Next-Generation Drug Targets for Fighting Multidrug-Resistant Bacteria: A Review

Ayasha Saiffi; Sanjar Alam; Devesh Kumar; Akshay Kumar; Mohit Kumar

doi:10.2174/0113816128406584251028160407

Next-Generation Drug Targets for Fighting Multidrug-Resistant Bacteria: A Review

Curr Pharm Des. 2026 Mar 18. doi: 10.2174/0113816128406584251028160407. Online ahead of print.

Authors

Ayasha Saiffi¹, Sanjar Alam¹, Devesh Kumar², Akshay Kumar³, Mohit Kumar⁴

Affiliations

¹ R.V. Northland Institute, Dadri, Greater Noida, U.P., 203207, India.
² Institute of Pharmaceutical Research, GLA University, District Mathura, U.P., Pincode, 281 406, India.
³ Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India.
⁴ Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.

PMID: 41937522
DOI: 10.2174/0113816128406584251028160407

Abstract

Introduction: The global rise in antibiotic resistance poses a serious threat to public health by undermining the effectiveness of standard antimicrobial therapies. The rapid rise of multidrug-resistant (MDR) bacterial strains has created an urgent demand for the identification of novel drug targets and the development of innovative therapeutic approaches.

Methodology: The methodology for this review was based on an extensive literature search using databases such as PubMed, Google Scholar, Scopus, and Web of Science, covering studies from 1998 to 2025. Articles focusing on novel drug targets, antimicrobial resistance mechanisms, and next-generation therapeutic strategies were screened and selected based on their scientific quality and contribution to the field. Data from clinical trial registries and reputable websites were also incorporated to provide comprehensive insights into emerging approaches against multidrug-resistant bacteria.

Results: The review identifies several promising approaches for combating MDR pathogens. These include targeting bacterial virulence factors, cell wall synthesis enzymes (Mur ligases, Lipid II, and C55-PP), and proteins that mediate resistance. Additionally, advanced drug delivery systems, such as liposomes, solid lipid nanoparticles, exosomes, and biomimetic carriers, enhance antibiotic bioavailability and site-specific action. Pharmacogenomic approaches further personalize treatment regimens, potentially improving outcomes and reducing the emergence of resistance.

Discussion: The review highlights that multidrug-resistant bacteria continue to pose a significant threat, necessitating the development of innovative therapeutic approaches. Although novel molecular targets and nanocarrier-based delivery systems offer substantial promise, their clinical translation is limited by challenges such as off-target effects, biological barriers to delivery, and regulatory hurdles. Overcoming these obstacles will require the integration of advanced technologies with pharmacogenomics and host-targeted therapeutic strategies.

Conclusion: Combating antibiotic resistance requires an integrated approach combining novel drug targets, advanced delivery systems, and tailored therapeutic approaches. Innovations in nanotechnology, immunotherapy, and pharmacogenomics offer viable solutions to this escalating crisis. Strategic interdisciplinary collaboration is critical for developing sustainable antimicrobial treatments and preserving the efficacy of existing antibiotics.

Keywords: Antimicrobial resistance; CRISPR-based therapeutics; antimicrobial peptides; multidrug-resistant bacteria; nanocarrier-based drug delivery.; novel drug targets.