bacteria

to-kill-the-competition,-bacteria-throw-pieces-of-dead-viruses-at-them

To kill the competition, bacteria throw pieces of dead viruses at them

bacteria, Biology, evolution, phages, Science / /

Murderous —

A network of mutual murder ensures that diverse populations of bacteria survive.

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A green, lawn like background with an orange item consisting of legs, a narrow shaft, and a polygonal head.

Enlarge / This is an intact phage. A tailocin looks like one of these with its head cut off.

Long before humans became interested in killing bacteria, viruses were on the job. Viruses that attack bacteria, termed “phages” (short for bacteriophage), were first identified by their ability to create bare patches on the surface of culture plates that were otherwise covered by a lawn of bacteria. After playing critical roles in the early development of molecular biology, a number of phages have been developed as potential therapies to be used when antibiotic resistance limits the effectiveness of traditional medicines.

But we’re relative latecomers in terms of turning phages into tools. Researchers have described a number of cases where bacteria have maintained pieces of disabled viruses in their genomes and converted them into weapons that can be used to kill other bacteria that might otherwise compete for resources. I only just became aware of that weaponization, thanks to a new study showing that this process has helped maintain diverse bacterial populations for centuries.

Evolving a killer

The new work started when researchers were studying the population of bacteria associated with a plant growing wild in Germany. The population included diverse members of the genus Pseudomonas, which can include plant pathogens. Normally, when bacteria infect a new victim, a single strain expands dramatically as it successfully exploits its host. In this case, though, the Pseudomonas population contained a variety of different strains that appeared to maintain a stable competition.

To learn more, the researchers obtained over 1,500 individual genomes from the bacterial population. Over 99 percent of those genomes contained pieces of virus, with the average bacterial strain having two separate chunks of virus lurking in their genomes. All of these had missing parts compared to a functional virus, suggesting they were the product of a virus that had inserted in the past but had since picked up damage that disabled them.

On its own, that’s not shocking. Lots of genomes (including our own) have plenty of disabled viruses in them. But bacteria tend to eliminate extraneous DNA from their genomes fairly quickly. In this case, one particular viral sequence appeared to date back to the common ancestor of many of the strains since all of them had the virus inserted at the same location of the genome, and all instances of this particular virus had been disabled by losing the same set of genes. The researchers termed this sequence VC2.

Many phages have a stereotypical structure: a large “head” that contains their genetic material, perched on top of a stalk that ends in a set of “legs” that help latch on to their bacterial victims. Once the legs make contact, a stalk contracts, an action that helps transfer the virus’ genome into the bacterial cell. In VC2’s case, all copies of it lacked the genes for producing the head section, as well as all the genes needed for processing its genome during infection.

This made the researchers suspect VC2 was something called a “tailocin.” These are former phages that have been domesticated by bacteria so they can be used to harm the bacteria’s potential competition. Bacteria with a tailocin can produce partial phages that consist only of the legs and stalk. These tailocins can still find and latch on to other bacteria, but when the stalk contracts, there’s no genome to inject. Instead, this just opens a hole in the membrane of their victim, partially eliminating the boundary of the cell and allowing some of its contents to leak out, leading to its death.

An evolutionary free-for-all

To confirm that the VC2 sequence encodes a tailocin, the researchers grew some bacteria that contained the sequence, purified proteins from it, and used electron microscopy to confirm that they contained headless phages. Exposing other bacteria to the tailocin, they found that while the strain that produced it was immune, many other strains growing in the same environment were killed by it. When the team deleted the genes that encode key parts of the tailocin, the killing went away.

The researchers hypothesize that the system is used to kill off potential competition but that many strains have evolved resistance to the tailocin.

When the researchers did a genetic screen to identify resistant mutants, they found that resistance was provided by mutations that interfered with the production of complex sugar molecules that are found on proteins that end up on the exterior of cells. At the same time, most of the genetic differences among the VC2 genes occur in the proteins that encode the legs, which latch on to these sugars.

So it appears that every bacterial strain is both an aggressor and a victim, and there’s an evolutionary arms race that leads to a complex collection of pairwise interactions among the strains—think of a rock/paper/scissors game with dozens of options. And the arms race has a history. Using old samples, the researchers show that many of the variations in these genes have been around for at least 200 years.

Evolutionary competitions are often viewed as a simple one-against-one fight, probably because it’s an easy way to think about them. But the reality is that most are more akin to a chaotic bar room brawl—one where it’s rare for any faction to obtain a permanent advantage.

