Eslam Ibrahim         email
Institute for Molecular Infection Biology

 

Supervisor:
PD Dr. Knut Ohlsen (Würzburg)
Promotion Committee: 
PD Dr. Knut Ohlsen (Würzburg)
PD Dr. Wilma Ziebuhr (Würzburg)
Dr. Martin Fraunholz (Würzburg) 

 

 

Regulation of antibiotic resistance in Staphylococcus aureus by small RNAs

Infections due to antibiotic resistant staphylococci are still a major threat for patients in hospitals. Recently, the synthesis of a novel class of naphthalimides and its anti-infective activity against Staphylococcus aureus and other gram-positive pathogens have been reported. The most active compound called MT02 directly interacts with the DNA of staphylococci.

Further studies revealed that S. aureus is able to develop a resistance against MT02 when selected in increasing concentrations of the compound. The resistance development includes an inactivation of the drug by the reduction of the two critical nitro-groups to two amino-groups.

In an attempt to answer the question of whether staphylococcal nitroreductases could be involved in this reductive resistance mechanism, the role of a novel staphylococcal nitroreductase and its regulation by a small regulatory RNA shall be investigated on a molecular level including expression analysis, characterization of mutant strains lacking the nitroreductase as well as the small RNA, stress-related growth experiments, and in vitro cell culture-based experiments. The studies will give novel insights into the regulatory impact of small RNAs on antibiotic resistance development.