Discovery of Sortase A covalent inhibitors with benzofuranene cyanide structures as potential antibacterial agents against Staphylococcus aureus

New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase,CHAPK, as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. PurifiedCHAPKapplied to biofilms ofStaphylococcus aureusDPC5246 completely eliminated the staphylococcal biofilms within 4 h. In addition,CHAPKwas able to prevent biofilm formation by this strain. TheCHAPKlysin also reducedS. aureusin a skin decolonization model. Our data demonstrates the potential ofCHAPKas a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors.

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Covalent Sortase A Inhibitor ML346 Prevents Staphylococcus aureus Infection of Galleria mellonella

RSC Medicinal Chemistry ◽

10.1039/d1md00316j ◽

2021 ◽

Author(s):

Xiang-Na Guan ◽

Tao Zhang ◽

Teng Yang ◽

Ze Dong ◽

Song Yang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cell Wall ◽

Galleria Mellonella ◽

Surface Proteins ◽

Sortase A ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Aureus Infection ◽

Cell Wall Peptidoglycan

The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation...

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A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics

Antibiotics ◽

10.3390/antibiotics8020060 ◽

2019 ◽

Vol 8 (2) ◽

pp. 60 ◽

Cited By ~ 11

Author(s):

Franziska Kampshoff ◽

Mark D. P. Willcox ◽

Debarun Dutta

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Agents ◽

Inhibitory Concentration ◽

Synergistic Activity ◽

Fractional Inhibitory Concentration ◽

First Line ◽

Checkerboard Assay ◽

Resistant Strains ◽

And Staphylococcus Aureus ◽

Broth Dilution

Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa.

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