Return to News

The hunger games of genes and microbes

by Angela Herring

When the going gets tough in the micro­scopic world of bac­teria, one of the best bets is to form a biofilm, an immo­bile colony of cells that offers pro­tec­tion against harsh con­di­tions. Think of it as a force field that ensures sur­vival on the inside and keeps external invaders at bay.

It’s a good strategy, if you’re a bac­terium. But for people suf­fering from chronic infec­tions such as MRSA and Lyme dis­ease, biofilms are some­times the cul­prits that make healing a nearly impos­sible feat. How­ever, North­eastern Uni­ver­sity assis­tant pro­fessor of biology Yun­rong Chai and his team have dis­cov­ered a new mech­a­nism for biofilm for­ma­tion that could offer valu­able insight into treating these kinds of infections.

Bac­teria are expert envi­ron­ment sen­sors. They con­stantly mon­itor their sur­round­ings for sig­nals that tip them off to trouble. Their so-​​called “mol­e­c­ular machines” skill­fully rec­og­nize envi­ron­mental cues such as for­eign chem­i­cals or reduced oxygen sup­plies. Nearly every sensing mech­a­nism that sci­en­tists are cur­rently aware of depends on one of these ded­i­cated “machines,” Chai said.

How­ever, in work recently reported in the open-​​access journal eLife, Chai and his col­leagues explain that their new mech­a­nism doesn’t have a ded­i­cated sensor working for it. Instead, it takes advan­tage of a nat­u­rally occur­ring “flaw” in gene expres­sion to turn on biofilm for­ma­tion when nutri­tional resources are low.

Here’s how it works: When food becomes scarce and the sugars and starches that bac­teria nor­mally eat begin to dwindle, the bac­teria turn to amino acids instead—these are the building blocks of pro­teins, and each is coded by a few dif­ferent sequences in the DNA.

Mol­e­cules called ribo­somes read these sequences to build pro­teins by selecting and laying down the appro­priate amino acids like a steel driver laying train ties. For example, the amino acid serine gets laid down every time the ribo­some runs across one of six “codons,” which are three-​​lettered sequences that cor­re­spond to sub­units of DNA

But when a ribo­some encoun­ters cer­tain kinds of codons, it gets stopped in its tracks—in the case of serine, four of these six codons can act as the culprit—and this is espe­cially true when the amino acid in ques­tion is in low supply.

Sci­en­tists have long won­dered why such “bad” codes should exist at all. But, Chai thought, “maybe bad isn’t always bad.” Maybe there’s a method behind this genetic madness.

Chai’s team found that such is the case with a gene called SinR, which is known to inhibit biofilm for­ma­tion. Many of the serine codons in this gene sequence are the “bad” kind, but instead of being faulty Chai believes they serve an impor­tant pur­pose. When serine levels are low because the bac­teria are eating it instead of their normal food, the ribo­somes get stopped by those bad codons more often and as a result have a harder time making the pro­teins that block biofilms.

Ergo, low nutri­tional resources lead to biofilm for­ma­tion. It sounds like a pretty good strategy.

One of Chai’s col­leagues dis­cov­ered sim­ilar activity in human cancer cells, sug­gesting that this mech­a­nism could be gen­er­al­iz­able to a lot of dif­ferent species—not just bac­teria. Indeed, it may be some­thing all our cells do to reg­u­late gene expres­sion in response to par­tic­ular envi­ron­mental signals.

Originally published in news@Northeastern on February 6, 2014.

« »