Science, 2024. DOI: 10.1126/science.ado0713  (About DOIs).

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Nitrogen-using bacteria can cut farms’ greenhouse gas emissions 

agriculture, bacteria, Biology, climate change, fertilizer, nitrogen, Science / /

Keeping crops from the greenhouse —

Nitrogen fertilizers get converted to nitrous oxide, a potent greenhouse gas.

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A tractor amidst many rows of small plants, with brown hills in the background.

Fritz Haber: good guy or bad guy? He won the Nobel Prize in Chemistry in 1918 for his part in developing the Haber-Bosch process, a method for generating ammonia using the nitrogen gas in air. The technique freed agriculture from the constraint of needing to source guano or manure for nitrogen fertilizer and is widely credited for saving millions from starvation. About half of the world’s current food supply relies on fertilizers made using it, and about half of the nitrogen atoms in our bodies can be traced back to it.

But it also allowed farmers to use this newly abundant synthetic nitrogen fertilizer with abandon. This has accentuated agriculture’s role as a significant contributor to global warming because the emissions that result from these fertilizers is a greenhouse gas—one that has a warming potential almost 300 times greater than that of carbon dioxide and remains in the atmosphere for 100 years. Microbes in soil convert nitrogen fertilizer into nitrous oxide, and the more nitrogen fertilizer they have to work with, the more nitrous oxide they make.

Agriculture also leaks plenty of the excess nitrogen into waterways in the form of nitrate, generating algal blooms that create low-oxygen ‘dead zones’ where no marine life can live.

One way to reduce nitrogen emissions from farms would be to simply use fertilizer more efficiently. But—as we’ve seen with fossil fuels (and antibiotics and plastics)—when humans have a miraculous substance on our hands, we just can’t seem to use it at levels that minimize its impact. We instead seem compelled to throw around as much of the stuff as we can. But even if we were to start using less fertilizer now, we are past time to choose a single technique to curb greenhouse gas emissions; we need to put them all into action.

Denitrifying bacteria reduces levels of nitrous oxide in soil by converting it to the molecular form of nitrogen found in air. They use it as an oxidizer for respiration under conditions with low or no oxygen. So adding these nitrogen-respiring bacteria to soil could help decrease nitrous oxide emissions.

Modifying the microbiome of soil is just as hard as modifying the microbiome in our bodies. So instead of trying to promote the growth of any denitrifying bacteria that might happen to already be in soil, researchers decided to grow them externally and then add them in. Their source was partially treated sewage, called digestate, that was destined as organic fertilizer anyway. Keeping the digestate in oxygen-free conditions enriched their levels of one strain of nitrogen-respiring bacteria.

The researchers homed in on this particular strain because it has the enzyme needed to break down nitrous oxide, but not the enzymes used to make it from other nitrogen compounds. And although it is not the fastest, most efficient strain at nitrogen respiration, it won because it is the most tenacious: It grows to high concentrations even when oxygen is present, and it works well in soil.

When this digestate was mixed into soil, fertilizer-induced emissions were reduced by 50–95 percent, depending on the pH and organic carbon content of the soils. The effect lasted over the entire growing season. The presence of the added nitrogen-respiring bacteria did not seem to affect the indigenous microbiota already present in the soil, and the added bacteria did not carry genes for antibiotic resistance or pathogenicity, which is obviously essential if they are to be used in farming. What hasn’t been tested yet, however, is whether the presence of these bacteria influence the growth of crops.

Using mathematical modeling of future emissions, the researchers concluded that adding these bacteria to soil could reduce nitrous oxide emissions by 60 percent, and if they are added to all liquid manure systems in Europe, Europe could reduce its anthropogenic nitrous oxide emissions by 3 to 4 percent.

Nature, 2024.  DOI: 10.1038/s41586-024-07464-3

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Researchers make a plastic that includes bacteria that can digest it

bacteria, Biology, chemistry, evolution, materials science, plastics, Science / /

It’s alive! —

Bacterial spores strengthen the plastic, then revive to digest it in landfills.

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Image of two containers of dirt, one with a degraded piece of plastic in it.

Han Sol Kim

One reason plastic waste persists in the environment is because there’s not much that can eat it. The chemical structure of most polymers is stable and different enough from existing food sources that bacteria didn’t have enzymes that could digest them. Evolution has started to change that situation, though, and a number of strains have been identified that can digest some common plastics.

