Tag Archives: bacteria

Why People Often Get Sicker When They’re Stressed

Researchers at UT Southwestern Medical Center identified a receptor, known as QseE, which resides in a diarrhea-causing strain of E coli. The receptor senses stress cues from the bacterium’s host and helps the pathogen make the host ill. A receptor is a molecule on the surface of a cell that docks with other molecules, often signaling the cell to carry out a specific function.

Dr. Vanessa Sperandio, associate professor of microbiology at UT Southwestern and the study’’ senior author, said QseE is an important player in disease development because the stress cues it senses from a host, chiefly epinephrine and phosphate, are generally associated with blood poisoning, or sepsis.

“Patients with high levels of phosphate in the intestine have a much higher probability of developing sepsis due to systemic infection by intestinal bacteria,” Dr. Sperandio said. “If we can find out how bacteria sense these cues, then we can try to interfere in the process and prevent infection.”

Millions of potentially harmful bacteria exist in the human body, awaiting a signal from their host that it’s time to release their toxins. Without those signals, the bacteria pass through the digestive tract without infecting cells. What hasn’t been identified is how to prevent the release of those toxins.

“There’s obviously a lot of chemical signaling between host and bacteria going on, and we have very little information about which bacteria receptors recognize the host and vice versa,” Dr. Sperandio said. “We’re scratching at the tip of the iceberg on our knowledge of this.”

“When people are stressed they have more epinephrine and norepinephrine being released. Both of these human hormones activate the receptors QseC and QseE, which in turn trigger virulence. Hence, if you are stressed, you activate bacterial virulence.” Dr. Sperandio said the findings also suggest that there may be more going on at the genetic level in stress-induced illness than previously thought.

“The problem may not only be that the stress signals are weakening your immune system, but that you’re also priming some pathogens at the same time,” she said. “Then it’s a double-edged sword. You have a weakened immune system and pathogens exploiting it.”

Previous research by Dr. Sperandio found that phentolamine, an alpha blocker drug used to treat hypertension, and a new drug called LED209 prevent QseC from expressing its virulence genes in cells. Next she will test whether phentolamine has the same effect on QseE.

Full press release: Researchers probe mechanisms of infection

Scientists Target Bacteria Where They Live

Scientists Learning to Target Bacteria Where They Live

Scientists have learned that bacteria that are vulnerable when floating around as individual cells in what is known as their “planktonic state” are much tougher to combat once they get established in a suitable place — whether the hull of a ship or inside the lungs — and come together in tightly bound biofilms. In that state, they can activate mechanisms like tiny pumps to expel antibiotics, share genes that confer protection against drugs, slow down their metabolism or become dormant, making them harder to kill.

The answer, say researchers, is to find substances that will break up biofilms.
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Melander said “a throwaway sentence in an obscure journal” — the Bulletin of the Chemical Society of Japan — gave them another clue. They isolated a compound from the sponge that disperses biofilms and figured out how to synthesize it quickly and cheaply.
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But dispersing biofilms without understanding all the ramifications could be a “double-edged sword,” Romeo warned, because some bacteria in a biofilm could wreak worse havoc once they disperse.

“Simply inducing biofilm dispersion without understanding exactly how it will impact the bacterium and host could be very dangerous, as it might lead to spread of a more damaging acute infection,” he said.

Resurrection of the Human IRGM Gene

Interesting open access paper on Death and Resurrection of the Human IRGM Gene. Author summary:

The IRG gene family plays an important role in defense against intracellular bacteria, and genome-wide association studies have implicated structural variants of the single-copy human IRGM locus as a risk factor for Crohn’s disease. We reconstruct the evolutionary history of this region among primates and show that the ancestral tandem gene family contracted to a single pseudogene within the ancestral lineage of apes and monkeys.

Phylogenetic analyses support a model where the gene has been “dead” for at least 25 million years of human primate evolution but whose ORF became restored in all human and great ape lineages. We suggest that the rebirth or restoration of the gene coincided with the insertion of an endogenous retrovirus, which now serves as the functional promoter driving human gene expression. We suggest that either the gene is not functional in humans or this represents one of the first documented examples of gene death and rebirth.

