When the body senses an infection, one of the first lines of defense is to send immune molecules called host-derived antimicrobial peptides (AMPs) to target and kill bacteria. However, bacteria have learned to resist AMPs through a series of countermeasures such as remodeling their outer membrane surface to be less permeable. Nontypeable Haemophilus influenzae (NTHI) is such a bacterium.
NTHI resides in the human upper airway, typically without causing any harm. However, NTHI has the ability to change from a non-harmful bacterium to a disease causing pathogen, responsible for pink eye, sinusitis, middle ear infection and complications of cystic fibrosis. "When transitioning to a harmful pathogen, NTHI defends against increased production of AMPs by using the Sap, which stands for sensitivity to antimicrobial peptides, proteins to arm against attack, " said Kevin M. Mason, PhD, principal investigator in the Center for Microbial Pathogenesis at The Research Institute at Nationwide Children's Hospital and lead study author. "Yet, it's unclear just how the Sap transporter complex provides protection against AMPs."
To help explain the mechanisms that NTHI uses to protect itself from AMPs, Dr. Mason's team examined an animal model of middle ear infection. They had previously shown that NTHI bacteria lacking the protein SapA were susceptible to AMP attack. In the study, they describe the Sap transporter system that recognizes and transports host immune defense molecules into the bacterial cell. This system is necessary for the bacteria to survive in the host.
"It seems that NTHI senses the presence of these immune molecules, steals them from the host and arms itself to protect against future attacks," said Dr. Mason. "NTHI imports AMPs into the bacterial cell and then degrades them in the interior of the cell. By remodeling its membranes, the bacterium appears as already attacked, which protects it from being bothered by additional AMPs. Basically, transporting AMPs acts as a counter strategy to evade innate immune defense and ultimately benefits the bacterium nutritionally." This study provides the first direct evidence that the protein SapA contributes to bacterial survival by providing protection from AMPs in the host.
Dr. Mason says that targeting the Sap transport system may provide a way to use AMP derivatives as alternatives to antibiotics to treat NTHI infections. "Our long-range goal is to block this uptake system and starve the bacterium of essential nutrients. If we could develop a small molecule inhibitor that could block binding and transport, we could render NTHI susceptible to immune attack, while preserving the body's normal bacteria that are often disrupted by conventional antibiotic use."
For more information about Dr. Kevin Mason, visit http://www.nationwidechildrens.org/kevin-mason
For more information about the Center for Microbial Pathogenesis, visit http://www.nationwidechildrens.org/microbial-pathogens
Erin Pope | EurekAlert!
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Separate brain systems cooperate during learning, study finds
22.02.2018 | Brown University
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
22.02.2018 | Life Sciences
22.02.2018 | Physics and Astronomy
22.02.2018 | Earth Sciences