Dual warhead kills and disarms bacteria


A compound that kills bacteria and cleaves their DNA to prevent them passing on drug-resistant genes has been designed by researchers in India.

The increasing ineffectiveness of antibiotics and the absence of suitable new ones are problems long recognised by the medical community. Bacteria can mutate and adapt to become resistant so the stock of effective antibiotics is diminishing. In a recent report, the UK’s Chief Medical Officer stated that increasingly resistant microbes represent a global threat that in the next 20 years could see many more deaths associated with what were routine and safe surgeries.

The bacterial membrane has been identified as bacteria’s achilles heel, given its profound role in the survival of bacteria. Antimicrobial peptides (AMPs) have been used as membrane acting drugs, but they are characterised as being expensive to produce, easily degradable and hard to deliver. The AMP-mimicking synthetic amphiphile developed by Aiyagari Ramesh and his team at the Indian Institute of Technology Guwahati should avoid these problems.

Their synthetic analogue has a cationic pyridinium head group to initiate electrostatic interactions with both the anionic bacterial cell surface and DNA, a 12-carbon chain hydrophobic tail to promote membrane insertion and a planar fluorogenic pyrene group for intercalation with DNA, that also allows Ramesh's team to track these interactions spectroscopically. So the compound attacks bacteria in two ways: it kills bacteria by penetrating their membrane and it disables their resistance mechanism by cleaving the DNA that harbours and disseminates drug-resistance traits. In principle it will be possible to design amphiphiles that selectively target and kill bacteria but leave the surrounding tissue unharmed, and ultimately stop them from becoming superbugs.

Julian Hurdle, whose research at the University of Texas at Arlington, US, evaluates new ways to treat drug-resistant pathogens, is very interested in this approach. ‘The membrane has become a bona fide target site for novel antimicrobial agents that control antibiotic-resistant pathogens.’ He does caution however that ‘to advance this research area it is imperative that we obtain knowledge on the types of chemical groups and physicochemical properties needed to impart significant selectivity for bacterial membranes over their mammalian counterparts.’

References

This paper is free to access until 11 July 2014. Download it here:

D Thiyagarajan et al, Chem. Commun., 2014, DOI: 10.1039/c4cc02354d


Related Content

Pepping up antibiotics

29 September 2014 Premium contentFeature

news image

Industry and academia are turning to antimicrobial peptides to find new antibiotics, Andy Extance discovers

New antibiotic could treat infection while dodging resistance problems

8 January 2015 Research

news image

Technique to tap huge unexplored reservoir of natural products in soil microorganisms finds promising compound

Most Read

Complex amines made easy (and cheap)

22 May 2015 Research

news image

Iron-catalysed cross-coupling brings together nitroarenes and olefins in a single step in boon for drug makers

Opiate-producing yeast raises spectre of 'home-brewed heroin'

18 May 2015 News and Analysis

news image

Warnings that completion of final steps in opiate biosynthesis could be a double-edged sword

Most Commented

The nuclear danger of iodine

20 May 2015 Comments

news image

It may not be an element you think of as problematic. But, as Mark Foreman explains, iodine causes very complicated problems ...

Opiate-producing yeast raises spectre of 'home-brewed heroin'

18 May 2015 News and Analysis

news image

Warnings that completion of final steps in opiate biosynthesis could be a double-edged sword