Superbugs Antibiotics Antibacterial Strategies Antibacterial Technologies

Our traditional antibiotics are becoming less effective at fighting bacterial infections because they are evolving and becoming resistant.

Bacteria multiply at very high rates which means that any mutations that occur, can be replicated in a very short space of time.  If one mutation means that a strain of bacteria becomes resistant to a particular antibiotic, in very little time, that strain will be the one which survives most.  In short, it becomes the dominant strain.

Mutations occur naturally all the time and it is because some of them improve the survival chances of the species, that evolution gives rise to new species and variations within them.  The same happens to bacteria so gradually evolution improves the survival of the species.  That’s bad news for us because we often want to eradicate bacteria.

Our tools until now have included using broad spectrum antibiotics such as amoxicillin, streptomycin, and others which have usually been effective in defeating many bacterial infections.

But as they evolve better resistance, those antibiotics become less effective.  The recent news that there are news strains of bacteria appearing in the UK, means that there are now categories of bacteria for which we no longer have effective antibiotics.

These new strains contain an enzyme called NDM-1 which makes the bacteria particularly resistant to a powerful group of antibiotics called carbapenems.  These antibiotics are usually reserved for fighting very resistant infections and if there are now bacteria containing enzymes which resist that treatment, the infections cannot be fought.

Genes for the enzyme
If other bacteria acquire the gene to produce NDM-1, then potentially other strains of bacteria could become equally resistant.  But genes evolve naturally because of the constant mutations that occur, and because of the very short life-cycle of bacteria, the rate of evolution is rapid.

So even though this particular strain has come from the Asian sub-continent, it is likely that other bacteria are also evolving similar defence mechanisms against antibiotics.  That means that the whole approach to treating bacterial infections using antibiotics will become progressively less effective.

It is for all the world as though we are stimulating the bacteria to develop defences against the chemicals we use to treat infections.  And it’s a natural process of evolution.

How serious should we treat this?
Of course, if a major weapon for fighting bacterial infections is impaired, many more patients will suffer serious infections.  We can kill bacteria very easily outside of the body using simple methods such as soapy water so cleanliness will prevent the transmission of many infections.

But inside the body, the immune defences are all we have.  Unless we can find better methods for treating these infections, they will become more serious for the patients.

Recourse to non-scientific approaches will not provide effective treatments so alternative therapies offering boosts to the immune system will confuse patients rather than help them.  There are real biological causes and the immune system does not respond to the many alternative therapies claiming to be able to boost it.

There are many infections which have become more resistant to treatment in recent years including tuberculosis, gonorrhoea, malaria and childhood ear infections, and we need new approaches to treatment if we are to overcome the evolved resistance seen in bacteria.

There has been no improved approaches to drug treatment of infection since the introduction of nalidixic acid in 1962 and finding new approaches is increasingly urgent.

Nanotechnology approach
One such approach is the use of synthetic biomolecules called cyclic peptide nanotubes.  These are very small structures which will stack up on the bacterial cell wall effectively punching holes in them killing the cells.  

The synthetic chemicals, cyclic D,L-a-peptides, attack the bacterial cell membrane disrupting the cell’s biochemistry.  They can be synthesised with the properties of attacking specific bacterial cell walls without affecting mammalian cells.

There have been some promising results from the work of Dr M. Reza Ghadiri of the Scripps Research Institute and they have already shown effective treatment of Staphylococcus aureus, a bacterial strain known to be highly antibiotic resistant.  It is estimated that 95% of Staph. aureus strains are resistant to penicillin and 60% to its derivative methicillin.

Bacterial interference
Also known as bacteriotherapy, this technique is to innoculate the patient with a benign strain of the pathogenic bacteria so that the benign form competes for nutrients, preventing the pathogenic form getting a foothold.

The use of competition between strains of bacteria to prevent harmful bacteria taking root is evidenced in the gut where E. coli is naturally constrained in individuals with a normal balanced diet.  The theory is often exploited by food manufacturers making questionable claims about probiotics.

Bacteriophage therapy
This makes use of phages, virus that will attack bacteria.  They are known natural killers of various strains of bacteria and work by taking over the protein manufacture within the bacterial cell, converting it into making viral proteins.

If those viral proteins are engineered to be harmless to the patient, this provides a powerful mechanism for treating bacterial infection.  The technique had been in use in the 1920s to treat cholera, typhoid and dynsentry until synthetic antibiotics took precedence.  It now seems that this approach has increasing value.

Bacterial vaccines
If the specific mechanism for bacterial virulence can be identified by analysing the DNA, then it is possible that an artificial stimulant can be made to produce the effective immune response.  Such vaccinations could then provide very specific immunity to particularly harmful bacterial strains and even lead to their eradication.

Cationic peptides
These form a class of biological molecules found throughout nature in plants and animals which show pronounced antibacterial properties.  They interact with bacterial cell walls destroying the bacterium.  This is a promising area of research but still to produce clear results.

Although the latest news of bacterial resistance is worrying, we should not get it out of proportion.  There are already technologies which we know will be effective and which are being developed.  There are novel approaches which circumvent bacterial antibiotic resistance, and which have a promise of much greater generic effectiveness.

As with all of these medical stories, we should take stock of the bigger picture.  Antibacterial treatments are part of a range of medical technologies being developed based on the growing knowledge base provided by genetics and cellular biology.  Although we shouldn’t simply assume that science will find the answer, we can see measurable progress.