Gram-negative Bacteria Defy Drug Solutions

Deadly bacteria defy drugs, alarming doctors by Mary Engel

Acinetobacter doesn’t garner as many headlines as methicillin-resistant Staphylococcus aureus, the dangerous superbug better known as MRSA. But a January report by the Infectious Diseases Society of America warned that drug-resistant strains of Acinetobacter baumannii and two other microbes — Pseudomonas aeruginosa and Klebsiella pneumoniae — could soon produce a toll to rival MRSA’s.

The three bugs belong to a large category of bacteria called “gram-negative” that are especially hard to fight because they are wrapped in a double membrane and harbor enzymes that chew up many antibiotics. As dangerous as MRSA is, some antibiotics can still treat it, and more are in development, experts say.

But the drugs once used to treat gram-negative bacteria are becoming ineffective, and finding effective new ones is especially challenging.
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For the most part, gram-negative bacteria are hospital scourges — harmless to healthy people but ready to infect already-damaged tissue. The bacteria steal into the body via ventilator tubes, catheters, open wounds and burns, causing pneumonia, urinary tract infections, and bone, joint and bloodstream infections.

Pseudomonas is widely found in soil and water, and rarely causes problems except in hospitals.

Searching for More Effective Tuberculosis Drugs

In India: A Search for More Effective Tuberculosis Drugs

The multi-drug regimen is a major problem for several reasons. It requires TB patients to manage taking four drugs exactly as prescribed over six to nine months. If patients don’t take the full course of the medicines, the TB bacteria may develop resistance to the drugs and become even more difficult to treat. To reduce that risk, many countries require that patients go to a clinic so a healthcare professional can watch them take the medication and ensure they are complying with their drug-treatment regimen. This is both expensive and time consuming. Gokhale said that a single drug that targets multiple pathways could save time and money by eliminating the need to take so many drugs over such a long period of time.

To create their new compound, Gokhale and his colleagues exploited an evolutionary quirk in the way Mycobacterium tuberculosis builds the lipid layer that coats its surface. Unlike other organisms, M. tuberculosis displays a suite of complex lipids on its outer membrane. Some scientists have suggested that these long lipid molecules contribute to the bacteria’s ability to maintain long-term infections by confusing the host’s immune system.

MRI That Can See Bacteria, Virus and Proteins

IBM team boosts MRI resolution

The researchers demonstrated this imaging at a resolution 100 million times finer than current MRI. The advance could lead to important medical applications and is powerful enough to see bacteria, viruses and proteins, say the researchers.

The researchers said it offered the ability to study complex 3D structures at the “nano” scale. The step forward was made possible by a technique called magnetic resonance force microscopy (MRFM), which relies on detecting very small magnetic forces.

In addition to its high resolution, MRFM has the further advantage that it is chemically specific, can “see” below surfaces and, unlike electron microscopy, does not destroy delicate biological materials.

Now, the IBM-led team has dramatically boosted the sensitivity of MRFM and combined it with an advanced 3D image reconstruction technique. This allowed them to demonstrate, for the first time, MRI on biological objects at the nanometre scale.

That is very cool.

New Family of Antibacterial Agents Discovered

Bacteria continue to gain resistance to commonly used antibiotics. In this week’s JBC, one potential new antibotic has been found in the tiny freshwater animal Hydra.

The protein identified by Joachim GrÃ¶tzinger, Thomas Bosch and colleagues at the University of Kiel (Germany), hydramacin-1, is unusual (and also clinically valuable) as it shares virtually no similarity with any other known antibacterial proteins except for two antimicrobials found in another ancient animal, the leech.

Hydramacin proved to be extremely effective though; in a series of laboratory experiments, this protein could kill a wide range of both Gram-positive and Gram-negative bacteria, including clinically-isolated drug-resistant strains like Klebsiella oxytoca (a common cause of nosocomial infections). Hydramacin works by sticking to the bacterial surface, promoting the clumping of nearby bacteria, then disrupting the bacterial membrane.

