Open AccessBacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus
Author(s) -
Haroon Mohammad,
Waleed Younis,
Hany G. Ezzat,
Christine Peters,
Ahmed AbdelKhalek,
Bruce R. Cooper,
Kit Pogliano,
Joe Pogliano,
Abdelrahman S. Mayhoub,
Mohamed N. Seleem
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0182821
Subject(s) - staphylococcus aureus , antibiotics , microbiology and biotechnology , vancomycin , antibiotic resistance , methicillin resistant staphylococcus aureus , antibacterial activity , staphylococcus , bacteria , drug resistance , staphylococcal infections , biology , medicine , genetics
Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents.