Article

Tackling antibiotic resistance: a dose of common antisense?

Antibiotic Resistance Monitoring and Reference Laboratory, Centre for Infections, Health Protection Agency, London NW9 5EQ, UK.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.44). 12/2008; 63(2):225-9. DOI: 10.1093/jac/dkn467
Source: PubMed

ABSTRACT Resistance to antimicrobial agents undermines our ability to treat bacterial infections. It attracts intense media and political interest and impacts on personal health and costs to health infrastructures. Bacteria have developed resistance to all licensed antibacterial agents, and their ability to become resistant to unlicensed agents is often demonstrated during the development process. Conventional approaches to antimicrobial development, involving modification of existing agents or production of synthetic derivatives, are unlikely to deliver the range or type of drugs that will be needed to meet all future requirements. Although many companies are seeking novel targets, further radical approaches to both antimicrobial design and the reversal of resistance are now urgently required. In this article, we discuss 'antisense' (or 'antigene') strategies to inhibit resistance mechanisms at the genetic level. These offer an innovative approach to a global problem and could be used to restore the efficacy of clinically proven agents. Moreover, this strategy has the potential to overcome critical resistances, not only in the so-called 'superbugs' (methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci and multidrug-resistant strains of Acinetobacter baumannii, and Pseudomonas aeruginosa), but in resistant strains of any bacterial species.

Download full-text

Full-text

Available from: David Wareham, Jun 19, 2015
0 Followers
 · 
117 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The rise and spread of antibiotic resistance is among the most severe challenges facing modern medicine. Despite this fact, attempts to develop novel classes of antibiotic have been largely unsuccessful. The traditional mechanisms by which antibiotics work are subject to relatively rapid bacterial resistance via mutation, and hence have a limited period of efficacy. One promising strategy to ameliorate this problem is to shift from the use of chemical compounds targeting protein structures and processes to a new era of RNA-based therapeutics. RNA-mediated regulation (riboregulation) has evolved naturally in bacteria and is therefore a highly efficient means by which gene expression can be manipulated. Here, we describe recent advances toward the development of effective anti-bacterial therapies, which operate through various strategies centered on RNA.
    Frontiers in Genetics 11/2013; 4:230. DOI:10.3389/fgene.2013.00230
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Healthcare-acquired infections with methicillin-resistant Staphylococcus aureus (MRSA) are a significant cause of increased mortality, morbidity and additional health care costs in United States. Surface decontamination technologies that utilize pulsed xenon ultraviolet light (PPX-UV) may be effective at reducing microbial burden. The purpose of this study was to compare standard manual room-cleaning to PPX-UV disinfection technology for MRSA and bacterial heterotrophic plate counts (HPC) on high-touch surfaces in patient rooms. Rooms vacated by patients that had a MRSA-positive polymerase chain reaction or culture during the current hospitalization and at least a 2-day stay were studied. 20 rooms were then treated according to one of two protocols: standard manual cleaning or PPX-UV. This study evaluated the reduction of MRSA and HPC taken from five high-touch surfaces in rooms vacated by MRSA-positive patients, as a function of cleaning by standard manual methods vs a PPX-UV area disinfection device. Colony counts in 20 rooms (10 per arm) prior to cleaning varied by cleaning protocol: for HPC, manual (mean = 255, median = 278, q1-q3 132-304) vs PPX-UV (mean = 449, median = 365, q1-q3 332-530), and for MRSA, manual (mean = 127; median = 28.5; q1-q3 8-143) vs PPX-UV (mean = 108; median = 123; q1-q3 14-183). PPX-UV was superior to manual cleaning for MRSA (adjusted incident rate ratio [IRR] = 7; 95% CI <1-41) and for HPC (IRR = 13; 95% CI 4-48). PPX-UV technology appears to be superior to manual cleaning alone for MRSA and HPC. Incorporating 15 minutes of PPX-UV exposure time to current hospital room cleaning practice can improve the overall cleanliness of patient rooms with respect to selected micro-organisms.
    BMC Infectious Diseases 04/2014; 14(1):187. DOI:10.1186/1471-2334-14-187 · 2.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pseudomonas aeruginosa chronically infects patients with cystic fibrosis and is associated with greater morbidity. There has been limited progress on the clinical development of new antibiotics with novel modes of action. This review addresses some of the latest research developments on the exploitation of candidate adjuvant therapeutic agents that may act alongside conventional antibiotics as an alternative therapeutic strategy. After considering key mechanisms this opportunistic pathogen employs to control virulence, the progress of various strategies including the inhibition of quorum sensing, efflux pumps and lectins, and the use of iron chelators, bacteriophages, immunisation and immunotherapy is reviewed. Both therapeutic approaches in early development and clinical phase are discussed.
    European Respiratory Journal 06/2012; 40(4):1014-23. DOI:10.1183/09031936.00042012 · 7.13 Impact Factor