Exploring Structure-Activity Relationships of Niclosamide-Based Colistin Potentiators in Colistin-Resistant Gram-Negative Bacteria.

Colistin is primarily used as a last resort antibiotic against highly resistant Gram-negative bacteria (GNB). Rising rates of colistin resistance, however, may limit future use of this agent. The anthelmintic drug niclosamide has been shown to enhance colistin activity in combination therapy, but a detailed structure-activity relationship (SAR) for niclosamide against GNB has yet to be studied.

A niclosamide-tobramycin hybrid adjuvant potentiates cefiderocol against .

There is an urgent need for new therapies to overcome antimicrobial resistance (AMR) especially against Gram-negative bacilli (GNB). Multicomponent therapy combining antibiotics with enhancer molecules known as adjuvants is an emerging strategy to combat AMR. We have previously reported tobramycin-based adjuvants which are able to potentiate various antibiotics.

Overcoming β-Lactam resistance in Pseudomonas aeruginosa using non-canonical tobramycin-based antibiotic adjuvants.

β-Lactam antibiotics have for long been a mainstay in antimicrobial chemotherapy. However, due to its ubiquitous usage, bacteria have evolved multiple concerted pathways to evade its actions, underscoring the complexity of resistance to this class of drug. Current strategies to mitigate this problem are geared towards developing inhibitors that can shield the β-lactam core from enzymatic hydrolysis.

Dilipid Ultrashort Tetrabasic Peptidomimetics Potentiate Novobiocin and Rifampicin Against Multidrug-Resistant Gram-Negative Bacteria.

The development of new antibacterial agents and therapeutic approaches is of high importance to address the global problem of antibiotic resistance. Although antimicrobial peptides are known to synergize with certain antibiotics, their clinical application is limited by their systemic toxicity, protease instability, and high production cost. To overcome these problems, nine dilipid ultrashort tetrabasic peptidomimetics (dUSTBPs) were prepared consisting of three basic amino acids separated by a molecular scaffold, bis(3-aminopropyl)glycine, and were ligated to two fatty acids.

Repurposed Antimicrobial Combination Therapy: Tobramycin-Ciprofloxacin Hybrid Augments Activity of the Anticancer Drug Mitomycin C Against Multidrug-Resistant Gram-Negative Bacteria.

The lack of therapeutic options to treat infections caused by multidrug-resistant (MDR) pathogens, especially Gram-negative bacteria, is apparent. Therefore, it is imperative to develop new strategies to address the problem of antimicrobial resistance. Repurposing non-antibiotic commercial drugs for antimicrobial therapy presents a viable option.

Amphiphilic nebramine-based hybrids Rescue legacy antibiotics from intrinsic resistance in multidrug-resistant Gram-negative bacilli.

The inability to discover novel class of antibacterial agents, especially against Gram-negative bacteria (GNB), compel us to consider a broader non-conventional approach to treat infections caused by multidrug-resistant (MDR) bacteria. One such approach is the use of adjuvants capable of revitalizing the activity of current existing antibiotics from resistant pathogens. Recently, our group reported a series of tobramycin (TOB)-based hybrid adjuvants that were able to potentiate multiple classes of legacy antibiotics against various MDR GNB.

Polybasic peptide-levofloxacin conjugates potentiate fluoroquinolones and other classes of antibiotics against multidrug-resistant Gram-negative bacteria.

To address the rising threat of multidrug-resistant (MDR) bacteria, new therapeutic strategies must be developed. Efficacious drug combinations consisting of existing antibiotics and enhancer biomolecules called adjuvants offers a viable strategy. We have previously reported antibiotic hybrids consisting of tobramycin appended to different fluoroquinolones that possess potential as stand-alone antimicrobials as well as adjuvants.

Dilipid ultrashort cationic lipopeptides as adjuvants for chloramphenicol and other conventional antibiotics against Gram-negative bacteria.

The necessity to develop therapeutic agents and strategies to abate the spread of antibiotic-resistant pathogens is prominent. Antimicrobial peptides (AMPs) provide scaffolds and inspiration for antibiotic development. As an AMP of shorter scaffold, eight dilipid ultrashort cationic lipopeptides (dUSCLs) were prepared consisting of only four amino acids and varying dilipids.