Field of Science

Resistance without genetics - persistance in bacterial populations

Most work on bacterial resistance to antibiotics tends to start with genetics. If a bacteria is able to survive a certain antibiotic, it is assumed that it has gained a gene from somewhere (and bacteria can get genes from almost anywhere) which allows it to survive. That makes sense after all...surely two bacteria with exactly the same genetic information should react identically to antibiotics?

No. Not all the time. There is an unfortunate habit of biochemists to get too wrapped up in the genetics to think about epigenetics (control of genetic expression by proteins), especially with 'simpler' organisms like bacteria. Persistence is the property of a totally identical population of bacteria to respond differently to antibiotics, despite having identical genomes they are phenotypically (phenotype = set of observable characteristics) different.

Persistent bacteria aren't only seen in response to antibiotic's either...they can be found for many types of stress, such as heat or starvation. They've been roughly split into two different types:
  • Type I persisters: form in response to stress, usually at stationary phase (i.e after the initial burst of bacterial growth)
  • Type II persisters: are seen forming throughout the bacterial lifecycle
Monitoring the growth rates of individual cells showed that even before treatment with antibiotics, many of the persister cells had reduced growth rates. The mechanism for this is not yet clear, a few genes that may be involved have been identified, but no reason for activating them (or repressing them in non-persisters), has yet been identified.

Although these sound dangerous at first glance, the medical implications of persisters are relatively limited (probably the reason why the mechanism has not been more thoroughly studied). As they have a slower growth rate, and as there are so few of them within an overall susceptible population, they can usually be cleared relatively easily by the immune system. There are, therefore, only three main areas where they are clinically relevant: immunosuppressed patients, pathogens that have adapted to the immune system, and in niches in the body that are less available to the immune system (such as within a biofilm).

The main ecological and evolutionary implications of this are that a colony of identical bacteria can 'survive' antibiotic attack by having a few of its members able to withstand that attack. Although they will grow slower under normal conditions, their ability to withstand stressful conditions means that they can essentially recover the whole colony, without the need for a major genetic change. This is true especially of diseases such as tuberculosis, where very few bacteria are needed to re-start an infection.

One thing that would be really interesting would be to study the behaviour of persisters within biofilms. Along with swarming and quorum sensing, biofilms are an example of pseudo-multicellular bacterial behaviour, circumstances under which having a small population of cells that can regenerate the whole colony would be very useful.


Orit Gefen & Nathalie Q. Balaban (2009). The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress FEMS Microbiology Reviews, 33 (4) : 10.1111/j.1574-6976.2008.00156.x


Jim said...

There is an unfortunate habit of biochemists to get too wrapped up in the genetics to think about epigenetics

I would say that on the whole, most biochemists who think of themselves as biochemists would generally not give a jot about the genetics either (I say this as a trained biochemist who has worked in bacterial molecular genetics for the better part of 10 years).

On the whole, bacterial molecular genetics, or molecular microbiology, has become quite multidisciplinary, thus its a little anachronistic to typify any one discipline...except possibly biophysicists, lol

Epigenetics is a very exciting subject area right now; it has long been known, but we're only really getting to the point where we have the kind of high through-put methodologies to actually probe epigenetic changes with any degree of relevance.

However, whilst I think that epigenetic changes certainly do have a role to play, describing such phenotypic (as opposed to geneotypic) variants, another model that can describe the properties we see in persisters is that of cell senescence (you can read an article on it here (You should be able to download the full text freely).

Nice blog by the way, keep it up.

mahrou said...


unfortunately i couldn’t find your email.i am a student from the university of Edinburgh, right now i am working on my dissertation which is on science blogs, i have chosen the island of doubt blogger to interview and i also need to interview some of the other blogs who comment on his posts, i was wondering if you could help me and let me interview as well?

Best Regards,

Lab Rat said...

@Jim: perspective on biochemists comes from being 3/4 of the way through a biochemistry degree...they seem to be fairly heavy handed on finding genes for things, and most of my practical experiance was in pathology labs, where I assumed people thought about things a little differently.

Thanks for the comments!