Tuberculosis bacteria age–but a Tortoise doesn’t
Microbes are immortal–we used to think. Just two, four, eight forever, while many-celled organisms age and die. The latter may be true of mammals. Reptiles and invertebrates, not so much. A Galápagos tortoise can grow indefinitely, as can a lobster, and a tern might live as long as Elrond. Why them? Go figure.
But a yeast cell ages. A cell of baker’s yeast reproduces by budding off daughter cells, perhaps twenty, while the “mother cell” shrinks and dies. The whole process is controlled by genes and proteins–incredibly, many are “homologs” (share an ancestral gene) with those of human genes that control human aging. No surprise, the study of yeast aging is Big Business.
But bacteria divide in half–two, four, eight. They perpetuate, always the same. Right?
Not so fast. Let’s think about this. A single E. coli cell, or a cell of Mycobacterium tuberculosis, is shaped like a rod, with two poles. The poles remain when the cell divides–the far-left and far-right ends in this micrograph.
But now, what happens in the middle? Two new poles form; you can see where they’re still stuck together. These two new poles are “young.” They haven’t experienced the past few minutes or hours of life during which the far-left and far-right poles aged–perhaps got chewed up by enzymes or toxins in the environment, whatever (we’re not really sure how).
Now imagine the next generation, from two cells to four. We still have two superannuated poles (far-far left, and far-far right), two pairs of middle-aged poles, and two newborn poles in the middle. So these four cells that look identical–have identical DNA–are far from the same. They differ in age. And each half-cell is half as old as its other half. It’s as if half of you were replaced by half of your father or mother.
Is this getting too weird? Why should we care?
We care because half-cell aging explains variable antibiotic resistance in tuberculosis. Which is a big deal, considering totally resistant TB has surfaced in India, and near-total XDR TB occurs in the US and Europe.
Tuberculosis cells are especially weird because one pole grows, while the other doesn’t. The asymmetry and aging of mycobacterial cells (Mycobacterium tuberculosis) leads to vastly different degrees of resistance to different antibiotics. For example, “younger” (faster-dividing) cells are more susceptible to antibiotics that block cell wall growth; whereas “older” (slower-dividing) cells are more susceptible to antibiotics that block RNA. The bottom line: Age diversity leads to antibiotic-resistance diversity, a very bad thing for treatment programs.
If you were a scientist studying all this, what question would you ask next?
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Ultraphyte 
If you were a scientist studying all this, what question would you ask next?
What is difference in the cell walls that makes older cells walls A/B resistant? Is it a change in structure, or is it due to some unrelated biology that impacts the AB.
That’s a great question. One hypothesis would be that, since one pole of the cell doesn’t grow, or grows very slowly, it is insensitive to agents that stop the adding of new cell wall. The way penicillin works, the cell wall stops growing, and falls apart. But we know that cells growing poorly are less sensitive to penicillin. So if a tubercular “half cell” is half protected from an antibiotic, that would be a devious way of resistance all right. It would be interesting to test and see what the cell wall is doing.
I’d probably ask what viruses infect Mycobacterium tuberculosis, since researchers seem more interested in working on viral genetics than on next generation antibiotics.
That’s interesting, there are some viruses (bacteriophages) infecting M. tuberculosis, despite the fact that M. t. has one of the thickest, most impenetrable cell envelopes of any bacterium. Some researchers have even looked at phage therapy.
As a non-scientist, I wonder …
Whether these bacteria are at the older end of the spectrum, i.e., whether less evolved organisms first tried fixing themselves using a band-aid approach before they mastered a complete replication. This in turn suggests differences in whatever mechanisms are associated with more vs. less evolved related species.
What the genomic difference between micro-organisms in terms of pole growth/maturation – number and location of repeats, etc. might be.
Whether whatever makes up and regulates centromeres differs – because I think that’s the bit that actually kick-starts mitosis.
Whether there’s some subtle difference in mRNA which allows the organism to make only a partial copy, so that only part of the original organism gets replaced as it divides.
Also sounds a bit like hemoglobin with its pairs of 2 distinct chains that sometimes don’t reproduce properly (thalassemia, sickle cell disease).