Status of Targeting MreB for the Development of Antibiotics.

Elvis Awuni

doi:10.3389/fchem.2019.00884

Abstract

Although many prospective antibiotic targets are known, bacterial infections and resistance to antibiotics remain a threat to public health partly because the druggable potentials of most of these targets have yet to be fully tapped for the development of a new generation of therapeutics. The prokaryotic actin homolog MreB is one of the important antibiotic targets that are yet to be significantly exploited. MreB is a bacterial cytoskeleton protein that has been widely studied and is associated with the determination of rod shape as well as important subcellular processes including cell division, chromosome segregation, cell wall morphogenesis, and cell polarity. Notwithstanding that MreB is vital and conserved in most rod-shaped bacteria, no approved antibiotics targeting it are presently available. Here, the status of targeting MreB for the development of antibiotics is concisely summarized. Expressly, the known therapeutic targets and inhibitors of MreB are presented, and the way forward in the search for a new generation of potent inhibitors of MreB briefly discussed.

Highlights

The emergence of antibiotic-resistant bacterial strains (White et al, 2011; Ventola, 2015; Frieri et al, 2017; Li and Webster, 2018; Thorpe et al, 2018) has aggravated the challenges posed by bacterial infections to public health (Founou et al, 2017), resulting in the need to find new antibacterial agents
CptA (Figure 2I) is an E. coli toxin that inhibits the polymerization of MreB and FtsZ, and its effect is neutralized by the antitoxin CptB (Masuda et al, 2012b)
Targeting the ATP binding site of MreB for the development of antibiotics has not recorded any major successes partly because the development of ATP-competitive inhibitors is normally not so appealing to researchers as the inhibitors stand a higher chance of being non-specific as a consequence of the conserved nature of ATP binding sites among prokaryotes and eukaryotes (Škedelj et al, 2011)

Summary

Elvis Awuni*

Many prospective antibiotic targets are known, bacterial infections and resistance to antibiotics remain a threat to public health partly because the druggable potentials of most of these targets have yet to be fully tapped for the development of a new generation of therapeutics. The prokaryotic actin homolog MreB is one of the important antibiotic targets that are yet to be significantly exploited. Notwithstanding that MreB is vital and conserved in most rod-shaped bacteria, no approved antibiotics targeting it are presently available. The status of targeting MreB for the development of antibiotics is concisely summarized. The known therapeutic targets and inhibitors of MreB are presented, and the way forward in the search for a new generation of potent inhibitors of MreB briefly discussed

INTRODUCTION

FUNCTION OF MreB

DISCOVERY AND DEVELOPMENT

INHIBITORS OF MreB

Other Inhibitors

DISCUSSION AND FUTURE