An in-depth genetic analysis of closely related strains of streptococcus pneumoniae, the bacterium that causes pneumonia, has revealed how the microbe has continually escaped attempts to defeat it. The findings show that the bug can easily swap chunks of DNA with other strains, allowing it to rapidly evolve defenses against both antibiotics and vaccines. Researchers say the findings will help them design more effective preventive measures and treatments.
“It shows just how astonishingly quickly this bug can reinvent itself,” says William Hanage, associate professor of epidemiology at Harvard and one of the study’s authors. “I think the findings should renew our recognition of exactly how innovative we have to be in finding new ways to combat disease caused by this organism, which is readily capable of throwing off any intervention we direct against it.”
Despite antibiotics and a vaccine, the World Health Organization estimates that pneumonia-causing bacteria, known as pneumococcus, is responsible for about four million deaths per year, mostly among children from poor countries.
Researchers sequenced 240 strains of a drug-resistant form of the microbe, collected between 1984 and 2008 from 22 countries around the globe. The original variant, from which the others descended, is thought to have arisen about 40 years ago in response to the introduction of antibiotics. While researchers had previously compared a handful of genes in these microbes, this study was the first to analyze the entire genome, allowing researchers to re-create its evolutionary tree. The findings are published today in the journal Science.
“I think this is a landmark paper,” says Alexander Tomasz, professor of microbiology at the Rockefeller University. Tomasz contributed some of the DNA used in the study. “It uses the most sophisticated molecular techniques on [strains] collected at various sites over time to trace the evolution of one of the most important human pathogens.”
Microbes can evolve in two ways; via single letter changes to the gene-coding region of DNA, or by swapping large chunks of DNA. The latter mechanism occurs less frequently, but it is capable of producing much larger changes in the organism—including the ability to evade a vaccine.
The new research highlights just how common this swapping is in the pneumococcus bacteria. “We can see multiple occasions where the clone has acquired different elements of resistance, such as to macrolide antibiotics, at different times and in different parts of the world,” says Stephen Bentley, a scientist at the Wellcome Trust Sanger Institute, and the senior author of the study.
The researchers found, for example, two variants that had swapped out the portions of their genomes that made them vulnerable to the vaccine. “That kind of convergent evolution in parallel tells us something about how readily these things can pick up the opportunity to escape,” says Hanage. “We’ve known for years that it happens. What we hadn’t realized was just how many times it occurs in individual lineages.” The most recent version of the vaccine has already been updated to include antibodies against these strains.