Secret of surviving sepsis, say scientists
Infection is a complicated process. Every day, we're all carrying organisms that have the potential to kill someone. A recent article in the Journal of Infectious Diseases, for example, found that just under a third of us are colonized with Staphylococcus aureus, a leading cause of skin and soft tissue infections. From our noses, to our mouth, to our gut and elsewhere, we are literally teeming with organisms--so much so that, by the numbers, the cells in our body are more bacterial than human. But generally, we don't get sick. When epidemiologists investigate infectious disease, we consider a number of factors: the genetics of the pathogenic organism; the genetics of the host; environmental and cultural factors; host nutritional status; host immune status; and a plethora of other specifics which may affect development of disease. Still, when we discuss host genetics, we've mostly been looking at nuclear genes: those on our 23 pairs of chromosomes. An interesting study out in The Lancet today suggests that view is too narrow. Recall that within our cells are organelles, each with a specialized function. One such organelle is the mitochondria, the "power plant" of the cell. Much evidence has been put forth that suggests these organelles evolved from bacteria, engulfed by primitive eukaryotic cells. As such, these organelles have their own DNA, separate from that in our nucleus. Differences in this mitochondrial DNA (mtDNA) has been previously shown to affect sperm motility, and to affect the risk of individuals for development of some late-onset neurodegenerative diseases. However, the current study looks at how differences in mtDNA can affect survival after sepsis (bacterial infection of the bloodstream).
Variations in the mtDNA were previously studied by the authors of the current study. By investigating single nucleotide polymorphisms (SNPs) in the mtDNA, they grouped people by mtDNA haplogroup (10 different ones were identified). Don't get confused with the terminology--basically, they just looked at changes, and grouped people together using the differences they found. One of these groups--haplogroup H--was found to be most common in their study population (41.3% of the population). They wanted to see if this had any bearing on survival after sepsis--if haplogroup H people survived more often than their non-haplogroup-H neighbors.
And, yep, indeed they did. Haplogroup H folks showed higher survival over 180 days than those without the haplogroup, and were a bit over 2 times more likely to survive to that point than those in other mtDNA haplogroups. They were also found to generate "a significantly higher core temperature" than those in other haplogroups--in other words, on average, they spiked higher fevers. This might sound like a bad thing, but a fever is actually one of the body's elegant defenses against infection: the increase in body temperature can slow the growth of , or even kill, some bacterial pathogens. Additionally, the increase in temperature also increases the rate of enzymatic reactions, increasing metabolism and speeding tissue repair. (The fever response is also one that's incredibly conserved, from an evolutionary standpoint. Even ectotherms--"cold-blooded" animals--create a "fever" by basking in the sun during an infection). It's not known if this higher fever temperature is the key to the differential survival in the groups, but it's an intriguing finding. It's also interesting to note that, though haplogroup H is the most common in the population, it's the most recently evolved. Could it have been selected for due to this, and potentially other, effect on infection mortality? Infectious disease has certainly played a role in shaping our genomes--for example, sickle cell carriers who are more resistant to malaria; or cystic fibrosis carriers who are more resistant to typhoid. This may be yet another example.
It should be noted that this was a fairly small pilot study--150 people were enrolled, so larger studies will be needed to see if this finding is repeated, and if so, just what the mechanism is that renders them more likely to survive. Definitely food for thought, and a reminder of yet another level of complexity to consider for those of us who seek to sort these kinds of things out.
