M. Vishnu Vachana1 and Rupasree Mukhopadhyay2
1 Department of Genetics and Biotechnology, Osmania University, Hyderabad.
2 Department of Genetics and Biotechnology, Telangana Mahila Viswavidyalayam, Koti, Hyderabad.
Corresponding author: Dr Rupasree Mukhopadhyay rupasree.ucw@gmail.com
Antibiotics are low-molecular weight chemical substances produced by some microorganisms. They inhibit the growth of or kill some other types of microorganisms. They are believed to offer some advantages to the producer organism over other microorganisms in competition for space and food in natural environments though many scientists are not convinced with this hypothesis. The discovery of antibiotics during the last century revolutionized the field of chemotherapy and gave us some distinct advantages over infectious microorganisms. Widespread use of sulphur drugs, penicillin, streptomycin, chloramphenicol, tetracyclines, erythromycin, INH, ampicillin, amoxicillin and many other antibiotics by the medical practitioners in the clinical management of infectious organisms was associated with a substantial increase in the life- span and also in a significant improvement in the quality of life. However, the achievement was short-lived because of the emergence of microbial strains, resistant to the therapeutically useful antibiotics. The problem has adversely affected the prospect of chemotherapy to a significant extent during the past few decades. Microbial resistance to antibiotics is a natural phenomenon that does not require exposure to the antibiotics. Antibiotic-resistance is known to be manifested by bacterial strains, isolated from some totally uninhabited places and even from some niches that were detached from the human civilization for millions of years. But indiscriminate and injudicious use of antibiotics is aggravating the problem further. The concept of “Antibiotic Paradox” (the more is the use, the more is the resistance) put forward by Professor Stuart B. Levy (1938-2019) is revealing in this context. Scientists warn that a situation may not be far ahead, when we will be pushed back to the pre-antibiotic era with virtually no antibiotic available for clinical management of the life-threatening infections.
Development of new antibiotics, active against the antibiotic-resistant organisms, appears to be the need of the hour to control the debilitating and life-threatening ailments. The antibacterial-antibiotics isolated from soil bacteria were widely used during the last 60-70 years and hence pathogenic bacteria have already evolved with mechanisms that can foil the attack of the existing antibiotics. Thus, screening of soil bacteria in search of new antibiotics do not appear to offer any long-lasting outcome and scientists are forced to tap some other sources in search of new antibiotics. One of the potential sources, the attention of the scientists is focused on for this purpose, comprises of the wide variety of marine bacteria. The oceans cover 71% of the earth surface and are one of the richest sources of biodiversity. The marine environment entails diverse organisms such as microbiota, flora, and fauna that have evolved with distinct physiological and morphological features, metabolic pathways and also defense mechanisms to survive in
the dynamic environment of the oceans. They produce various biochemical components and unique secondary metabolites consisting of novel chemical structures, properties and composition called marine natural products (MNPs). MNPs offer countless advantages in various fields of applied biotechnology with both economic and environmental benefits. A number of the MNPs possess anti-cancer, anti-tumour, antimicrobial and anti-inflammatory properties and thus have great potential as promising chemotherapeutic agents. The vast biodiversity of oceans remains mostly unexplored and many of the MNPs are left undiscovered.
The unique biodiversity of marine ecosystem and the variety of molecules with high bioactive compounds produced by aquatic organisms in comparison to terrestrial life-forms grabbed the attention of researchers to identify new antimicrobials from the marine sources. This accelerated the demand for the discovery of novel MNPs with unique chemical characteristics. By the end of 2022, more than 38,000 natural products have been identified, isolated, and characterized from marine environments which include diverse chemical compounds with antimicrobial properties (Carroll et al., 2024).
Some recent advances
Rapid developments in the techniques during the past few decades aided in isolating several novel marine derived antibiotics. In 2020, in an attempt to screen for new bioactive compounds from marine sources, a group of researchers discovered a new tetracene derivative, named mersaquinone from the marine Streptomyces sp. EG1 isolated from a sediment sample collected from the North Coast of the Mediterranean Sea of Egypt. It showed anti-bacterial activity against methicillin-resistant Staphylococcus aureus or MRSA (Kim et al., 2020). In 2021, the same group identified two new chlorinated benzopyrene derivatives, chlororesisto-flavins A and B from marine-derived Streptomyces sp. strain EG32 that also showed significant anti-bacterial activity against MRSA (Kim et al., 2021). In the same year, a Japanese group discovered new antibiotics named Sealutomicins from marine actinomycetes Nonomuraea sp. MM565M-173N2 (Igarashi et al., 2021). Five new p-terphenyls, named nocarterphenyls D−H were isolated from marine sediment associated Nocardiopsis sp. strain HDN154086. They were found to possess promising activity against multiple bacteria (Chang et al., 2021). Recently, a group from China discovered four new compounds, namely the streptoindoles A–D from actinomycete Streptomyces sp. ZZ1118. These compounds also were found to have antimicrobial activity against MRSA, Escherichia coli, and Candida albicans (Newaz et al., 2022). Sulfoxide containing bisabolane sesquiterpenoid aspersydosulfoxide A was another newly identified antimicrobial compound obtained from a marine-derived fungi Aspergillus sydowii LW09 in 2023 (Yang et al., 2023). All these novel antibiotics can help in combating the rapidly increasing multi-drug-resistant microorganisms. In view of the all out effort paid by the researchers it appears reasonable to expect some more new antibiotics with broad spectrum activity against the pathogens during the years to come.
References
1. Carroll, A. R., Copp, B. R., Grkovic, T., Keyzers, R. A and Prinsep, M. R. (2024). Marine natural products. Natural Product Reports, 41(2), 162-207.
2. Chang, Y., Che, Q., Xing, L., Ma, C., Han, Y., Zhu, T., ... & Li, D. (2021). Antibacterial p-terphenyl with a rare 2, 2′-bithiazole substructure and related compounds isolated from the marine-derived Actinomycete Nocardiopsis sp. HDN154086. Journal of Natural Products, 84(4), 1226-1231.
3. Igarashi, M., Sawa, R., Umekita, M., Hatano, M., Arisaka, R., Hayashi, C., Ishizaki, Y., Suzuki, M., & Kato, C. (2021). Sealutomicins, new enediyne antibiotics from the deep-sea actinomycete bNonomuraea sp. MM565M-173N2. The Journal of Antibiotics, 74(5), 291-299. https://doi.org/10.1038/s41429-020-00402-1
4. Kim, M. C., Cullum, R., Hebishy, A. M., Mohamed, H. A., Faraag, A. H., Salah, N. M., Abdelfattah, M. S., & Fenical, W. (2020). Mersaquinone, A New Tetracene Derivative from the Marine-Derived Streptomyces sp. EG1 Exhibiting Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). Antibiotics, 9(5), 252. https://doi.org/10.3390/antibiotics9050252
5. Kim, M. C., Li, Z., Cullum, R., Molinski, T. F., Eid, M. A. G., Hebishy, A. M., ... & Fenical, W. (2021). Chlororesistoflavins A and B, Chlorinated Benzopyrene Antibiotics Produced by the Marine-Derived Actinomycete Streptomyces sp. Strain EG32. Journal of Natural Products, 85(1), 270-275.
6. Newaz, A. W., Yong, K., Lian, X., & Zhang, Z. (2022). Streptoindoles A–D, novel antimicrobial indole alkaloids from the marine-associated actinomycete Streptomyces sp. ZZ1118. Tetrahedron, 104, 132598. https://doi.org/10.1016/j.tet.2021.132598
7. Yang, X., Yu, H., Ren, J., Cai, L., Xu, L., & Liu, L. (2023). Sulfoxide-Containing Bisabolane Sesquiterpenoids with Antimicrobial and Nematicidal Activities from the Marine-Derived Fungus Aspergillus sydowii LW09. Journal of Fungi, 9(3), 347. https://doi.org/10.3390/jof9030347