Tuberculosis remains a significant concern in global public health due to its intricate biology and propensity for developing antibiotic resistance. Discovering new drugs is a protracted and expensive endeavor, often spanning over a decade and incurring costs in the billions. However, computer-aided drug design (CADD) has surfaced as a nimbler and more cost-effective alternative. CADD tools enable us to decipher the interactions between therapeutic targets and novel drugs, making them invaluable in the quest for new tuberculosis treatments. In this review, the authors explore recent advancements in tuberculosis drug discovery enabled by in silico tools. The main objectives of this review article are to highlight emerging drug candidates identified through in silico methods and to provide an update on the therapeutic targets associated with Mycobacterium tuberculosis. These in silico methods have not only streamlined the drug discovery process but also opened up new horizons for finding novel drug candidates and repositioning existing ones. The continued advancements in these fields hold great promise for more efficient, ethical, and successful drug development in the future.
Latent tuberculosis infection (LTBI) represents a subclinical, asymptomatic mycobacterial state affecting approximately 25% of the global population. The substantial prevalence of LTBI, combined with the risk of progressing to active tuberculosis, underscores its central role in the increasing incidence of tuberculosis (TB). Accurate identification and timely treatment are vital to contain and reduce the spread of the disease, forming a critical component of the global strategy known as “End TB.” This review aims to examine and highlight the most recent scientific evidence related to new diagnostic approaches and emerging therapeutic treatments for LTBI. While prevalent diagnostic methods include the tuberculin skin test (TST) and interferon gamma release assay (IGRA), WHO’s approval of two specific IGRAs for Mycobacterium tuberculosis (MTB) marked a significant advancement. However, the need for a specific test with global application viability has propelled research into diagnostic tests based on molecular diagnostics, pulmonary immunity, epigenetics, metabolomics, and a current focus on next-generation MTB antigen-based skin test (TBST). It is within these emerging methods that the potential for accurate distinction between LTBI and active TB has been demonstrated. Therapeutically, in addition to traditional first-line therapies, anti-LTBI drugs, anti-resistant TB drugs, and innovative candidates in preclinical and clinical stages are being explored. Although the advancements are promising, it is crucial to recognize that further research and clinical evidence are needed to solidify the effectiveness and safety of these new approaches, in addition to ensuring access to new drugs and diagnostic methods across all health centers. The fight against TB is evolving with the development of more precise diagnostic tools that differentiate the various stages of the infection and with more effective and targeted treatments. Once consolidated, current advancements have the potential to transform the prevention and treatment landscape of TB, reinforcing the global mission to eradicate this disease.
Gram-negative bacterial infections represent a critical global health threat due to rising antibiotic resistance, posing substantial clinical and economic burdens. The structural complexity of Gram-negative bacteria—including efflux pumps, enzymatic degradation mechanisms, genetic mutations, and altered membrane permeability, significantly complicates treatment with conventional antibiotics. Antimicrobial peptides (AMPs) offer great antimicrobial activity, rapid bactericidal effects, multiple mechanisms of action, and immune-modulatory properties. However, their clinical application is limited by enzymatic degradation, potential cytotoxicity, and high production costs. To address these limitations, advanced nanotechnology-based platforms, including lipid-based nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, are being explored as AMP delivery vehicles. These nanocarriers enhance peptide stability, bioavailability, targeted delivery, and therapeutic efficacy while reducing systemic toxicity. This review synthesizes recent advancements in AMPs and nanotechnology-based delivery systems, highlighting their combined potential to effectively combat multidrug-resistant Gram-negative pathogens.
The search for new antimicrobial agents is a continuous struggle, mainly because more and more cases of resistant strains are being reported. Mycobacterium tuberculosis (MTB) is the main microorganism responsible for millions of deaths worldwide. The development of new antimicrobial agents is generally aimed at finding strong interactions with one or more bacterial receptors. It has been proven that bacteriophages have the ability to adhere to specific and selective regions. However, their transport and administration must be carefully evaluated as an excess could prevent a positive response and the bacteriophages may be eliminated during their journey. With this in mind, the mycobacteriophage D29 was encapsulated in nanoliposomes, which made it possible to determine its antimicrobial activity during transport and its stability in the treatment of active and latent Mycobacterium tuberculosis. The antimicrobial activity, the cytotoxicity in macrophages and fibroblasts, as well as their infection and time–kill were evaluated. Phage nanoencapsulation showed efficient cell internalization to induce MTB clearance with values greater than 90%. Therefore, it was shown that nanotechnology is capable of assisting in the activity of degradation-sensitive compounds to achieve better therapy and evade the immune response against phages during treatment.
Gastrointestinal infections, which are caused primarily by pathogenic bacteria, remain a significant global health challenge. Their resilience is reinforced by various physical, biological, and biopharmaceutical barriers that complicate conventional therapeutic strategies. This review delves into the intricate landscape of managing these infections, addressing microbiota imbalances, the emergence of multidrug‐resistant strains, and the impact of dysbiosis and antibiotic overuse. Faced with these challenges, traditional therapies often fail, which is hindered by low bioavailability, prolonged regimens, and a growing risk of resistance. In this context, nanotechnology applied to antimicrobial peptides (AMPs) has emerged as a promising solution to enhance their stability and targeted delivery. Through a critical approach, diverse nanocarriers and their efficacy against intestinal pathogens are evaluated both in vitro and in vivo. This review advocates for intensified research on the encapsulation and functionalization of AMPs, envisioning their potential to redefine the control of intestinal infections on a global scale.
Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), remains a major global health concern, particularly due to the emergence of multidrug‐resistant and extensively drug‐resistant strains. The persistence and propagation of TB are favored by the pathogen's sophisticated virulence mechanisms, its ability to evade immune responses, and the formation of latent infections within granulomas. Current therapeutic regimens are limited by long treatment durations, drug resistance, and significant socioeconomic burdens. Antimicrobial peptides (AMPs) have emerged as promising alternatives because of their broad‐spectrum activity and reduced likelihood of resistance development. Nevertheless, their clinical application is hindered by rapid proteolytic degradation, low specificity and limited bioavailability. Recent advances in nanotechnology have facilitated the encapsulation and targeted delivery of AMPs, improving their therapeutic potential against TB. Furthermore, the integration of computational approaches—such as molecular docking and molecular dynamics (MD) simulations—has enabled the rational design and optimization of AMPs, expediting the discovery of novel anti‐TB agents. This review summarizes the pathogenesis and resistance mechanisms of Mtb , highlights the current landscape and limitations of AMP‐based therapies, and discusses the role of nanotechnology and in silico tools in the development of new treatment strategies for TB.