Pneumonia drugs helped evolve a superbug

Microbe's genetic history charts its growing resistance to antibiotics and a vaccine

Sometimes natural selection gets a helping hand from humans. A new study tracing the genetic history of a nasty strain of pneumonia-causing bacteria shows that antibiotics and vaccines helped shape the microbe’s evolution.

In a technical tour de force, an international team of researchers deciphered the complete genetic blueprints of 240 samples of a strain of Streptococcus pneumoniae taken from sick people in 22 countries. The samples were isolated between 1984 and 2008, allowing researchers to see how the bacteria changed over time.

This strain of pneumonia, known as the Pneumococcal Molecular Epidemiology Network clone 1 or PMEN1, was first recognized in a hospital in Barcelona in 1984. But the new analysis indicates the strain probably first arose about 1970, the team reports in the Jan. 28 Science.

“When this clone emerged, it emerged into a world in which penicillin was frequently used,” says study coauthor Stephen Bentley, a molecular microbiologist at the Wellcome Trust Sanger Institute in Hinxton, England. Because the strain was not killed by penicillin, it had an advantage over strains that were susceptible and quickly spread.

S. pneumoniae is a common cause of death, especially among young children. A recent estimate published in the Lancet, for example, showed the bacteria caused 14.5 million cases of serious disease in children aged 1 to 5 worldwide in 2000, killing about 826,000. The PMEN1 strain contributes to these totals and, because of its resistance to several different antibiotics, has become a public health concern. The strain is considered a major cause of pneumonia, meningitis and other infections worldwide. The new study reveals some of the genetic tricks the organism used to develop drug resistance.

Since its emergence, the strain has changed one of its DNA letters about every 15 weeks, the analysis reveals. That rate of mutation is rapid but similar to rates seen in the deadly antibiotic-resistant Staphylococcus aureus bacteria commonly called MRSA.

The strain also occasionally swaps or recombines DNA with other bacteria, and such recombination may be far more important in developing drug resistance. Each DNA-swapping episode brings about 72 single-letter changes on average and sometimes introduces entirely new genes, or new versions of genes.

“Although it’s already got a winning formula for spreading around the globe, it’s constantly rearranging its DNA,” says Bentley. 

One way the bacterium evades the body’s immune system is by wrappingitself in a sugar coating called a polysaccharide capsule. The PMEN1 strain’s capsule is designated serotype 23F to distinguish it from other capsules that use slightly different sugars. The capsule is also one target of a vaccine called PCV7, first introduced in 2000.

But the new analysis shows the pneumonia bacteria were already ahead of vaccine makers. By the time the vaccine hit clinics, a small number of pneumonia bacteria had already swapped DNA with other bacteria and changed their sugar coats to serotype 19A. That switch probably happened in the United States around 1996 and independently in Spain in 1998. When the vaccine was introduced, it drastically reduced the number of infections with bacteria coated in the 23F capsule, leaving the field clear for 19A infections to take over. Newer versions of the vaccine target more types of capsules.

The study “illustrates that these genes are under enormous selection pressure due to human interference with antibiotics and vaccines,” says Garth Ehrlich, a bacterial pathologist at the Allegheny-Singer Research Institute in Pittsburgh. Mapping the organism’s past genetic contortions may not help researchers predict what the bacteria will do next, but the analysis shows that some genes are particularly prone to changes and probably are not good vaccine targets, he says.

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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