| Autor: |
Cobongela SZZ; Nanotechnology Innovation Centre (NIC), Health Platform, Advanced Materials Division, Mintek, Randburg 2194, South Africa.; Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg 2050, South Africa., Makatini MM; Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg 2050, South Africa., Mdluli PS; Nanotechnology Innovation Centre (NIC), Health Platform, Advanced Materials Division, Mintek, Randburg 2194, South Africa.; Department of Chemistry, Durban University of Technology, Durban 4000, South Africa., Sibuyi NRS; Nanotechnology Innovation Centre (NIC), Health Platform, Advanced Materials Division, Mintek, Randburg 2194, South Africa.; Department of Science and Innovation (DSI)/Mintek Nanotechnology Innovation Centre (NIC), Biolabels Research Node, Department of Biotechnology, University of the Western Cape, Bellville 7535, South Africa. |
| Abstrakt: |
Acyldepsipeptides (ADEPs) are a new class of emerging antimicrobial peptides (AMPs), which are currently explored for treatment of pathogenic infections, including tuberculosis (TB). These cyclic hydrophobic peptides have a unique bacterial target to the conventional anti-TB drugs, and present a therapeutic window to overcome Mycobacterium Tuberculosis ( M. tb ) drug resistance. ADEPs exerts their antibacterial activity on M. tb strains through activation of the protein homeostatic regulatory protease, the caseinolytic protease (ClpP1P2). ClpP1P2 is normally regulated and activated by the ClpP-ATPases to degrade misfolded and toxic peptides and/or short proteins. ADEPs bind and dysregulate all the homeostatic capabilities of ClpP1P2 while inducing non-selective proteolysis. The uncontrolled proteolysis leads to M. tb cell death within the host. ADEPs analogues that have been tested possess cytotoxicity and poor pharmacokinetic and pharmacodynamic properties. However, these can be improved by drug design techniques. Moreover, the use of nanomaterial in conjunction with ADEPs would yield effective synergistic effect. This new mode of action has potential to combat and eradicate the extensive multi-drug resistance (MDR) problem that is currently faced by the public health pertaining bacterial infections, especially TB. |
