3D model of Chlamydia’s iron-sensitive gene regulator. Image credit: Pokorzynski et al. (CC BY 4.0)
All forms of life must take up nutrients from their environment to survive. Chlamydia trachomatis, a bacterium that causes many sexually-transmitted infections, is no exception. These bacteria do not normally make one of the building blocks of proteins, the amino acid tryptophan, but instead scavenge it from their human host.
One way that the immune system tries to fight a chlamydia infection is by cutting off the supply of tryptophan in an attempt to starve the bacteria. But the microbes have evolved to respond to these hardships and keep themselves alive. The ‘tryptophan salvage pathway’ is a set of genes that, when switched on, allows the Chlamydia bacteria to take up a molecule found in the female genital tract that they can use to make their own tryptophan. Yet, how do the bacteria know when to activate these genes?
Tryptophan starvation is not the only strategy that the immune system uses to fight chlamydia. It also restricts the supply of the essential metal iron to these bacteria. Now, using human cells grown in the laboratory and infected with Chlamydia bacteria, Pokorzynski et al. show that iron starvation switches on the tryptophan salvage pathway. Chlamydia most likely senses changes in iron levels via a protein called YtgR, and a closer look at the bacterial DNA revealed that YtgR interacts with the genes of the tryptophan salvage pathway. When iron levels were high, YtgR locked on to the DNA in the middle of this set of genes. This effectively switched off the genes on either side of the binding site. When iron levels dropped, YtgR came away from the DNA, releasing the genes and allowing the cell to use them to start making its own tryptophan. Together these findings indicate that, when the bacteria sense that iron levels have dropped, they prepare for a shortage of tryptophan too.
Chlamydia is the most common bacterial sexually transmitted infection worldwide. Left untreated, it can cause infertility and blindness. This and future studies aimed at understanding how these bacteria respond to immune attack may reveal new ways to prevent or treat these infections.
