Combat of Multidrug Resistant Pathogens: Discovery of Novel Compounds Against Multidrug Resistant Staphylococcus Species
Farah Ibrahim Al-Marzooq,1 Dr Srinivasulu Vunnam,1 Taleb H. AL-Tel*1,2
1Sharjah Institute for Medical Research and 2College of Pharmacy
University of Sharjah, Sharjah, 27272 UAE
Multidrug resistance is non-susceptibility to at least one agent in three or more antimicrobial categories (Magiorakos et al., 2012). Staphylococcus is one of most clinically important species of Gram-positive bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of severe infections in health care facilities and the community. World health organization has included this bacteria in the list of top 12 pathogens causing high morbidity and mortality worldwide (WHO, 2017). Novel antibacterial agents with unique chemical scaffolds are urgently required to combat the resistant bacteria.
In this study, the group have developed new method for the synthesis of novel compounds which to the best of our knowledge has never been disclosed in the literature. These compounds were produced in one-pot at a large scale from cheap and commercially available starting materials.
Minimum inhibitory concentrations (MICs) of the compounds were determined using broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines (CLSI, 2015). For the definite determination of MICs, CellTiter-Blue® Cell Viability Assay (Promega, USA) was used. The compounds were tested against 10 multidrug-resistant strains of Staphylococcus species including S. aureus (3 MRSA strains), S. saprophyticus (4 strains), S. haemolyticus (2 strains), and S. epidermidis (1 strain). Some compounds were 10-20 times more potent than ciprofloxacin as indicated by difference in MICs of the compounds compared to ciprofloxacin. We have developed novel small molecules that inhibit bacterial growth, including multidrug resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). These molecules can modulate the patient immunity and fight infections effectively. This innovation has immediate relevance for treating and preventing many life-threatening infections.