A Jordanian research team has added a potential weapon to combat antibiotic-resistant superbugs, after proving the ability of compounds extracted from a rare type of marine sponge to kill dangerous bacterial strains, including methicillin-resistant Staphylococcus aureus bacteria.
Research teams around the world are searching for new pharmaceutical compounds to provide solutions to this problem, which the World Health Organization describes as a “silent pandemic,” and the Jordanian contribution came through a type of marine sponge in the Gulf of Aqaba, which is “Dactylosspongia elegans.”
During the study published in the journal “Biomedical Reports,” the research team from the University of Jordan collected three types of marine sponges, “Stellita,” “Axinella,” and “Dactylospongia elegans,” from depths ranging between 345 and 362 meters in the Gulf of Aqaba, which is one of the deepest and least explored marine environments in the region. Then they extracted their chemical compounds using ethanol and tested their effect against six types of bacteria, which included positive bacteria. Gram and Gram-negative bacteria, in addition to the methicillin-resistant Staphylococcus aureus strain.
The results showed that only one species, Dactylospongia elegans, had extracts that showed strong and clear activity against Gram-positive bacteria. Most importantly, the researchers measured what is known as the “minimum inhibitory concentration” and the “minimum lethal concentration” and found that the extract was able to stop the growth of bacteria at a concentration of 1 mg/ml, and kill them completely at 2 mg/ml, which are indicators that reflect strong biological effectiveness, especially against resistant strains.
40 vital compounds…the secret of effectiveness
The next step after discovering the power of the Dactylospongia elegans sponge extract was to understand the secret of this power. For this task, scientists used the “liquid chromatography coupled with mass spectrometry” technique to analyze its chemical composition, discovering the presence of about 40 diverse biological compounds, including compounds known for their antibacterial ability such as phenolic acids (gallic and caffeic), along with quinone compounds (polinaquinone and dactyloquinone), and an alkaloid compound. A marine complex called (Manzamine A).
Regarding the secret of this particular sponge having antibacterial activity, Dr. says: Mamoun Al-Rashidat, head of the Molecular and Microbial Ecology Laboratory at the Department of Biological Sciences at the University of Jordan and the main researcher of the study, said in statements to Al Jazeera Net that this is due to the specificity of its complex biological and environmental environment.
He explains that the samples were collected from a highly biodiverse deep coral reef environment, where sponges live in close interaction with coral reefs and are subject to high microbial and chemical competitive pressures. These complex environmental conditions contribute to the formation of a distinct microbial community inside the sponge known as (holobiont), which is directly reflected in the nature and quality of the chemical compounds it produces.
The conditions of the depths in the Gulf of Aqaba, including the stability of a warm water column at about 21 degrees Celsius across the depths, coupled with low lighting, scarcity of nutrients, and high hydrostatic pressure, create a unique ecosystem that enhances microbial interactions and chemical defenses among organisms.
He adds, “These environmental pressures lead to the activation of pathways for the production of vital secondary compounds, which raises the levels of some active chemical classes such as quinones, phenolic acids, and the complex marine alkaloid compound (manzamine A). This chemical variation is the decisive factor behind the ability of the Dactylosspongia elegans sponge alone to show clear inhibition of Gram-positive bacteria.”
How are gram-positive bacteria targeted?
Phenolic acids (gallic and caffeic) weaken the integrity of the cell membrane and disrupt the formation of biofilms, while quinones (polinaquinone and dactyloquinone) create oxidative stress within cells by generating reactive oxygen species, while manzamine A inhibits the protein synthesis process inside the bacterial cell.
Mamoun says, “These mechanisms mainly target Gram-positive bacteria, which have a thick cell wall layer but lack a protective outer membrane. As for Gram-negative bacteria, they have an outer membrane rich in glycolipid compounds that acts as an effective barrier that prevents the penetration of many active compounds, thus limiting the effect of these substances on them.”
He added: “Accordingly, these compounds are not broad-spectrum antibiotics, but rather specialized molecules that work on specific cellular targets, which makes their effectiveness more selective, and reduces their ability to affect Gram-negative bacteria without making structural or chemical modifications to them.”
Moving from the laboratory to manufacturing
In order for the transition from initial laboratory results to the stage of developing a potential drug to occur, there are a set of complex scientific and technical challenges, which Mamoun points out.
At the forefront of the challenges is the step of isolating effective compounds and accurately determining their chemical structures, in addition to understanding their mechanisms of action and the relationship between chemical structure and biological activity. It also remains necessary to determine whether the antibacterial effect results from one main compound, or from a synergy between several compounds that work together to enhance effectiveness.
The next stage concerns biological verification, which includes toxicity testing on human or animal cells, then conducting drug safety studies in appropriate animal models to ensure that these compounds are effective and safe at the same time.
Another fundamental challenge is sustainable supply and production, as the compounds extracted from marine sponges are often in very small quantities, which makes relying on natural collection impractical and environmentally unsustainable. Therefore, research is moving towards alternatives such as cultivating sponges, studying the microbes associated with them, using genomic techniques, or chemical and semi-chemical synthesis of these compounds.
Mamoun says: “In the near term, the most realistic approach is to reproduce active compounds in vitro based on knowledge of their spectral and structural data, ensuring their transformation into a scalable and sustainable pharmaceutical platform.”
