It's been with humanity since before modern humans started to leave Africa, beguiling immune systems and stubbornly persisting in human stomachs for more than 60,000 years. It doesn't always trigger illness, but, when it does, it can cause crippling stomach ulcers and gastritis.
When Helicobacter pylori invades a new host, it pulls off a frenetic feat of rapid-fire evolution that science is only just beginning to comprehend. It's a bacterial trick that's thought to have helped the widespread pathogen stay ahead of humans' natural defense systems—possibly since humans became human.
A new H. pylori infection triggers an immune response that leads to stomach inflammation, attracting white blood cells to the stomach lining and releasing reactive nitrogen- and oxygen-based molecules. These molecules can trigger mutations in the bacterial genes, helping the species accelerate its rate of evolution as it comes under attack. And new research published in Nature Communications has revealed just how quickly the bacteria evolves during this initial battle.
"This extraordinarily fast mutation rate during the acute infection phase is the highest mutation estimate so far for any bacteria."
Researchers somehow found two infected Australian volunteers—both naturally infected with H. pylori—who were willing to be treated with potent antibiotic cocktails, then re-infected by drinking beef broth tainted with strains of the bacteria that were harvested from their own bodies prior to the antibiotic treatment. All the while, the volunteers were subjected to repeated endoscopies that sampled bacteria and checked for inflammation. That was certainly brave of the two volunteers, but the researchers would have preferred to have found more of them. So an unfortunate rhesus macaque was subjected to similar tests. The scientists analyzed the germ's DNA at a laboratory in Pennsylvania to figure out how quickly it was mutating during different stages of infection.
During an initial evolutionary burst following a new infection, the bacterial DNA was found to mutate at 40 to 50 times the average rate at which it mutated during the subsequent chronic infection. All of the bacterial DNA mutated quickly during this evolutionary burst, but the changes manifested most prominently in the cell's outer membrane proteins, helping them avoid detection by human defense cells. The mutation burst was detected both during the initial infections of the monkey and the re-infections of the human volunteers.
(Chart: Nature Communications)
"This extraordinarily fast mutation rate during the acute infection phase is the highest mutation estimate so far for any bacteria, exceeding the substitution rate in other bacterial species by at least two orders of magnitude," the researchers write in their paper—noting that similar experiments have not yet been conducted during the initial infection stages of other bacterial pathogens.
Bodo Linz, a research associate at Pennsylvania State University who was involved with the study, doesn't expect these findings alone to lead to any new therapies. But he said the results could help do that in the long run.
"It's basic research on which we can build for future studies," Linz says. "We need to understand what's going on before we can develop immune therapy or prevention."