Bacteria have an array of strategies for coping with the harsh and
changing environments in the organisms they invade. These include
developing adaptive mutations as they evolve, and activating specific
genes to respond to changes. However, sometimes these defenses aren't
enough, and alternative strategies are needed.
Researchers at the Hebrew University of Jerusalem have discovered a
survival strategy that harmful bacteria can use to outsmart the human
immune response, resulting in more severe and persistent infections and
more effective spreading from person to person.
‘Harmful bacteria develop sub-populations that are each pre-adapted to a different environment or task. This pre-adaptation gives them an extra advantage during invasion and in overcoming the immune system.’
The recently discovered strategy is the generation
of non-genetic variability, in which bacteria develop sub-populations
that are each pre-adapted to a different environment or task. This
pre-adaptation could give invading bacteria an extra advantage during
invasion and in overcoming the immune system. Called phenotypic
variability, this variation involves the development of sub-populations
of bacteria with altered traits such as size or behavior.
To better understand this survival strategy, researchers Irine
Ronin, Naama Katsowitz, Ilan Rosenshine and Nathalie Q. Balaban, led by
Dr. Irine Ronin from the Balaban lab at the Hebrew University of
Jerusalem's Racah Institute of Physics, examined whether non-genetic
variability plays a role in the virulence of a human-specific pathogen,
enteropathogenic E. coli (EPEC), responsible for many infant deaths
Their goal was to uncover whether exposing EPEC to
challenging conditions similar to the ones they would encounter in a
human can trigger EPEC to spontaneously differentiate into different
bacterial sub-populations. To do this, they used mathematical modeling
and genetic analysis.
Their analysis, reported in the peer-reviewed journal eLife
revealed that EPEC spontaneously differentiates into two
sub-populations, one of them particularly virulent, when exposed to
conditions that mimic the host environment. Surprisingly, they found
that once triggered, this hyper-virulent state maintains a very long
memory and remains hyper-virulent for many generations. In addition,
they identified the specific regulatory genes that control the switch
between the non-virulent and hyper-virulent states in EPEC bacteria.
"These results shed new light on bacterial virulence strategies,
revealing the existence of pre-adapted EPEC subpopulations which can
remain primed for infection over weeks," said Prof. Nathalie Q. Balaban.
"They also show that long-term memory drives the expression of the
pathogen's major virulence factors, even upon shifting to conditions
that do not favor their expression."
"The unique memory switch we identified may be common in pathogenic
bacteria, resulting in increased disease severity, higher infection
persistency and improved host-to-host spreading," said Prof. Ilan
Rosenshine. "Further research to characterize the switching mechanism
may point to strategies for tuning down EPEC virulence and fighting
infections, and our approach can provide a framework to search for
similar switches in other pathogens."