An international team of researchers has decided to take advantage of those strains and bundle plastic-eating bacteria into the plastic. To keep them from eating it while it’s in use, the bacteria is mixed in as inactive spores that should (mostly—more on this below) only start digesting the plastic once it’s released into the environment. To get this to work, the researchers had to evolve a bacterial strain that could tolerate the manufacturing process. It turns out that the evolved bacteria made the plastic even stronger.

Bacteria meet plastics

Plastics are formed of polymers, long chains of identical molecules linked together by chemical bonds. While they can be broken down chemically, the process is often energy-intensive and doesn’t leave useful chemicals behind. One alternative is to get bacteria to do it for us. If they’ve got an enzyme that breaks the chemical bonds of a polymer, they can often use the resulting small molecules as an energy source.

The problem has been that the chemical linkages in the polymers are often distinct from the chemicals that living things have come across in the past, so enzymes that break down polymers have been rare. But, with dozens of years of exposure to plastics, that’s starting to change, and a number of plastic-eating bacterial strains have been discovered recently.

This breakdown process still requires that the bacteria and plastics find each other in the environment, though. So a team of researchers decided to put the bacteria in the plastic itself.

The plastic they worked with is called thermoplastic polyurethane (TPU), something you can find everywhere from bicycle inner tubes to the coating on your ethernet cables. Conveniently, there are already bacteria that have been identified that can break down TPU, including a species called Bacillus subtilis, a harmless soil bacterium that has also colonized our digestive tracts. B. subtilis also has a feature that makes it very useful for this work: It forms spores.

This feature handles one of the biggest problems with incorporating bacteria into materials: The materials often don’t provide an environment where living things can thrive. Spores, on the other hand, are used by bacteria to wait out otherwise intolerable conditions, and then return to normal growth when things improve. The idea behind the new work is that B. subtilis spores remain in suspended animation while the TPU is in use and then re-activate and digest it once it’s disposed of.

In practical terms, this works because spores only reactivate once nutritional conditions are sufficiently promising. An Ethernet cable or the inside of a bike tire is unlikely to see conditions that will wake the bacteria. But if that same TPU ends up in a landfill or even the side of the road, nutrients in the soil could trigger the spores to get to work digesting it.

The researchers’ initial problem was that the manufacturing of TPU products usually involves extruding the plastic at high temperatures, which are normally used to kill bacteria. In this case, they found that a typical manufacturing temperature (130° C) killed over 90 percent of the B. subtilis spores in just one minute.

So, they started out by exposing B. subtilis spores to lower temperatures and short periods of heat that were enough to kill most of the bacteria. The survivors were grown up, made to sporulate, and then exposed to a slightly longer period of heat or even higher temperatures. Over time, B. subtilis evolved the ability to tolerate a half hour of temperatures that would kill most of the original strain. The resulting strain was then incorporated into TPU, which was then formed into plastics through a normal extrusion process.

You might expect that putting a bunch of biological material into a plastic would weaken it. But the opposite turned out to be true, as various measures of its tensile strength showed that the spore-containing plastic was stronger than pure plastic. It turns out that the spores have a water-repelling surface that interacts strongly with the polymer strands in the plastic. The heat-resistant strain of bacteria repelled water even more strongly, and plastics made with these spores was tougher still.

To simulate landfilling or litter with the plastic, the researchers placed them in compost. Even without any bacteria, there were organisms present that could degrade it; by five months in the compost, plain TPU lost nearly half its mass. But with B. subtilis spores incorporated, the plastic lost 93 percent of its mass over the same time period.

This doesn’t mean our plastics problem is solved. Obviously, TPU breaks down relatively easily. There are lots of plastics that don’t break down significantly, and may not be compatible with incorporating bacterial spores. In addition, it’s possible that some TPU uses would expose the plastic to environments that would activate the spores—something like food handling or buried cabling. Still, it’s possible this new breakdown process can provide a solution in some cases, making it worth exploring further.

Nature Communications, 2024. DOI: 10.1038/s41467-024-47132-8  (About DOIs).

Listing image by Han Sol Kim

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should-you-flush-with-toilet-lid-up-or-down?-study-says-it-doesn’t-matter

Should you flush with toilet lid up or down? Study says it doesn’t matter

bacteria, Biology, cross contamination, epidemiology, fluid dynamics, hygiene, sanitation, Science, toilet plumes, toilets, viral aerosols / /
Whether the toilet lid is up or down doesn't make much difference in the spread of airborne bacterial and viral particles.

