A quorum is an important thing in many situations. The Keneseth Eliyahoo Synagogue in Mumbai has a problem. Jewish synagogues require what is called the minyan , which means a quorum of 10 people in order to start the prayer. With hardly 4000 Jews left in the city, prayers often get postponed for want of a minyan. On the other hand, business meetings at various offices, which too need a quorum in order to conduct meetings, have found a short-cut rule; when the requisite number is wanting, the meeting is adjourned and reconvened a minute later with the members present.
The need for a quorum goes all the way back in the biological history of bacteria, algae and such unicellular organisms. Here it is not a reconvening of business, but a matter of life and death. Germs infect their victims and feed off them for growth and multiplication. But a single bacterium has no chance. The ‘host’ organism can simply gobble up the invading cell through the grand process called phagocytosis- meaning ingesting the unwelcome ‘guest’ and destroying it.
It is here that bacteria have adopted the idea of a quorum and the principle of ‘unity is strength’. The bacterial cell sends out a chemical signal to recruit more partners for the cause and soon enough they form a sheet or a film- a community of cells-that attaches itself to the surface of the target and live off it. Over 65 per cent of all human infections on the skin, lungs, bladder and other soft tissues occur through such biofilms formed by the invading microbes. Biofilms are also found on medical tools such as catheters, and even on contact lenses worn on the eye. Busting of biofilms is a major problem being studied by biologists the world over.
Clues for discovering or inventing molecules and methods to destroy microbial biofilms come from nature itself. Our own skin and surface tissues release a variety of peptides such as defensins and cathelicidins to fight the invaders. But the sheer variety of microbes, each with its own special features, and each becoming fast resistant to these peptides, has made the matter challenging. What one would like is that magic formula which is universal, broad-spectrum, hitting out against any type of pathogen and dissolving away the films that they make. As on today we do not have such a universal biofilm buster.
It is here that the report by the group of Dr Robert Hancock of the University of British Columbia at Vancouver, Canada offers some hope. Their approach has been to look at a common or universal pathway that all microbes use when they recruit partners to make the adhesive film. The group argued that since the invading microbes themselves are under stress (recall they are starved and need nutrition from the host), it is worthwhile looking at the mechanisms in the bacterial cell which allow it to cope with and responding to such stringent conditions; and that this stringent response system is known to be common to all bacteria and is genetically programmed in them. After all, evolution is economical; once a pathway is found useful, it becomes a genetic hand-me-down.
Two such molecules, common to all microbes, which send out an alarm signal, are referred to as (p)ppGpp. These messenger molecules are highly conserved and seen to be induced by a variety of stress conditions such as starvation, heat and other environmental factors. And they are seen in pathogens such as Pseudomonas, Eschericia coli, Klebsiella, Staphylococcus, Salmonella and others.
These alarm signal molecules, call them alarmones, regulate the expression of a whole host of genes contained in the genomes of the microbe.
Subsequently, the microbial cell sends out signals to recruit partners for the cause, such that they eventually achieve a quorum and the biofilm results.
The Hancock group argued: “what if we find a molecule that can promote degradation and eliminate these alarmones? Such targeting would be a new approach against biofilm-related infections. And resistance to this fundamental and universal cellular step would be far more difficult. And if this molecule does not affect free-floating bugs which do not form biofilms, even better”.
Having tried a few such candidate molecules, the team arrived at an effective and versatile one, which they have named as peptide 1018. This busts the biofilms of a great number of pathogenic bacteria, and thus appears to fit the bill for the much sought after drug.
Their report is published in a recent issue of the journal PLoS Pathogens They have filed a patent application on the use of this biofilm-buster molecule and intend to develop it therapeutically.
dbala@lvpei.org
