https://orcid.org/0000-0003-4369-1772
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ABSTRACT
Introduction
Pseudomonas aeruginosa (PA) is a Gram-negative bacterium that can cause a wide range of severe infections in immunocompromised patients. The most difficult challenge is due to its ability to rapidly develop multi drug-resistance. New strategies are urgently required to improve the outcome of patients with PA infections. The present patent review highlights the new molecules acting on different targets involved in the antibiotic resistance.
Area covered
This review offers an insight into new potential PA treatment disclosed in patent literature. From a broad search of documents claiming new PA inhibitors, we selected and summarized molecules that showed in vitro and in vivo activity against PA spp. in the period 2020 and 2023. We collected the search results basing on the targets explored.
Expert opinion
This review examined the main patented compounds published in the last three years, with regard to the structural novelty and the identification of innovative targets. The main areas of antibiotic resistance have been explored. The compounds are structurally unrelated to earlier antibiotics, characterized by a medium-high molecular weight and the presence of heterocycle rings. Peptides and antibodies have also been reported as potential alternatives to chemical treatment, hereby expanding the therapeutic possibilities in this field.
Article highlights
The rapidly escalating prevalence of antimicrobial resistance by Pseudomonas aeruginosa is a global concern.
Patented Pseudomonas aeruginosa inhibitors and their use, as described in reports made from 2020-2023, are discussed.
Different types of antimicrobial agents, such as small molecule inhibitors, therapeutic antibodies and peptides, and their combination with well-established antibiotics are examined.
The review illustrates the chemical structures of Pseudomonas aeruginosa inhibitors.
The efficacy, expressed as MIC or IC50 relative to the representative active compounds, is provided.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Abbreviations
| Acid N-Hydroxysuccinimide Diester | = | SIDEA |
| Antimicrobial peptides | = | AMPs |
| Antimicrobial resistant | = | AMR |
| Bacterioferritin | = | Bfr |
| Bovine Serum Albumin | = | BSA |
| Cationic Antimicrobial Peptides | = | CAMPs |
| Cystic Fibrosis | = | CF |
| Dissociation Constant | = | Ki |
| Efflux Pump Inhibitors | = | EPIs |
| Ferritin | = | Ftn |
| Half Maximal Inhibitory Concentration | = | IC50 |
| Human Serum Albumin | = | HSA |
| Lipopolysaccharides | = | LPS |
| Minimum Inhibitory Concentration | = | MIC |
| Monoclonal Antibodies | = | mAbs |
| Mouse Liver Microsomes | = | MLM |
| Multidrug Resistance | = | MDR |
| Nitric Oxide | = | NO |
| Non‐cystic fibrosis bronchiectasis | = | NCFB |
| Outer Membrane Factor | = | OMF |
| Outer Membrane Proteins | = | OMPS |
| Outer Membrane | = | OM |
| p-nitro-phenyl-b-galactoside | = | pNO2-Ph-b-Gal |
| Polysaccharide | = | PS |
| Post-Antibiotic Effect | = | PAE |
| Pseudomonas Aeruginosa | = | PA |
| Pseudomonas Elastase | = | LASB |
| Quorum sensing | = | QS |
| Recombinant Diphtheria Toxoid | = | CRMl97 |
| Resistance Nodulation and cell Division | = | RND |
| Structure-Activity Relationship | = | SAR |
| Tetanus Toxoid | = | TT |
| Transpeptidases/Penicillin-Binding Proteins | = | PBPs |
| UDP-3-O-Acyl-N-Acetylglucosamine Deacetylase | = | LpxC |
| World Health Organization | = | WHO |
| Zinc-Binding Group | = | ZBG |
| α-Methyl-d-Galactoside | = | Me-α-Gal |
| β-Barrel Assembly Machinery | = | BAM |
Authors contributions
B. De Filippis and A. Ammazzalorso searched for the literature. A. Granese filtered the search results. All the authors analyzed the data. B. De Filippis wrote the manuscript. A. Ammazzalorso revised the final manuscript. All the authors read and approved the final version of the manuscript.