News Release: Research , School of Medicine , School of Public Health

Jan. 27,  2011

Genomics Reveals How Pneumonia Bacteria Evolve to Evade Antibiotics and Vaccines

News Article ImageS. pneumoniae, or pneumococcus. (Image Courtesy CDC)

New genomic research makes it possible to see how a common type of pneumonia bacteria has evolved in response to antibiotics and vaccines over the last few decades.

The results were published online Jan. 27 by the journal Science.

“Drug resistant forms of S. pneumoniae first came onto the radar in the 1970s,” says senior author Stephen Bentley, PhD, from the Wellcome Trust Sanger Institute in Cambridge, UK. “We sequenced 240 samples collected over the course of 24 years from the PMEN1 lineage of S. pneumoniae. By comparing the sequences, we can begin to understand how this bacterium evolves and reinvents itself genetically in response to human interventions.”

An international team of scientists participated in the study, including researchers from the United Kingdom, the United States, Germany, Canada, Denmark, South Korea, South Africa and Vietnam. The 240 strains studied were closely related strains that come from Europe, South Africa, America and Asia and are resistant to several antibiotics.

“A big part of the story is the extraordinary diversity in the bacterial genome,” says co-author Keith Klugman, MD, PhD, professor of global health at Emory University’s Rollins School of Public Health. “This comes from S. pneumoniae’s ability to take up and integrate DNA from its neighbors. We knew it was possible, but the extent is surprising.”

S. pneumoniae (the pneumococcus) is a bacterium often found at the back of the human nose, even in healthy people. Most people have been carriers at some point in their lives. In the United States, it is the most common cause of pneumonia, meningitis, blood stream infections and middle ear infections in young children.

Public health authorities have been concerned about the spread of S. pneumoniae varieties that are resistant to antibiotics. In 2000, a vaccine against seven varieties of S. pneumoniae was introduced and made standard for children in many countries. However, disease caused by varieties not covered by the vaccine has been increasing over the last decade.

Klugman is also professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine and a visiting researcher at the Centers for Disease Control and Prevention in Atlanta. He has a research unit at the University of the Witwatersrand in Johannesburg, South Africa.

Most of the genetic diversity in this bacterium comes from its ability to take up DNA from outside the cell, the scientists found. If the bacterial genome is analogous to a book, most of the changes took place “horizontally,” via pasting in entire new pages from other bacteria, rather than “vertically,” through errors in copying that change one word at a time.

Almost three-quarters of the length of the bacterial genome has been shuffled or replaced in at least one of the strains studied. The S. pneumoniae genome size is roughly two million base pairs (letters) or around 1,500 times smaller than the human genome, and on average, a few percent of the genome has been shuffled or replaced in each strain.

“I think we’ve arrived at the point where the standard of how you identify a bacterial strain in this species has shifted to whole genome sequencing,” Klugman says.

By the previous standard of MLST (multi-locus sequence typing) involving seven genes, many of the strains studied would be considered the same – yet they are different in important ways, he says.

“In the future, sequencing of whole bacterial genomes will offer insight into the range of strategies that bacteria are able to use to evade human interventions for treatment and prevention,” he says.

The scientists were able to construct an evolutionary tree for the various S. pneumoniae strains, and found that the patterns of responses in their DNA look different when comparing the responses to antibiotics and vaccines. Resistance to antibiotics such as the widely used azithromycin comes from the bacteria importing new genes that can block their effects or cause them to be pumped out of the cell. Resistance to other antibiotics can come as the result of an alteration in one place of the DNA that encodes a particular enzyme.

The responses to vaccination have been different, the scientists found. Vaccines push the human immune system to make antibodies that target the bacterium’s outer capsule. The scientists saw big changes or even rearrangements in several genes that encode components of the outer capsule.

“We inferred that the vaccine effectively wipes out the existing population of bacteria and allows variants that can escape the vaccine to take over,” Klugman says.

The research was supported by the Wellcome Trust.


The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.

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Twitter: @emoryhealthsci

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