A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds
1College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China.
Abstract:
The rapid emergence of antibiotic resistance has caused serious threat to global health. The worldwide search for novel classes of antibiotics to combat multidrug-resistant (MDR) bacteria is barren since about half a century ago. One of the promising strategies to combat the MDR pathogens is the combinational therapy. For instance, trimethoprim and clavulanic acid are routinely used to enhance the efficacies of sulfonamides and β-lactam antibiotics in clinic, respectively. Nevertheless, such adjuvants are specific for certain classes of antibiotics. We hypothesized that the combinational treatments with antibiotic adjuvants targeting the bacterial membrane may potentiate other antibiotics against MDR Gram-negative pathogens. In our recent publication (Song et al., doi: 10.1038/s41564-020-0723-z), we demonstrate a short linear antibacterial peptide SLAP-S25, which potentiates multiple antibiotics with different modes of action against Gram-negative bacteria. The mechanism studies show that SLAP-S25 targets both lipopolysaccharide (LPS) in the outer membrane and phosphatidylglycerol (PG) in the inner membrane of Escherichia coli. The impaired bacterial membrane caused by SLAP-S25 promotes the intracellular accumulation of antibiotics in bacteria. Our results indicate that the bacterial membranes are promising targets for the discovery of new antibiotics or antibiotic adjuvants to combat MDR bacteria associated infections.
Insights
Antibiotic resistance is a global threat. A novel peptide, SLAP-S25, enhances multiple antibiotics against resistant Gram-negative bacteria by targeting their membranes, offering a new strategy against infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Antibiotic resistance poses a significant global health threat, with a lack of novel antibiotic classes discovered in decades.
- Combinational therapy is a promising strategy, but existing adjuvants are often antibiotic-specific.
Purpose of the Study:
- To investigate if targeting bacterial membranes with adjuvants can enhance antibiotic efficacy against multidrug-resistant (MDR) Gram-negative pathogens.
- To identify and characterize novel antibiotic adjuvants with broad-spectrum potentiation capabilities.
Main Methods:
- Demonstration of a short linear antibacterial peptide, SLAP-S25, for its ability to potentiate various antibiotics against Gram-negative bacteria.
- Mechanistic studies involving targeting of lipopolysaccharide (LPS) in the outer membrane and phosphatidylglycerol (PG) in the inner membrane of Escherichia coli.
Main Results:
- SLAP-S25 demonstrated potentiation of multiple antibiotics with different mechanisms of action against Gram-negative bacteria.
- SLAP-S25 targets both the outer and inner bacterial membranes, leading to impaired membrane integrity.
- The impaired bacterial membrane facilitates increased intracellular accumulation of antibiotics.
Conclusions:
- Bacterial membranes are viable targets for developing new antibiotics and adjuvants.
- SLAP-S25 represents a promising antibiotic adjuvant that enhances the activity of existing antibiotics against MDR Gram-negative bacteria.
- This approach offers a potential strategy to combat challenging MDR bacterial infections.
More Related Videos
13:47Opsono-Adherence Assay to Evaluate Functional Antibodies in Vaccine Development Against Bacillus anthracis and Other Encapsulated Pathogens
Published on: May 19, 2020
07:32Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus MRSA Infection
Published on: September 1, 2023
Related Concept Videos
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...
00:57Antibiotic Selection
01:28Antimicrobial Effectiveness