Further study may help make biomedical devices safer and explain urinary tract infections
The Cell paper shows how force stretches FimH. The active site is green, and the force stretches the segment that connects to the rest of the bacteria, in pink.
Researchers at the University of Washington have learned that something most people take for granted is not true: that the force of fluids within the human body helps to break the adhesive bonds of invasive bacteria and counterbalance infection.
Most scientists as well as lay people assume, for example, that a sneeze helps clear infection, or that urine helps to clear bacteria from the urinary tract.
"We need to know how bacterial adhesion is altered by shear," says another author, Dr. Viola Vogel, director of the University of Washingtons Center for Nanotechnology in the Department of Bioengineering. "The most amazing part of this is that conventional wisdom says that bacteria have a more difficult time adhering to surfaces when they are subjected to shear force – whether the bacteria are in the intestines, in the urinary tract or in biomedical implants. This paper explains how bacteria firmly adhere to surfaces under shear flow, which is remarkable."
Other authors of the paper include Wendy E. Thomas, of the UW Department of Bioengineering, Dr. Elena Trintchina of the Department of Microbiology and Manu Forero of the Department of Physics.
"This is a fairly startling concept," says Dr. Harry L.T. Mobley, professor of microbiology and immunology at the University of Maryland School of Medicine. He is not an author of the paper. "This describes a protein that sticks to things. Usually, we think of a protein either sticking to something or not sticking to something. Here we see a protein binding tighter when it is trying to be sheared off. That opens the door to further investigation."
Presently, most research operates on the assumption that shear stress reduces the lifetime of a receptor bond. However, the paper in Cell suggests that the force might be exactly what it takes to get the bacteria to adhere.
"Bacterial adhesion has been described for a century – bacteria need to adhere in order to colonize," Sokurenko says. "Its taken a century before weve been able to understand what happens once you see the bacteria clump red blood cells. What happens is that the bacteria and blood cells start to separate after you stop shaking. Then, if you shake them again, they clump again. The moment shear starts pushing them away from the surface, the bacteria adhere tightly. It demonstrates an amazing flexibility by infectious bacteria and provides a mechanism for bacteria to resist the effects of free-flowing inhibitor molecules that can block the adhesion."
In other words, E. coli appears designed to colonize parts of the body that are exposed to a lot of shear force. It has hair-like protrusions, fimbriae, (with the FimH protein on their tips) that touch the nearby surface, detect the dragging force, and set off a chain of molecular events that cause it to cling more effectively.
The computationally derived insights of how the switch works were tested by using genetic approaches to change individual amino acids on FimH. Thomas and Vogel developed a structural model using steered molecular dynamic simulations describing how mechanical force switches the adhesion strength of FimH from low to high.
"Its quite remarkable, because this force-induced switching is happening at the tip of fimbriae along distance away from the cell membrane," Thomas says. "It makes you wonder how many more proteins exist that are switched mechanically – that is a fascinating area for research."
"We need to know how bacterial adhesion is altered by shear. FimH is the second adhesion protein, after fibronectin, for which we have established a structural mechanism for how nature uses mechanical force to regulate protein function. These adhesion proteins thus serve as nanoscale switches that convert mechanical stimuli into a chemical response," Vogel says
The forces described in the paper are within the range of shear force found within the body.
UWs Departments of Microbiology and Bioengineering do considerable research on bacterial adhesion and biomedical devices, respectively.
"A lot of bacteria have been studied under static conditions. What this paper should alert people to is that force profoundly affects the behavior of bacteria and their ability to bind to target cells," Vogel says.
For a video of bacterial movement during flow, see http://www.washington.edu/newsroom/news/images/lotohi.avi The video shows how E. coli moves around on while surrounded by low flow, but then locks down and grips its current position when heavy flow is present.
http://www.washington.edu/newsroom/news/images/fimhB.jpg The Cell paper shows how force stretches FimH. The active site is green, and the force stretches the segment that connects to the rest of the bacteria, in pink.
Walter Neary | EurekAlert!
Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur
MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy