The global crisis of antimicrobial resistance (AMR) is escalating due to the misuse and overuse of antibiotics, the slow development of new therapies, and the rise of multidrug-resistant (MDR) infections. Traditional antibiotic treatments face limitations, including the development of resistance, disruption of the microbiota, adverse side effects, and environmental impact, emphasizing the urgent need for innovative alternative antibacterial strategies. This review critically examines naturally derived biopolymers with intrinsic (essential feature) antibacterial properties as a sustainable, next-generation alternative to traditional antibiotics. These biopolymers may address bacterial resistance uniquely by disrupting bacterial membranes rather than cellular functions, potentially reducing microbiota interference. Through a comparative analysis of the mechanisms and applications of antibiotics and antibacterial naturally derived biopolymers, this review highlights the potential of such biopolymers to address AMR while supporting human and environmental health.
The World Health Organization (WHO) estimates that antimicrobial resistance (AMR) could cause up to 10 million deaths annually by 2050, with a severe impact on global healthcare costs and economic stability. Bacterial infections are among the most life-threatening healthcare challenges, accounting for approximately 13.6% of global mortality and affecting 1 in 8 individuals worldwide. The rise of multidrug-resistant (MDR) bacteria further highlights an urgent need for alternative, next-generation antibacterial treatments. While antibiotics have historically revolutionized healthcare, their widespread use has led to substantial challenges, including disrupting human microbiota and the rise of antibiotic-resistant bacterial strains.
Beyond their pathogenic roles, bacteria are integral to human health, especially in the gut, contributing to immune modulation and digestion. Consequently, the modern healthcare system cannot fully eliminate infection risk, particularly in post-surgical settings and procedures involving biomaterials or medical devices. Infections occur when infectious agents enter human body tissues, multiply, and trigger host immune responses. Although infections cannot be entirely prevented due to inevitable interactions with environmental microbes, targeted measures can mitigate bacterial invasion and inhibit replication at potential infection sites.
The human microbiome, especially the gut microbiota, comprises numerous symbiotic bacterial species (e.g., Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminococcus) that collectively represent approximately 90% of the gut flora. These beneficial microorganisms are crucial in digestion, nutrient absorption, and immune defense. Importantly, they maintain a delicate balance, contributing to immune regulation and protecting against pathogens without causing harm to the host. However, the broad-spectrum use of antibiotics has disrupted this balance, weakening the microbiota’s natural protective functions and impairing the immune response, leading to gut dysbiosis—an environment conducive to antibiotic-resistant strains.
While antibiotics effectively eliminate harmful pathogens, their indiscriminate targeting also affects beneficial bacteria, reducing microbial diversity and increasing the likelihood of antibiotic resistance. Inappropriate antibiotic use across sectors, including clinical and animal health, has further escalated the global antibiotic resistance crisis, contributing to the emergence of MDR pathogens that resist multiple antibiotic classes.
The decreasing efficacy of antibiotics and the limited availability of alternative treatments underscore the urgent need for new classes of antibacterial therapeutics. Ideal alternatives would incorporate mechanisms of action that lower the risk of resistance. In this context, naturally derived biopolymers (NDBs) have attracted significant attention due to their unique antibacterial properties. Although long used in biomedical applications, interest in biopolymers as antibacterial agents has surged, with publications on their use rising by approximately 400% since 2015.
Approximately two decades ago, antibacterial biopolymers, e.g., those with intrinsic antibacterial activity, were first proposed as alternatives to antibiotics for treating bacterial infections. Today, biopolymer-based strategies show potential for localized, non-antibiotic antibacterial applications that support the immune system and minimize impact on the natural microbiota. Such approaches could represent a sustainable innovation within modern healthcare.
Notably, NDBs disrupt bacterial membranes instead of targeting specific metabolic pathways, a mechanism less prone to resistance development. Numerous studies have documented the use of NDBs in biomedical devices, including drug delivery systems, contact lenses, and injectable cement, where they exhibit potent antibacterial activity and biocompatibility. This review provides a comprehensive examination of the potential of antibacterial NDBs, analyzing recent literature to compare their effectiveness and applications with those of conventional antibiotics. By exploring the mechanisms, advantages, and limitations of NDBs, this review assesses whether these biopolymers could serve as reliable, antibiotic-free therapeutics capable of complementing or partially replacing traditional antibiotics in treating bacterial infections—or whether their promise remains largely theoretical.
In the pre-antibiotic era, more than half of deaths were attributable to infections. Since the 20th century, antibiotics have revolutionized antibacterial therapeutics in the history of medicine, drastically changing modern medicine and extending the average human lifespan. Several groups and generations of antibiotics have been discovered and developed with specific target mechanisms of action on bacterial cells. Conventionally, antibiotics are classified as cell wall inhibitors, protein synthesis inhibitors, nucleic acid synthesis inhibitors, antimetabolites, and cytoplasmic membrane inhibitors.
