An alternative approach to combat microbial infections by peptide induced inhibition of ATP Synthase
Contributors:
Muizz Merchant
Sofiya Azim
Thomas F. Laughlin
Zulfiqar Ahmad
Muizz Merchant
Sofiya Azim
Thomas F. Laughlin
Zulfiqar Ahmad
Participating Organizations:
Department of Biochemistry, Kirksville College of Osteopathic Medicine
MOSDOH, A.T. Still University, Kirksville, MO
Department of Biological Sciences, East Tennessee State University
Department of Biochemistry, Kirksville College of Osteopathic Medicine
MOSDOH, A.T. Still University, Kirksville, MO
Department of Biological Sciences, East Tennessee State University
Background
A variety of anti-microbial and anti-tumor peptides are known to bind and inhibit ATP synthase. Peptide-induced inhibition of Escherichia coli ATP synthase establishes that the anti-microbial and anti-tumor effects of peptides are in part linked to the blocking of ATP synthesis in tumor and bacterial cells. Our lab has studied the inhibitory effects of a variety of α-helical cationic peptides on E. coli ATP synthase.
A variety of anti-microbial and anti-tumor peptides are known to bind and inhibit ATP synthase. Peptide-induced inhibition of Escherichia coli ATP synthase establishes that the anti-microbial and anti-tumor effects of peptides are in part linked to the blocking of ATP synthesis in tumor and bacterial cells. Our lab has studied the inhibitory effects of a variety of α-helical cationic peptides on E. coli ATP synthase.
Methods
Wild-type E. coli strain, pBWU13.4 growth properties were checked on fermentable glucose and non-fermentable succinate carbon sources before harvesting cells in minimal media to isolate ATP synthase. Peptide-induced inhibitory studies were performed on membrane bound F1Fo ATP synthase. An additional positive charge in the form of a c-terminal NH2 group was added to augment the extent of inhibition.
Wild-type E. coli strain, pBWU13.4 growth properties were checked on fermentable glucose and non-fermentable succinate carbon sources before harvesting cells in minimal media to isolate ATP synthase. Peptide-induced inhibitory studies were performed on membrane bound F1Fo ATP synthase. An additional positive charge in the form of a c-terminal NH2 group was added to augment the extent of inhibition.
Results
A large variation on the extent and potency of inhibition was observed for natural and modified peptides. We found that addition of a c-terminal NH2 group on natural peptides makes them potent inhibitors on a molar scale. These studies also demonstrated that peptides follow a differential pattern of inhibition of ATP synthase. Our results have also confirmed that incremental addition of positively charged residues can enhance the inhibitory effects of peptides by about 100-fold. Thus, making ATP synthase a potent molecular drug target for anti-microbial and anti-tumor peptides. Currently, we are studying the synergetic inhibitory effects of peptides on ATP synthase.
A large variation on the extent and potency of inhibition was observed for natural and modified peptides. We found that addition of a c-terminal NH2 group on natural peptides makes them potent inhibitors on a molar scale. These studies also demonstrated that peptides follow a differential pattern of inhibition of ATP synthase. Our results have also confirmed that incremental addition of positively charged residues can enhance the inhibitory effects of peptides by about 100-fold. Thus, making ATP synthase a potent molecular drug target for anti-microbial and anti-tumor peptides. Currently, we are studying the synergetic inhibitory effects of peptides on ATP synthase.
Conclusions
We conclude that α-helical cationic peptides are potent inhibitors of E. coli ATP synthase. Our data also suggests that the inhibitory potency of ATP synthase by AMPs can be enhanced through modification of peptides and the selective inhibition of bacterial ATP synthase is a novel way for the development of antibiotics.
We conclude that α-helical cationic peptides are potent inhibitors of E. coli ATP synthase. Our data also suggests that the inhibitory potency of ATP synthase by AMPs can be enhanced through modification of peptides and the selective inhibition of bacterial ATP synthase is a novel way for the development of antibiotics.
