Microbial biofilms contribute to severe global health threats by fostering chronic infections and antibiotic resistance. With limited drugs available that specifically target microbial biofilms, the scientific community stands before an imperative challenge to develop innovative therapeutic strategies. A recent review illuminates the potential of small molecules and nanoparticles in subverting these tenacious biofilm fortresses, signaling a new horizon in medical intervention.
The insidious nature of microbial biofilms has been a relentless challenge in the field of medicine. Biofilms—clusters of microorganisms encased within a self-produced polymeric matrix—afford pathogens robust protection against conventional antibiotics and the host’s immune defense, culminating in persistent infections that can be lethal. This resistance fortress is not an issue to be taken lightly; it signifies an ever-increasing threat to global health and demands urgent attention and action. Today marks a significant leap in the continuous battle against microbial biofilms, as a research review sheds light on hopeful advancements that might well alter the course of therapeutic interventions.
Published in the ‘Microbial Pathogenesis’ journal, the review article titled “Role of small molecules and nanoparticles in effective inhibition of microbial biofilms: A ray of hope in combating microbial resistance” bears the Digital Object Identifier (DOI) 10.1016/j.micpath.2024.106543. It constitutes an unprecedented examination of nearly seventy-five distinct molecular scaffolds identified over the past decade (2010-2023), all presenting promising biofilm inhibition capabilities.
Authored by Gattu Rohith, Ramesh Sanjay S, and Ramesh Suhas S from the Postgraduate Department of Chemistry at JSS College of Arts, Commerce and Science—a Recognized Research Centre of the University of Mysore in Karnataka, India—this review categorizes the molecular scaffolds into five distinct sub-groups based upon their origin and design (excluding peptides): heterocycles, inorganic small molecules & metal complexes, small molecules decorated nanoparticles, small molecules derived from natural products, and small molecules designed via in-silico approach.
Notably, the use of small molecules derived from both plant and marine sources illustrates the integration of traditional knowledge with state-of-the-art technology. In contrast, in-silico designed small molecules illuminate the combined power of computational models and biological insights in advancing therapeutic interventions.
Heterocyclic compounds have captured researchers’ interest due to their structural complexity and capacity to interfere with microbial communication systems, such as quorum sensing, which are critical for the formation and maintenance of biofilms. By disrupting these pathways, heterocyclic compounds can inhibit biofilm formation or destabilize existing biofilms, making them vulnerable to treatment.
Inorganic small molecules and metal complexes offer a distinct approach to biofilm control. These substances can destabilize the biofilm matrix and exert antimicrobial effects, sometimes by generating reactive oxygen species or interfering with metal-ion homeostasis within microbial cells. Their unique modes of action can provide a valuable addition to the anti-biofilm arsenal.
Small molecules decorated on the surface of nanoparticles can target biofilms with precision and efficiency. These nanoparticles can penetrate the dense matrix and deliver bioactive agents directly to the cells, diminishing the protective barriers and allowing for enhanced antimicrobial activity at significantly lower doses, thus reducing potentially harmful side effects.
Natural products have historically been a bountiful source for drug discovery. Molecules isolated from plants and marine organisms have demonstrated promising antibiofilm activities. These compounds often possess complex structures that can disrupt various stages of biofilm development and can inspire the synthesis of new classes of antibiofilm agents.
In-silico methods leverage computational power to design molecules with specific characteristics tailored to target biofilms. By simulating and predicting how these molecules might interact with biological targets, researchers can streamline the discovery process and focus experimental efforts on the most promising candidates.
The authors unambiguously assert that their review serves as a comprehensive resource for future research endeavors aimed at developing new molecular entities to tackle the critical issue of antimicrobial resistance, primarily caused by biofilms. Recognizing the seriousness of the issue at hand, the declaration of no competing interest makes it evident that the authors’ motivation is purely scientific and rooted in the collective pursuit of enhanced public health.
References
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Keywords
1. Microbial biofilms
2. Antibiotic resistance
3. Small molecule inhibitors
4. Nanoparticle therapy
5. Biofilm disruption technology