Novel Pentafluorosulfanyl-containing Triclocarban Analogs selectively kill Gram-positive bacteria

The antibacterial and antibiofilm efficacy of our novel pentafluorosulfanyl-containing triclocarban analogs was explored against seven different Gram-positive and Gram-negative indicator strains. After initial screening, they had bactericidal and bacteriostatic activity against Gram-positive bacteri...

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Bibliographic Details
Published in:bioRxiv 2024-01
Main Authors: Pormohammad, Ali, Moradi, Melika, Hommes, Josefien W, Pujol, Eugènia, Naesens, Lieve Mj, Vázquez, Santiago, Surewaard, Bas Gj, Zarei, Mohammad, Vazquez-Carrera, Manuel, Turner, Raymond J
Format: Article
Language:English
Subjects:
Antibacterial activity
Antibiotic resistance
Antibiotics
Bacteriostats
Cell culture
Cell membranes
Ciprofloxacin
Drug resistance
Gentamicin
Gram-positive bacteria
Hydrogen peroxide
Methicillin
Minimum inhibitory concentration
Staphylococcus aureus
Staphylococcus infections
Tissue culture
Toxicity
Triclocarban
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Summary:The antibacterial and antibiofilm efficacy of our novel pentafluorosulfanyl-containing triclocarban analogs was explored against seven different Gram-positive and Gram-negative indicator strains. After initial screening, they had bactericidal and bacteriostatic activity against Gram-positive bacteria, especially Staphylococcus aureus and MRSA (methicillin–resistant staphylococcus aureus) in a very low concentration. Our results were compared with the most common antibiotic being used (Ciprofloxacin and Gentamycin); the novel components had significantly better antibacterial and antibiofilm activity in lower concentrations in comparison to the antibiotics. For instance, EBP-59 minimum inhibitory concentration was < 0.0003 mM, while ciprofloxacin 0.08 mM. Further antibacterial activity of novel components was surveyed against 10 clinical antibiotic resistance MRSA isolates. Again, novel components had significantly better antibacterial and antibiofilm activity in comparison with antibiotics. Mechanistic studies have revealed that none of these novel compounds exhibit any effect on the reduced thiol, disrupting iron sulfur clusters, or hydrogen peroxide pathways. Instead, their impact is attributed to the disruption of the Gram-positive bacterial cell membrane. Toxicity and safety testing on tissue cell culture showed promising results for the safety of components to the host.
DOI:10.1101/2024.01.04.574235