June 28, 2018 7:00 AM

A Common Bacterium’s Weapon System Tied to Its Adaptability

The battle for survival makes pneumococcus a formidable foe.

As many parents with young children can attest, day care centers are incubators of disease. While the little ones are busy playing with blocks and making friends, a bug known as Streptococcus pneumoniae is busy building a kingdom inside their tiny noses.

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According to the Centers for Disease Control and Prevention, before the introduction of the pneumococcal conjugate vaccine in 2010, the bacteria accounted for an estimated 5 million middle ear infections each year in children younger than 5. Streptococcus pneumoniae, also known as pneumococcus, can also be deadly, leading to severe pneumonia or bacterial meningitis.

“Streptococcus pneumoniae is an interesting pathogen because its major weapon to continue to cause disease in humans throughout thousands of years is its incredible ability to adapt its genome,” says Suzanne Dawid, M.D., Ph.D., an infectious disease specialist in the University of Michigan Medical School Department of Pediatrics and co-author of a new paper in the Proceedings of the National Academy of Sciences.

She notes that while the vaccine is very good, it covers only 13 of the more than 90 strains of the bacteria. Dawid and her colleagues are seeking to understand how the bacteria is able to adapt so readily. The answer appears to involve a complex system of bacterial warfare.

When neighbors attack

Pneumococcus is like a scavenger in the sense that, when necessary, it can scoop up free-floating DNA from its environment.

“The organism uses a huge number of genes to control the system that allows it to take up DNA from its environment. This system is highly regulated and is not on all the time,” Dawid explains. Researchers have observed this system, known as competence, for more than 100 years. In fact, in the early 1900s, scientists studying changes in pneumococcus bacteria discovered that DNA is inherited.

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In the new paper, Dawid and co-author Charles Wang, an M.D./Ph.D. student in Dawid’s lab, found a connection between the competence system and a system that allows the bacteria to secrete antimicrobial substances, or peptides, to attack neighboring strains for their DNA.

When looking at the genes that encode for the antimicrobial peptides, they noticed something interesting. Three-quarters of the bacterial strains they studied had the genes to make antimicrobial peptides but didn’t seem to be able to use them.

“These strains had a nonfunctional version of a protein required to transport them out of the cell. This didn’t make sense because you have to get the peptides out of the cell in order for them to kill other bacteria,” she notes. The remaining quarter of strains had the full system intact and could kill other bacteria at any time.

“Every population of strains we looked at, from colonized individuals in day care settings to other collections in other cities and even isolates from South Africa, had the same 75/25 percent split,” Dawid says.

Wang and Dawid knew the majority of strains had to be making the peptides for a reason. They found that when these bacteria turned on their competence system to take up DNA, the weaponized peptides were able to escape the cell through the same transporter before the system was quickly turned off again.

The question remains: If most strains of pneumococcus turn on competence only once in a while, why don’t the more aggressive strains take over? Dawid’s group hypothesizes that constant attacks must come at a cost, depleting the bacteria’s resources. Most strains make the peptides only when necessary and secrete them only during brief periods when competence is turned on.

This life-and-death battle is constant — as strains attack, adapt and defend themselves — and has been playing out for thousands of years.

“We figure bacteria have probably figured out the ideal target for killing other members of their same species,” remarks Dawid. “It would be silly not to try to use some of these strategies to develop new therapeutics.”