Summary of Topic: This collection showcases innovative research into alternative antimicrobial therapies combating drug resistance by targeting pathogen-specific and host-directed metabolic pathways. Host-directed therapy (HDT) is explored for disrupting lipid metabolism pathways used by pathogens, emphasizing viability in managing resistant viral and bacterial infections. Pyrazinoic acid, derived from the tuberculosis antibiotic pyrazinamide, was proven to inhibit Mycobacterium tuberculosis by disrupting proton motive force and uncoupling oxidative phosphorylation, revealing clarifications regarding its mechanism of action. Targeting pathogens directly, researchers examined novel peptide inhibitors against Helicobacter pylori oxidative enzymes (Hp0231/DsbK), aiming to neutralize bacterial virulence without altering microbiota composition. Additionally, RNA methyltransferase (Rv3366) in M. tuberculosis was demonstrated as a promising drug target, with repurposed FDA-approved drugs (Levodopa and Droxidopa) identified as potential inhibitors. Lastly, engineered chimeric RNase proteins exhibit enhanced antimicrobial activities based on combining structural elements from different RNase variants—providing a novel protein-based antibacterial strategy. Together, these findings highlight next-generation therapeutic strategies essential against growing antimicrobial resistance, emphasizing host-directed approaches, enzyme-focused targeting, drug repurposing, and antimicrobial protein engineering.
The evolution and spread of antimicrobial resistance (AMR) has become a major threat to global health and healthcare systems, being the cause of at least 700 000 deaths/year worldwide, and this figure is estimated to reach 10 million by 2050 if no effective actions are taken. Moreover, the situation is likely to worsen as a consequence of the COVID-19 pandemic, for the extensive use of antimicrobials in COVID-19 cotreatment, as well as treatment interruptions or slowing down of monitoring programs due to lockdown measures. Very likely, the misuse and overuse of antimicrobial agents in healthcare settings, agriculture, and livestock represent the main cause of AMR diffusion. Therefore, the fight against AMR needs different approaches, including improvements in the management of antibiotics, but also the development of new antimicrobials or vaccines, as well as the use of alternative strategies.
The urgent necessity for new and improved antimicrobial drugs implicates the need for new targets and novel molecular structures to overcome cross-resistance. The aim of this Research Topic is to collect the recent advances in the investigation of potential enzymatic targets, involved not only in essential metabolic pathways (i.e., central metabolism, cell division machinery, cell wall synthesis, etc.), but also in pathways fundamental in establishing and maintaining the infection (i.e., virulence factors, quorum sensing, biofilm synthesis, etc.).
The issue of AMR leads to the need of developing novel antimicrobials possibly against new targets. For this reason, it is necessary not only to move towards a common objective of the appropriate use, but also to promote the research for the development of new antimicrobials against novel targets, or the use of alternative strategies such as anti-virulence approaches, which prevent microbial pathogenesis without killing an infectious agent.
This Research Topic invites original research as well as review articles concerning all aspects of investigation of enzymatic targets for novel antimicrobials. We are particularly interested in research exploring:
- Antimicrobial resistance
- Drug discovery and development
- Drug design and in-silico approaches
- Anti-microbial targets
- Anti-virulence targets
- Target-based high-throughput screening
Summary of Topic: This collection showcases innovative research into alternative antimicrobial therapies combating drug resistance by targeting pathogen-specific and host-directed metabolic pathways. Host-directed therapy (HDT) is explored for disrupting lipid metabolism pathways used by pathogens, emphasizing viability in managing resistant viral and bacterial infections. Pyrazinoic acid, derived from the tuberculosis antibiotic pyrazinamide, was proven to inhibit Mycobacterium tuberculosis by disrupting proton motive force and uncoupling oxidative phosphorylation, revealing clarifications regarding its mechanism of action. Targeting pathogens directly, researchers examined novel peptide inhibitors against Helicobacter pylori oxidative enzymes (Hp0231/DsbK), aiming to neutralize bacterial virulence without altering microbiota composition. Additionally, RNA methyltransferase (Rv3366) in M. tuberculosis was demonstrated as a promising drug target, with repurposed FDA-approved drugs (Levodopa and Droxidopa) identified as potential inhibitors. Lastly, engineered chimeric RNase proteins exhibit enhanced antimicrobial activities based on combining structural elements from different RNase variants—providing a novel protein-based antibacterial strategy. Together, these findings highlight next-generation therapeutic strategies essential against growing antimicrobial resistance, emphasizing host-directed approaches, enzyme-focused targeting, drug repurposing, and antimicrobial protein engineering.
The evolution and spread of antimicrobial resistance (AMR) has become a major threat to global health and healthcare systems, being the cause of at least 700 000 deaths/year worldwide, and this figure is estimated to reach 10 million by 2050 if no effective actions are taken. Moreover, the situation is likely to worsen as a consequence of the COVID-19 pandemic, for the extensive use of antimicrobials in COVID-19 cotreatment, as well as treatment interruptions or slowing down of monitoring programs due to lockdown measures. Very likely, the misuse and overuse of antimicrobial agents in healthcare settings, agriculture, and livestock represent the main cause of AMR diffusion. Therefore, the fight against AMR needs different approaches, including improvements in the management of antibiotics, but also the development of new antimicrobials or vaccines, as well as the use of alternative strategies.
The urgent necessity for new and improved antimicrobial drugs implicates the need for new targets and novel molecular structures to overcome cross-resistance. The aim of this Research Topic is to collect the recent advances in the investigation of potential enzymatic targets, involved not only in essential metabolic pathways (i.e., central metabolism, cell division machinery, cell wall synthesis, etc.), but also in pathways fundamental in establishing and maintaining the infection (i.e., virulence factors, quorum sensing, biofilm synthesis, etc.).
The issue of AMR leads to the need of developing novel antimicrobials possibly against new targets. For this reason, it is necessary not only to move towards a common objective of the appropriate use, but also to promote the research for the development of new antimicrobials against novel targets, or the use of alternative strategies such as anti-virulence approaches, which prevent microbial pathogenesis without killing an infectious agent.
This Research Topic invites original research as well as review articles concerning all aspects of investigation of enzymatic targets for novel antimicrobials. We are particularly interested in research exploring:
- Antimicrobial resistance
- Drug discovery and development
- Drug design and in-silico approaches
- Anti-microbial targets
- Anti-virulence targets
- Target-based high-throughput screening
