Wednesday, 9 July 2014

On Microbial Antagonism, Antibiotics and Antibiotic Resistance

I am giving a course on Great Scottish Scientists at Strathclyde University and just started my talk on Alexander Fleming - who discovered penicillin in 1928.

The history of infectious diseases is fascinating.  Look closely at how life operates in nature and one can't help but marvel at the complex way different lifeforms interact. The delicate balance among species in nature must not be disturbed; something mankind is doing without regard to consequences. Come to think of it - we humans do a lot of things which can only be called irresponsible - but that is another story.

All life forms in nature operate on the same principle; it is the fight for survival.  Two essentials for survival are nutrients and space and this is what they all compete for.  From humans to microbes - it is the same struggle. Compete to survive!  Sometimes clever associations are formed for mutual benefits - ecosystems operate that way.  You break the chain by removing one species and part of the system collapses.

Historically, humans have suffered various forms of diseases caused by bacteria and viruses (microbes).  At times 50% of the population in Europe died because of rampant infections.  Louis Pasteur confirmed that such infectious diseases are caused by microbes whose sole aim appears to wish to increase their numbers and if humans could help them, then so be it.  Edward Jenner successfully developed vaccinations against smallpox and vaccination has proved to be very effective in controlling some diseases. Joseph Lister made surgery so much safer by using antispetics like phenol and alcohol.

But that is only a limited success.  Harmful bacteria lurk everywhere - from rose bushes to rusted nails.  Even human bodies harbour harmful bacteria which attack when the system is in a weakened state.

Let us not get it wrong - bacteria and viruses do not only attack and harm humans or big life forms.  They are fighting with each other with equal intensity.  Bacteria grow rapidly and need the resources - other microbes which come in their way have to watch out.  The best way to deal with the situation is by chemical means - produce chemicals that are toxic to invading bacteria.  This has been happening throughout the nature.  Plants produce such chemicals to fight microbial attacks, fungii do it, bacteria do it and we humans do it as well.
In 1922, Alexander Fleming discovered Lysozyme in human mucas, tears; in egg white and in all sort of places.  Lysozyme, as the name suggests, is an enzyme that lyses (dissolves) bacteria; but it only effects a few of them.

But what about using the chemicals that microbes produce to fight other microbes.  If we can find the right chemical that kills the infection-causing bacteria then we can use it to control the infection. Bacterial antagonism can really be put to good use.   Of course, the chemical must be tolerated by the human body and not be toxic so as to harm us as well. Gramicidin discovered in 1936 by Rene Dubos was one such chemical - good to kill bacteria but also toxic to humans - so no use to us.
Alexander Fleming discovered penicillin in 1928.  It is produced by the fungus penicillin notatum and the best source was found to be a cantaloupe in Illinois, USA!  Penicillin was found to be effective against gram positive bacteria (these are bacteria that have a particular type of membrane wall structure) and was effective in killing lot of infection causing microbes - pneumonia, meningitis and a whole lot more.  Penicillin is also tolerated by human body very well and this was to become an ideal weapon for fighting infections.
We call this class of chemicals antibiotics.
Streptomycin is another anitbiotic that was discovered by Selman Waksman in 1943 and it was very effective in fighting tuberculosis.

1940s and 50s were really the golden age of antibiotics.  Many more were discovered or synthesized, mainly derivatives of penicillin.  Penicillin alone saved millions of lives.

The thing about life is that there is never a final chapter.  Bacteria don't like getting killed this way and we soon started to see resistant strain of bacteria showing up.  The resistant strain are not affected by the antibiotic any more and we go back to either finding a new antibiotic that is effective in killing the bacteria or have the problem of reverting back to pre-antibiotic age when infections were a real problem.
Bacteria are great in producing resistant strains.  They have survived billions of years because they can quickly and efficiently adapt to changing environments. They multiply fast - so population of resistant bacteria builds up rather quickly. Bacteria mutate frequently and then they have at their disposal clever schemes for defeating the antibiotic attacks.  Bacteria can produce enzymes that breakdown the antibiotic molecules making them ineffective or they can cover the region where antibiotic would bind to the cell.  They also exchange resistant genes with other bacteria in the vicinity and spread the resistant genes very efficiently.

It is thus an ongoing war.  We have to keep inventing/discovering new antibiotics - stronger and stronger ones to fight the resistant strains. Something, we have not done very well for the past 40 years or so.  Drug companies did not see much money in this pursuit and governments also got complacent.  But now the problem of resistant bacteria is such that people are waking up to the reality - Alexander Fleming warned about this in 1945 and we all could see this coming but not much was done in the interim.

Even more complicated situation has arrived in the form that many bacterial strains are resistant to several antibiotics with some now resistant to all known antibiotics.  We soon will come full circle here.

In the highly developed societies with good hygiene and clean environment, people do not normally suffer many minor infections.  This also means that they do not develop immunities the same way as societies in the past, who were exposed to many more microbes as routine, did. We also live in much more crowded cities and we travel more. All this can spread infections quickly and efficiently.  When an infection strikes, we shall be less well prepared and the death rates will be correspondingly higher.

The prognosis is not good.
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