Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens

Abstract

Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies.

Keywords: antimicrobial resistance; drug repurposing/drug repositioning; high-throughput screening; host-directed therapy; intracellular bacterial pathogens; multidrug resistance.

Figure 1

Schematic representation of the most common process to repurpose drugs against intracellular pathogens, as well as the most common mechanisms of action.

Figure 2

Summary of the scientific results obtained from different sources (PubMed, conferences and colleagues). The search was narrowed to drugs repurposed against bacteria and subsequently to intracellular bacteria. Only about 1% of the articles on drug repurposing focused on intracellular pathogens. Exclusion criteria were based on the off-target effects, toxicity, or lack of tested activity.