Alternate to Antibiotics

I talked in a previous post about research that was being done to determine how to best administer antibiotics in order to mitigate antibiotic resistance. But what about bacteria that are just too virulent to be combatted with typical antibiotics? Kenneth Keiler, professor of biochemistry and molecular biology is working on using something new to stop these virulent strains of bacteria from spreading. In particular, they are currently working with Franscisella tularensis, a pathogenic species of bacteria that can be fatal. It is particularly dangerous as it doesn't take much of the bacteria to infect someone and it can be spread through the air. 

Franscissella tularensis infecting a Macrophage (A type of white blood cell)
Image Courtesy of NIAID

Keiler's group is using two different inhibitors (KKL-10 and KKL-40) to try to stop the bacteria in its tracks. These inhibitors prevent the release of ribosome rescue factors to ribosomes that are stuck translating the same mRNA strand. To help understand what this actually means, we'll go over some basics. Ribosomes are our little protein factories in our cells. They can be found free-floating in our cytoplasm (that gooey stuff that our cell is filled with), or attached to the endoplasmic reticulum. We send a message (mRNA) from our nucleus (where our genetic material is stored) to our ribosomes which then 'translate' that message in to a protein using amino acids as building blocks. The bacteria need constant supplies of proteins in order to stay alive. They need even more to reproduce and infect the body.

Protein Synthesis (big red blob is the ribosome)
Image Courtesy of Biology Discussion Forums

Sometimes ribosomes can get 'stuck' on the same piece of mRNA, and require the release of certain compounds to get 'unstuck'. These compounds, called ribosome rescue factors (which include things like tmRNA, ArfA and ArfB) are able to be blocked by the inhibitors that Keiler's group is utilizing. Stuck ribosomes mean no proteins which means the bacteria eventually will die without reproducing. No bacteria, no infection. Yay you've done it, he's cured!

Being able to cure these difficult infections is becoming ever more crucial, both because of increasing antibiotic resistance and because of the risk of bioterrorism. This risk might been sci-fi, but it is absolutely reality. In fact, the very bacteria that is being tested on in this study was stockpiled during the Cold War to use as a weapon.

When bacteria get too resistant to our current antibiotics, we're shoved right back to ancient medicine (okay, not bloodletting, but still). All we can do it sit and watch and hope the patient's immune system is strong enough to fight it. New, novel methods to cure infections are needed more now than ever.

Keiler's study is going well, and is going into the stages of delivery designs and animal testing.

If you'd like to find out more about his work, you can find his group website here.