The wind storms and heavy rains that hit Seattle a few years ago, and flooded the Battery Street tunnel, demonstrated why a bypass mechanism can be a helpful thing - for both bacteria and motorists.
When the weather is nice, I bike to work. But when the weather gets bad, (I consider rain and 69 mph winds to be BAD), I take the easy way out. On the day of the big windstorm, driving home was not so easy. A mudslide covered one of my usual paths, blocked two lanes on a very busy street, and stopped traffic well into the depths of the city. Since we had to get to a soccer tournament game on time, we had only one choice. Find another route! Luckily, an adventure through the unfamiliar territory of Queen Anne Hill led us to our bypass and got the soccer coach to the game with minutes to spare (in case you're wondering, kids' soccer games in Seattle are rarely cancelled on account of rain or windstorms). Bacteria can use alternate pathways, too. In this case, though, the bacteria don't travel along the pathways. These biochemical pathways are traveled by molecules as they encounter different enzymes and undergo chemical modifications. Unfortunately for us, many antibiotics work by blocking bacterial pathways and killing bacteria. If bacteria find a way to bypass a pathway, they will not be killed by the antibiotic.
Click the image to see a larger picture. The pathway shown on the right outlines two biochemical paths that can be used by the gut bacteria, Enterococcus faecium for synthesizing the rigid subtances in bacterial wells (peptidoglycan). On top, is the pathway that's inhibited by pencillin.
When penicillin (shown in blue), or related antibiotics, bind to the enzymes involved in building the cell wall, the binding is irreversible and the enzyme is inactivated. All traffic stops in that biochemical pathway. The irreversible bond between penicillin and PB4 is colored white. Unfortunately, it looks like some bacteria (at least Enterococcus faecium) are able to use a bypass route and escape pencillin's effects. At least, hopefully, even with the bypass mechanism, penicillin probably still slows down bacterial growth. This is a concern because penicillin and other beta-lactam antibiotics are an important tool for treating severe infections, even after 60 years of use.
1. Cremniter J, Mainardi JL, Josseaume N, Quincampoix JC, Dubost L, Hugonnet JE, Marie A, Gutmann L, Rice LB, Arthur M. "Novel mechanism of resistance to glycopeptide antibiotics in Enterococcus faecium." J. Biol. Chem. 2006 Oct 27;281(43):32254-62.
2. Mainardi JL, Legrand R, Arthur M, Schoot B, van Heijenoort J, Gutmann L. " Novel mechanism of beta-lactam resistance due to bypass of DD-transpeptidation in Enterococcus faecium." J. Biol. Chem. 2000 Jun 2;275(22):16490-6.
3. Mainardi JL, Fourgeaud M, Hugonnet JE, Dubost L, Brouard JP, Ouazzani J, Rice LB, Gutmann L, Arthur M. "A novel peptidoglycan cross-linking enzyme for a beta-lactam-resistant transpeptidation pathway." J Biol Chem. 2005 Nov 18;280(46):38146-52.
Other articles in this series:
1. A primer on antibiotic resistance: an introduction to the question of antibiotic resistance.
2. Natural vs. synthetic drugs: what is the difference between an antibiotics and synthetic drugs?
3. How do antibiotics kill bacteria? a general discussion of the pathways where antibiotics can act and one characteristic that helps some bacteria survive.
4. Are antibiotics really only made by bacteria and fungi? It depends on what you'd like to call them.
5. The Five paths to antibiotic resistance: a quick summary