Histones are present in large numbers in most animal
cells. They function to compact 3 meters
of DNA so it can fit inside the nucleus.
That, however, appears to not
be their only job. Strangely enough, there
is some evidence that histones can protect cells against bacteria. How on earth can a DNA-bound protein aid the
immune system to mount an antibacterial response?? And how can a nuclear
protein attack bacteria that, from what I know, multiply in the cytosol not in
the nucleus? Additionally, I thought
free histones could be damaging to cells?
Too many questions! Turns out our
cells may have found a way around these limitations. Namely, histones bound to intracellular
lipids. A group from the University of
California Irvine isolated lipid droplets from Drosophila embryos and showed that it is these lipid-bound histones
that can be released to kill bacteria. They
tested this antibacterial ability of histones by injecting bacteria into wild-type Drosophila
embryos, containing lipid-bound histones, and into lipid-bound histone knockout
embryos. Turns out, the knockouts were 14 times more likely to die of the bacterial
infection. Is this just in flies? No. It
appears some data shows that this antibacterial role of histones may be present
in mice. Researchers have also
identified lipid-bound histones in human cells as well. What does this mean for humans? Could histones be manipulated to aid in the
immune response?
Anand et. al., A novel role for lipid droplets in the organismal antibacterial response. eLife 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491588/pdf/elife00003.pdf
This is potentially interesting considering that the same lipid droplets that these histones are bound to in the cytosol, have been linked as a site for viral replication. Bacteria versus virus... hmmmm
ReplyDeletePlus, since the mechanism of bacterial protection is unclear, and research has been reported that lipid bound histones may act to "prevent excess histones from affecting cellular processes", it may just be that an accumulation of histones inhibits a cell's ability to fight bacterial infections?
Jones, Bryony. Organelle dynamics: A histone anchor on lipid droplets. Nature reviews molecular cell biology. 2012.
Walther TC and Farese RV. Lipid Droplets and Cellular Lipid Metabolism. Annual Review of Biochemistry. 2012.
Antimicrobial peptides ( AMPs) are part of the innate immune system and kill or damage bacterial and fungal pathogens. AMPs are also histones and this is there job within the body. H2B is one that has been isolated from a frog and it's antimicrobial activity has been documented in many different organisms. These histones at as physiological barriers of the cell and many occur on the skin. I did not find anything about virus' so that would be interesting to see if it can kill or damage virus' as well as the known role in damaging bacterial cells and DNA/RNA
ReplyDeleteI know that histones are highy basic, though I can't say if that has anything to do with its anti-bacterial properties. In the idea of evolution, though, it is very interesting. Histones are the foundation of chromosomal DNA, whereas bacteria have circular DNA. Perhaps histones (being dangerous to bacterial cell types) were one of the early steps that led to differentiation of eukaryotic cell types from prokaryotic cell types? Just a thought :)
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