The collaborative research -- led by Phillip Klebba, professor and head of the department of biochemistry -- clarifies how microorganisms colonize animal hosts and how scientists may block them from doing so. The findings suggest new approaches against bacterial disease and new strategies for antibiotic development.
The study -- in collaboration with Tyrrell Conway, director of the Microarray and Bioinformatics Core Facilities at the University of Oklahoma, and Salete M. Newton, Kansas State University research professor of biochemistry -- recently appeared in PLOS ONE. It shows how iron acquisition affects the ability of bacteria to colonize animals, which is the first stage of microbial disease.
"This paper establishes that iron uptake in the host is a crucial parameter in bacterial infection of animals," said Klebba, the senior author on the publication. "The paper explains why discrepancies exist about the role of iron, and it resolves them."
Iron plays a key role in metabolism, leading bacteria and animals to battle each other to obtain it. Klebba's team found that E. coli must acquire iron from the host to establish a foothold and colonize the gut -- a concept that was often debated by scientists.
"For years it was theorized that iron is a focal point of bacterial pathogenesis and infectious disease because animals constantly defend the iron in their bodies," Klebba said. "Animal proteins bind iron and prevent microorganisms from obtaining it. This is called nutritional immunity, and it's a strategy of the host defense system to minimize bacterial growth. But successful pathogens overcome nutritional immunity and get the iron."
Little was known about what forms of iron enteric bacteria -- which are bacteria of the intestines -- use when growing in the host, but this study shows that the native Gram-negative bacterial iron uptake systems are highly effective. Scientists questioned whether prevention of iron uptake could block bacterial pathogenesis. This article leaves no doubt about the importance of iron when E. coli colonizes animals because bacteria that were systematically deprived of iron became 10,000-fold less able to grow in host tissues, Klebba said.
"This is the first time our experiments unambiguously verified the indispensability of iron in infection, because here we created the correct combination of mutations to study the problem," Klebba said.
Enteric bacteria have so many iron transport systems that it's difficult to eliminate them all. For example, E. coli has at least eight iron acquisition systems.
"These transporters are redundant because iron is essential," Klebba said. "Bacteria are resilient. If one system is blocked, then another one takes over."
These findings suggest strategies to block microorganisms from creating diseases in animals and humans, including the potential for antibiotic development and for therapeutic antibodies.
"It gives us insight," Klebba said. "Now we know that iron deprivation protects against disease, but we must be comprehensive and inhibit multiple systems to completely shut down the microorganisms' ability to obtain the metal."
The researchers are using their findings to isolate antibodies that block bacterial iron uptake. This may help animals and humans defend themselves against microbial diseases.
"We would like to apply this research and protect people from bacterial infection," Klebba said. "That's one of the focal points of our laboratory."
Klebba's research was supported by a $1.25 million grant from the National Institutes of Health.
The study was led by Hualiang Pi, Klebba's student at his former institution, the University of Oklahoma. Another Kansas State University collaborator on the project was Lorne Jordan, doctoral student in biochemistry, Toledo, Ohio.
The PLOS ONE article, by Hualiang Pi et al., -- titled "Role of Catecholate Siderophpores in Gram-negative Bacterial Colonization of the Mouse Gut" -- is available at http://dx.plos.org/10.1371/journal.pone.0050020.
Phillip Klebba, 785-532-6121, firstname.lastname@example.org
Phillip Klebba | Newswise
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy