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Study uncovers the mechanism behind bacterial resistance

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A study led by scientists at the Research Institute at Nationwide Children’s Hospital uncovers why a certain bacterium that causes ear and respiratory infections eludes the immune system and causes chronic infections. The study, led by Kevin M. Mason, PhD, and Sheryl S. Justice, PhD, principal investigator in the Center for Microbial pathogenesis,  reveals new data on nontypeable Haemophilus influenzae ( NTHI ), the bacteria responsible for most  ear and throat infections.

Haemophilus influenzae is part of a family consisting of several strains, among which the most common is the type b, or Hib. In the past, Haemophilus influenzae was the leading cause of bacterial meningitis in children under 5 years, but with the introduction of Hib vaccine in 1985 , the incidence of this disease decreased significantly. But now NTHI is the leading cause of invasive infections in both adults and children.

 

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NTHI, should be noted, is part of commensal bacterial flora of the oropharynx, a microenvironment rich in heme -iron, a compound essential for the survival of the bacterium. NTHI creates problems when migrates to other regions such as the lungs or middle ear, where heme -iron is sequestered by immune system response. This is why researchers wanted to find out why NTHI can cause problems precisely where its development is not favorable microenvironment.

Researchers have learned how this bacterium manages to cause the immune system to work in his favor. It seems that with the first signs of  infection, there is a process called nutritional immunity, that is the immune response blocks the access to nutrients bacteria. The initial immune response triggers other events to fight off the infection such as the release of compounds that lead to inflammation (to isolate bacteria ) and migration of white blood cells to the site of infection, etc.

In an experiment that mimicked the immune response to NTHI infection in the middle ear, researchers observed that the serum  that contained compounds to kill bacteria, white blood cells and other agents, also  included heme -iron. When NTHI was re- exposed to heme -iron, suffered several changes, it became more elongated and divided more slowly. Because leukocytes were trained to target shorter rapidly dividing cells, NTHI infection went on.

This adaptation that is responsible for bacterial resistance to antibiotics prompted researchers to look for new ways to combat these infections. One method would be to use an inhibitor to block a critical pathway in the survival of bacteria. “If we could design a small molecule inhibitor that would look like heme-iron but would actually clog up a key metabolic pathway in bacteria, we may be able to get around the problem of antibiotic resistance,” suggests Dr. Mason.