Published December 12, 2012
UB microbiologists studying bacterial colonization in mice have discovered how the bacteria associated with pneumonia, middle ear infections and other illnesses acquire and spread resistance.
The research team, led by Anders
Hakansson, PhD, found that antibiotic resistance in
Streptococcus pneumoniae stems from the transfer of DNA between
bacterial strains in biofilms in the nasopharynx, the area just
behind the nose.
In a study published in mBio, the UB researchers noted that the genetic exchange of antibotic resistance occurs about 10 million times more effectively in animals’ noses than in their blood—an efficiency far higher than they expected.
“The high efficiency of genetic transformation that we
observed between bacteria in the nose has a direct clinical
implication, since this is how antibiotic resistance
spreads—and it’s increasing in the population,"
explains Hakansson, lead author and an assistant professor of microbiology and
“The bacteria ‘borrow’ each others’ DNA in order to become more fit in the host environment and more elusive to the actions of antibiotics.”
Hakansson performed the study with co-authors Laura R. Marks, an MD/PhD candidate, and Ryan M. Reddinger, a PhD candidate.
Exactly how bacteria acquire and spread resistance in the individuals carrying them is not well established for most bacterial organisms.
Hakansson’s research, however, opens a new lead into the mysteries of bacterial organization during colonization, and how this organization promotes antibiotic spread and the evolutionary fitness of Streptococcus pneumoniae.
A major colonizer, Streptococcus pneumoniae—also known as
pneumococcus—is a leading cause of morbidity and mortality
from respiratory tract and invasive infections in children and the
“It’s rampant in daycare centers and the cause of
many children’s ear infections,” Hakansson says of the
pathogen, which essentially everyone carries in their nasopharynx
by about age 1.
“In developing countries, where fresh water, nutrition and antibiotics are lacking, it is a major cause of disseminating pneumonia leading to sepsis and death of about a million children worldwide, often in combination with virus infections, such as the flu.”
In earlier research, Hakansson and his collaborators showed that pneumococci form sophisticated, highly structured biofilm communities when they colonize the nose. These biofilms protect against the action of antibiotics, which have a hard time destroying them.
“In addition, we know that some of the bacteria have to die in order to develop good biofilms,” Hakansson says. “So, dead bacteria help create good biofilms and provide DNA that other bacteria can take up and use, which is how bacteria spread antibiotic resistance and become more fit.”
The current research shows that specifics aspects of the nasopharyngeal environment—including lower temperature, limited nutrient availability and epithelial cell interaction—create ideal conditions for these phenomena to occur.
The UB researchers reconstituted this environment in vitro by growing bacterial biofilms on top of human bronchial carcinoma cells or epithelial cells from healthy individuals provided by G. Iyer Parameswaran, MD, research assistant professor of medicine.
Until now, Hakansson says, no studies have explored how
antibiotic resistance spreads in the environment where it takes
Frederick Griffith, who was studying Streptococcus pneumoniae because of its role in the Spanish flu epidemic, first described the natural transformation of DNA in infected mice in 1928.
Genetic transformation also helped identify DNA as the hereditary material and thus figured in the milestone research of James D. Watson and Francis Crick in determining DNA’s structure.
“Since then,” Hakansson notes, “all
experiments with pneumococcal transformation have been done
artificially in test tubes or in blood infection models, even
though it's known epidemiologically that genetic exchange occurs
almost exclusively when the organism exists in the
The UB team is now working to develop clinical applications for their findings with the goal of better treating and prevent infections, especially with resistant organisms—from children’s ear infections to community and hospital-acquired pneumonia in the elderly that can lead to lethal septicemia.
There’s an increasing need to find ways to fight antibiotic-resistant bugs, they note: the FDA has only some 15 antimicrobials in its development pipeline.