How bacteria die - SGM series

This is the second post of my SGM conference series and the topic is Microbial Death. I was very interested in this one as a topic, because the mechanisms that lead to bacterial death aren't something I've covered so much. It's generally assumed that antibiotics screw up whatever they target such that the bacteria can no longer survive, and when they aren't around the bacteria just keep dividing.

There were two talks concerning antibiotics in bacterial death, the first addressing a theory that's been bandied about for a while (and which I've already written about) that antibiotics don't really kill the cell by acting on their target. Instead, they just lead to sufficient damage to set off a series of death events within the bacteria themselves, a common pathway for bacterial cell destruction (first reference).

I think if I could have chosen any one talk to watch it would have been that talk, actually given by Kohanski whose been working on the stuff. I think there would have been some interesting questions as well, as this is somewhat controversial research.

The other antibiotics talk covered something I'd never heard about; the ability of some antibiotics in certain cases to prevent bacterial death. Work done on Microbacterium turberculosis - which causes TB and a related strain (Microbacterium bovis) showed that when in stationary phase (i.e the bacteria were not growing and dividing) the addition of antibiotics that usually kill only growing cells helped to aid cell survival. Antibiotics that targeted both growing and non growing cells did not have this effect. The reason for this is not clear, however comparing transcriptomes between cells both with and without antibiotics showed a difference in protein production on addition of antibiotics. These antibiotics are in someway helping to turn on genes for survival, which are keeping the stationary phase bacteria alive.

Another interesting talk was about the regulation of mutagenesis in bacteria, another idea I love. It's based on the observation that as bacteria start to get stressed they go into a sort of massive meltdown, leading to lots of genetic mutations being generated. It's been suggested that rather than this being a side-effect of the surrounding stress, this is actually a deliberate ploy by the bacteria to give themselves a last ditch attempt at getting out of a stressful situation.

Unlike multicellular organisms, bacteria have no surrounding restraints on their mutation rate - with the exception of bacteria in aggregates the only thing a bacteria will harm by changing it's DNA is itself. This gives bacteria a lot more genetic plasticity. Added to this, changing DNA is one of the main ways bacteria go about improving themselves, and adapting to new conditions. Changing the DNA by wholescale random mutagenesis is a bit extreme, but if you're in a stressful situation anyway it might be worth a shot.

Studies for this have mostly been done on E. coli, usually a lab strain, so I'm not sure how much they translate into bacteria in the wild, which might be better adapted at coping with stress situations, or, given that experimental bacteria are in a privileged nutritional environment, it might just be too risky for wild bacteria to start messing around with their genome. Also there's no concrete mechanism been found for it yet, so increased mutagenesis producing different phenotypes in times of stress may just be a happy byproduct of the usual genetic craziness that goes on when a cell dies.

These two theories both don't have as much supporting science as they could do, but they are new ideas which are still being worked on, and I really like them both.

---
Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, & Collins JJ (2007). A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 130 (5), 797-810 PMID: 17803904

Ivana Bjedov, Olivier Tenaillon, Bénédicte Gérard, Valeria Souza, Erick Denamur, Miroslav Radman, François Taddei, Ivan Matic (2003). Stress-Induced Mutagenesis in Bacteria Science, 1404-1409 DOI: 10.1126/science.1082240

---
Follow me on Twitter!