Pathogenic Microorganisms And Phenotypic Noise: Combat Zone Reconnaissance

“Noisy” Salmonellae in the mouse intestine: the bacteria are green, the cell nuclei of the mouse cells blue and the actin brush-border of the small intestine is red. (Image copyrights: B.Stecher/W.-D. Hardt/ETH Zürich)

ETH Zurich researchers led by Martin Ackermann and Wolf-Dietrich Hardt recently described a remarkable new biological concept: the division of labour via phenotypic noise. This concept is based on the observation that cell divisions of Salmonellae form two specialised groups that perform quite different functions even though they are genetically homogeneous. These groups form when, during cell division, the proteins from the parent cell are distributed randomly rather than uniformly among the daughter clones. This determines how the latter behave.

This phenotypic noise benefits the Salmonellae greatly. One sub-set of the pathogens can penetrate into intestinal cells, where they are recognised and destroyed by the immune system. The other, which lack the properties of the intruders, wait as it were in ambush in the intestinal lumen until the inflammatory host’s immune response induced by the suicidal siblings has punched holes in the intestinal flora, so they can multiply and gain a foothold.

New method finds noisy genes

Whereas in an initial study the researchers focused mainly on a single gene and its products, they have now developed a method with which they can examine the genes of the whole organism. Its purpose is to find genes that are particularly “noisy” and are responsible for the germ’s pathogenicity. The new study was led by doctoral student Nikki Freed.

The new method, which has just been published in the online journal PLoS Genetics, enabled the scientists to filter out two Salmonella genes which regulate the structure of the Salmonella’s flagellae, thus controlling their pathogenicity. The method also allows other prokaryotic or eukaryotic systems to be checked for genes that cause noise.

Targeting coliform bacteria

This is why the researchers want to extend their studies to other bacteria to find out whether phenotypic noise is more widespread than is assumed. They now plan to check Escherichia coli to find out whether this bacterium also employs the division of labour via phenotypic noise. The scientists hope that this will give more clarity as to whether phenotypic noise has established itself as a general principle in biological systems.

Martin Ackermann can also imagine that their discoveries might affect the theory of the origin of multicellular organisms. Expert opinion up to now has been that cells with the same function initially congregated and subsequently combined to develop the multicellular organism’s specialised functions – i.e. its “organs”. Phenotypic noise could turn this theory on its head. It could be that specialised cells could first of all come into being and might then congregate to form a heterogeneous association with various functions, representing the preliminary stage of a multicellular organism. The ETH Zurich professor says, “If we are successful in backing up this hypothesis, we could make a major step in the quest to explain the origin of multicellular organisms.”