Antibiotics are medications that treat bacterial infections. Their discovery in the 20th century, notably penicillin, transformed medicine by providing effective treatments for once-fatal diseases, reducing mortality and extending lifespans. These drugs work by targeting and disrupting specific processes in bacteria, such as cell wall formation or protein synthesis, without harming human cells. Finding new antibiotics remains important for addressing ongoing and emerging bacterial threats to human health.
The Urgent Need for Novel Antibiotics
A significant challenge is increasing antibiotic resistance, where bacteria evolve to withstand antibiotics. This evolution is a natural process, but widespread antibiotic use has accelerated it, leading to bacteria that are harder to treat. Bacteria can develop resistance through genetic mutations or by acquiring resistance genes from other bacteria through horizontal gene transfer.
The implications of this resistance for public health are significant. Infections caused by resistant bacteria, often termed “superbugs,” become more difficult to manage, requiring longer hospital stays and sometimes leading to higher mortality rates. Examples include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and multidrug-resistant Mycobacterium tuberculosis. The current arsenal of effective antibiotics is diminishing, making new drug discovery a critical global health need.
How New Antibiotics Are Found
The search for new antibiotic compounds traditionally began with screening natural sources. Soil microbes have historically been a rich source, yielding many main classes of antibiotics, such as streptomycin from actinomycetes. Plants and marine organisms are also explored, with marine environments offering largely untapped potential due to their unique microbial diversity.
Modern approaches leverage advanced technologies to identify new antibiotic compounds. High-throughput screening (HTS) allows researchers to rapidly test vast libraries of molecules for antibacterial activity to identify promising candidates. Synthetic chemistry involves modifying existing antibiotic structures to create new compounds with improved properties or to overcome resistance mechanisms. Genomics and bioinformatics analyze bacterial genomes to identify new drug targets or undiscovered biosynthetic pathways that could produce novel antimicrobial compounds.
Beyond Traditional Antibiotics: Novel Approaches
Beyond compounds that kill bacteria, innovative strategies combat bacterial infections. Bacteriophage therapy uses viruses, known as phages, that infect and destroy bacteria, offering a precise way to target pathogens. These phages can also make bacteria more sensitive to existing antibiotics.
Anti-virulence drugs disarm bacteria rather than kill them, preventing harm by inhibiting toxin production or biofilm formation. This approach may reduce selective pressure for bacteria to develop resistance, as their survival is not directly threatened. Antibiotic potentiators restore the effectiveness of older antibiotics against resistant bacterial strains, making previously ineffective drugs useful again.
CRISPR-based therapies use gene-editing technology to target and eliminate antibiotic resistance genes within bacteria. This involves delivering the CRISPR-Cas system into bacteria, often via phages, to cleave specific DNA sequences or remove resistance-encoding plasmids, which can lead to bacterial cell death or resensitize them to antibiotics. Host-directed therapies focus on boosting the body’s immune response to fight infections, rather than directly attacking bacteria.