GrÃ¶tzinger and his team also determined the 3-D shape of hydramacin-1, which revealed that it most closely resembled a superfamily of proteins found in scorpion venom; within this large group, they propose that hydramacin and the two leech proteins are members of a newly designated family called the macins.

Source: American Society for Biochemistry and Molecular Biology

Bacteria Offer Line of Attack on Cystic Fibrosis

MIT researchers have found that the pigments responsible for the blue-green stain of the mucus that clogs the lungs of cystic fibrosis (CF) patients are primarily signaling molecules that allow large clusters of the opportunistic infection agent, Pseudomonas aeruginosa, to organize themselves into structured communities.
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P. aeruginosa appears as a classic opportunistic infection, easily shrugged off by healthy people but a grave threat to those with CF, which chokes the lungs of its victims with sticky mucus.

“We have a long way to go before being able to test this idea, but the hope is that if survival in the lung is influenced by phenazine — or some other electron-shuttling molecule or molecules — tampering with phenazine trafficking might be a potential way to make antibiotics more effective,” said Newman, whose lab investigates how ancestral bacteria on the early Earth evolved the ability to metabolize minerals.

How Antibiotics Kill Bacteria

Since the first antibiotics reached the pharmacy in the 1940s, researchers discovered that they target various pieces of machinery in bacterial cells, disrupting the bacteria’s ability to build new proteins, DNA, or cell wall. But these effects alone do not cause death, and a complete explanation of what actually kills bacteria after they are exposed to antibiotics has eluded scientists.
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The group found that all bactericidal antibiotics, regardless of their initial targets inside bacteria, caused E. coli to produce unstable chemicals called hydroxyl radicals. These compounds react with proteins, DNA, and lipids inside cells, causing widespread damage and rapid death for the bacteria.
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With the results of these two experiments, the researchers were able to identify three major processes implicated in gentamicin-induced cell death: protein transport, a stress response triggered by abnormal proteins in the cell membrane, and a metabolic stress response.

How Bleach Kills Bacteria

Developed more than 200 years ago and found in households around the world, chlorine bleach is among the most widely used disinfectants, yet scientists never have understood exactly how the familiar product kills bacteria. In fact, Hypochlorite, the active ingredient of household bleach, attacks essential bacterial proteins, ultimately killing the bugs.

“As so often happens in science, we did not set out to address this question,” said Jakob, an associate professor of molecular, cellular and developmental biology. “But when we stumbled on the answer midway through a different project, we were all very excited.”

Jakob and her team were studying a bacterial protein known as heat shock protein 33 (Hsp33), which is classified as a molecular chaperone. The main job of chaperones is to protect proteins from unfavorable interactions, a function that’s particularly important when cells are under conditions of stress, such as the high temperatures that result from fever.

“At high temperatures, proteins begin to lose their three-dimensional molecular structure and start to clump together and form large, insoluble aggregates, just like when you boil an egg,” said lead author Jeannette Winter, who was a postdoctoral fellow in Jakob’s lab. And like eggs, which once boiled never turn liquid again, aggregated proteins usually remain insoluble, and the stressed cells eventually die.

Jakob and her research team figured out that bleach and high temperatures have very similar effects on proteins. Just like heat, the hypochlorite in bleach causes proteins to lose their structure and form large aggregates.

These findings are not only important for understanding how bleach keeps our kitchen countertops sanitary, but they may lead to insights into how we fight off bacterial infections. Our own immune cells produce significant amounts of hypochlorite as a first line of defense to kill invading microorganisms. Unfortunately, hypochlorite damages not just bacterial cells, but ours as well. It is the uncontrolled production of hypochlorite acid that is thought to cause tissue damage at sites of chronic inflammation.

How did studying the protein Hsp33 lead to the bleach discovery? The researchers learned that hypochlorite, rather than damaging Hsp33 as it does most proteins, actually revs up the molecular chaperone. When bacteria encounter the disinfectant, Hsp33 jumps into action to protect bacterial proteins against bleach-induced aggregation.

“With Hsp33, bacteria have evolved a very clever system that directly senses the insult, responds to it and increases the bacteria’s resistance to bleach,” Jakob said.