ANU Open Research Repository has been upgraded. We are still working on a few minor issues, which may result in short outages throughout the day. Please get in touch with repository.admin@anu.edu.au if you experience any issues.
 

Insights into an evolutionary strategy leading to antibiotic resistance

Date

2017-01-11

Authors

Hou, Chun-Feng D
Liu, Jian-Wei
Collyer, Charles
Mitić, Nataša
Pedroso, Marcelo Monteiro
Schenk, Gerhard
Ollis, David L

Journal Title

Journal ISSN

Volume Title

Publisher

Nature Publishing Group

Abstract

Metallo-β-lactamases (MBLs) with activity towards a broad-spectrum of β-lactam antibiotics have become a major threat to public health, not least due to their ability to rapidly adapt their substrate preference. In this study, the capability of the MBL AIM-1 to evade antibiotic pressure by introducing specific mutations was probed by two alternative methods, i.e. site-saturation mutagenesis (SSM) of active site residues and in vitro evolution. Both approaches demonstrated that a single mutation in AIM-1 can greatly enhance a pathogen's resistance towards broad spectrum antibiotics without significantly compromising the catalytic efficiency of the enzyme. Importantly, the evolution experiments demonstrated that relevant amino acids are not necessarily in close proximity to the catalytic centre of the enzyme. This observation is a powerful demonstration that MBLs have a diverse array of possibilities to adapt to new selection pressures, avenues that cannot easily be predicted from a crystal structure alone.

Description

Keywords

Citation

Source

Scientific reports

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

DOI

10.1038/srep40357

Restricted until