Bacteria Develop New pH Sensitivity Under Environmental Extremes

Bacteria can acquire an increased sensitivity to acid levels after being subjected to contrasting environmental extremes in the laboratory, new research reveals.

This ability sets off a cascade of altered gene expression, enabling the microbes to reshape themselves around continually fluctuating conditions.

From the tiniest cells to the biggest whales, every form of life must contend with environmental conditions that constantly shift and cycle.

Testing Escherichia coli under environmental extremes

To learn more about how organisms can physiologically adapt to such extremes, microbiologist Sarah Worthan of Vanderbilt University in Nashville and her colleagues drove Escherichia coli bacteria to their limits.

Several bacterial populations swiftly evolved genetic mutations that allowed them to prosper. Cancer cells also exploit the resulting mutations to build a more favourable environment for themselves.

"Our results suggest [these mutations] may serve to rapidly coordinate complex physiological responses through pH sensing and shed light on how cellular populations use environmental cues to coordinate rapid responses to complex, fluctuating environments," the researchers write in their paper.

Worthan and her team produced an intense laboratory equivalent of changing environments by placing 16 populations of E. coli through periods of severe, prolonged starvation, then moving them to a fresh, nutrient-rich setting before repeating the cycle.

While the microbes were starving, metabolic waste built up and dramatically altered the pH of their surroundings. Every 100 days, the bacteria received a new supply of resources and a fresh start, recreating the feast-and-famine cycle that life commonly encounters in nature.

How pH sensing changes bacterial gene expression

A change to a single protein building block emerged and spread through seven bacterial populations, usually during just the experiment's first 300 days. This amino-acid substitution, replacing arginine with histidine, occurred in the Rho protein, a molecule that tells the bacteria's protein-producing machinery when to stop making proteins.

"This mutation in rho repeatedly arose in our laboratory evolution cultures," explains Vanderbilt University microbiologist Megan Behringer.

"We returned to our genomic data and noticed that every mutation in rho co-occurred with a mutation in a gene named 'ydcI.' Not much is known about this gene, but very recent studies suggested that it may have a role in pH homeostasis."

The usual Rho protein helps bacterial cells perform better during abundant conditions, yet becomes a disadvantage when they experience famine. Worthan and the team discovered that mutated ydcI enabled cells to tolerate alterations to the Rho protein more effectively.

The ydcI mutation seems to respond to changing pH. It therefore functions as a switch activated by environmental change, which in turn initiates changes inside individual cells.

"Even though bacteria interact with each other through their extracellular environment, individual cells have some control over their intracellular environments," says Bratton.

Together, these genes make it easier for cells to physiologically adapt to continuously changing environmental conditions. The researchers identified several instances of this same mechanism in nature.

Similar pH sensing in pathogens and cancer

"We found it in this neglected pathogen, Bartonella bacilliformis, which causes Carrion's Disease in the Andean valleys of South America," says Behringer.

"This species of bacteria was already known to pH sense as it must rapidly adjust from the high pH insect gut to the neutral pH of human blood when it's transmitted by its sand fly vector."

Strong adaptation of this kind gives cells an advantage over competitors, as demonstrated by cancer. Cancers seem to use a comparable mechanism to raise their internal pH, producing a cascade of altered gene expression that is then used to reshape the surrounding cellular environment.

These findings demonstrate "the power of experimental evolution for identifying functionally important mutations relevant to natural environments," Worthan and her colleagues conclude.

The research was published in PNAS.