 bacteria (Table 2). The presence of prenyl substituents in ring A of compounds Aspulvinones R and Aspulvinones S may be responsible for antibacterial activity and inhibition of biofilm formation. Nevertheless, none of the compounds exhibited synergistic effects with antibiotics against multidrug-resistant bacteria.

Another strain was isolated from Mycale sp, A. stellatus KUFA 2017, contains 5[(3E,5E)-nona-3,5-dien-1-yl]benzene can inhibit biofilm formation almost 99% on E. faecalis ATCC 29212 and S. aureus ATCC 2921 [48,49] (Table 2). These compounds may develop as new drugs for antibacterial and biofilm inhibitors. Several compounds isolated from fungi associated with marine sponges may not show antibiofilm activities, such as erubescenoic acid (Table 2), which was isolated from P. erubescens KUFA0220 [58,59]. However, it does not mean they have no biological effects, thus making it crucial to conduct further investigation in other bioassays to examine what these compounds can potentially accomplish. Biofilms are formed not only of monospecies but also of polymicrobial (including Gram-positive and Gram-negative bacteria) or biofilm complexes of bacteria and fungi. Each Gram-positive or Gram-negative bacteria has its mechanism for biofilm formation [112], but generally, the stages of biofilm formation are illustrated in Figure 5. Staphylococcus aureus is a Gram-positive bacteria contributing to most biofilm-associated infections, including biofilm on medical devices. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 are Gram-negative bacteria that produce strong biofilms [113–115].

Figure 5. Biofilm life cycle. [Click here to view]

Biofilm formation is a complicated process, and improving our understanding of biofilms molecular composition and function will greatly assist in identifying and developing effective strategies for preventing and treating infections caused by these complex multicellular communities. Several feasible strategies are applicable for biofilm prevention and therapy, including biofilm formation inhibition and eradicating existing biofilms. Inhibition of biofilm formation by preventing bacteria from attaching to a surface and inhibiting the formation of EPS [101] inhibits cell-to-cell communication by anti-QS [116], modify surfaces to make it harder for bacteria to attach and grow on surfaces, especially on medical devices [117,118]. Physical and chemical methods also can eradicate biofilm [119–121].

This review highlighted that some compounds isolated from sponge-associated fungi showed antibacterial and antibiofilm activity, but some were only active as antibacterial or antibiofilm. This phenomenon may occur because the mechanism of action of antibiofilm may differ from that of antibacterials, especially if polymicrobials cause biofilms. Some studies did not report the compound mechanism as antibacterial or antibiofilm. Future research is expected to observe the compound mechanism thoroughly and may lead to the development of antibiofilm agents for specific targets.

CONCLUSION

Currently, the efficacy of conventional antibiotics is especially limited to biofilm-related infections. The marine environment offers a rich opportunity to discover novel, highly effective antibacterial, and antibiofilm chemicals. This review summarized the isolated compounds from marine derive-fungi with promising potential to develop as antibacterial or antibiofilm, including anthraquinones, sterigmatocystin analog, hydroxy pyrrolidine alkaloids, helvolic acid derivatives, lactones, prenylated phenylbutyrolactones, citrinin and derivatives, bisthiodiketopiperazine, cyclotetrapeptides, dihydrochromone dimer, amino lipopeptide, furan derivatives, aspiron-derivatives, halogenated metabolites, and alkaloids. Thorough research is required to determine the reliable mechanism of bioactive compounds, considering that the interaction between bacteria in biofilms is challenging to treat. Hence, exploring new antibacterial and antibiofilm agents derived from marine natural products has considerable value to drug development as a way to solve problems related to sponge availability.

ACKNOWLEDGMENTS

The author would like to acknowledge to the Center For Higher Education Funding and Indonesia Endowment Fund for Education for their funding support as Doctoral Scholarship.

AUTHOR CONTRIBUTION

All authors contributed to the conception and design, acquisition of data, analysis, and interpretation of data, drafting the article, or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the published version; and agreed to be accountable for all aspects of the work. According to the guidelines defined by the International Committee of Medical Journal Editors (ICMJEs), all authors are eligible to be authors.

CONFLICTS OF INTEREST

The authors declare that there is no conflict of interest.

ETHICAL APPROVALS

This study does not involve animal or human subjects for experimental purposes.

DATA AVAILABILITY

All data generated and analyzed are included in this research article.

PUBLISHER’S NOTE

This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.

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