Enlarge / Whether the toilet lid is up or down doesn’t make much difference in the spread of airborne bacterial and viral particles.

File this one under “Studies We Wish Had Let Us Remain Ignorant.” Scientists at the University of Arizona decided to investigate whether closing the toilet lid before flushing reduces cross-contamination of bathroom surfaces by airborne bacterial and viral particles via “toilet plumes.” The bad news is that putting a lid on it doesn’t result in any substantial reduction in contamination, according to their recent paper published in the American Journal of Infection Control. The good news: Adding a disinfectant to the toilet bowl before flushing and using disinfectant dispensers in the tank significantly reduce cross-contamination.

Regarding toilet plumes, we’re not just talking about large water droplets that splatter when a toilet is flushed. Even smaller droplets can form and be spread into the surrounding air, potentially carrying bacteria like E. coli or a virus (e.g., norovirus) if an infected person has previously used said toilet. Pathogens can linger in the bowl even after repeated flushes, just waiting for their chance to launch into the air and spread disease. That’s because larger droplets, in particular, can settle on surfaces before they dry, while smaller ones travel further on natural air currents.

The first experiments examining whether toilet plumes contained contaminated particles were done in the 1950s, and the notion that disease could be spread this way was popularized in a 1975 study. In 2022, physicists and engineers at the University of Colorado, Boulder, managed to visualize toilet plumes of tiny airborne particles ejected from toilets during a flush using a combination of green lasers and cameras. It made for some pretty vivid video footage:

Colorado researchers managed to visualize toilet plumes in 2022 using green lasers and strategically placed cameras.

“If it’s something you can’t see, it’s easy to represent it doesn’t exist,” study co-author John Grimaldi said at the time. They found that the ejected airborne particles could travel up to 6.6 feet per second, reaching heights of 4.9 feet above the toilet within 8 seconds. And if those particles were smaller (less than 5 microns), they could hang around in that air for over a minute.

More relevant to this latest paper, it’s been suggested that closing the lid before flushing could substantially reduce the airborne spread of contaminants. For example, in 2019, researchers at University College Cork deployed bioaerosol sensors in a shared lavatory for a week to monitor the number and size of contaminant particles. They concluded that flushing with the toilet lid down reduced airborne droplets between 30 and 60 percent. But this scenario also increased the diameter of the droplets and bacteria concentration. Leaving the lid down also means the airborne microdroplets are still detectable 16 minutes after flushing, 11 minutes longer than if one flushed with the lid up.

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Experimental antibiotic kills deadly superbug, opens whole new class of drugs

Acinetobacter baumannii, antibiotic, antibiotic resistance, bacteria, carbapenem-resistant Acinetobacter baumannii, CRAB, drug development, Gram-negative bacteria, health, LPS, roche, Science / /

fingers crossed —

The relatively large molecule clogs a transport system, leading to lethal toxicity.

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This Scanning Electron Microscope image depicts several clusters of aerobic Gram-negative, non-motile <i>Acinetobacter baumannii</i> bacteria under a magnification of 24,730x.” src=”https://cdn.arstechnica.net/wp-content/uploads/2024/01/10096-800×544.jpg”></img><figcaption> <p><a data-height=Enlarge / This Scanning Electron Microscope image depicts several clusters of aerobic Gram-negative, non-motile Acinetobacter baumannii bacteria under a magnification of 24,730x.

A new experimental antibiotic can handily knock off one of the world’s most notoriously drug-resistant and deadly bacteria —in lab dishes and mice, at least. It does so with a never-before-seen method, cracking open an entirely new class of drugs that could yield more desperately needed new therapies for fighting drug-resistant infections.

The findings appeared this week in a pair of papers published in Nature, which lay out the extensive drug development work conducted by researchers at Harvard University and the Swiss-based pharmaceutical company Roche.

In an accompanying commentary, chemists Morgan Gugger and Paul Hergenrother of the University of Illinois at Urbana-Champaign discussed the findings with optimism, noting that it has been more than 50 years since the Food and Drug Administration has approved a new class of antibiotics against the category of bacteria the drug targets: Gram-negative bacteria. This category—which includes gut pathogens such as E. coli, Salmonella, Shigella, and the bacteria that cause chlamydia, the bubonic plague, gonorrhea, whooping cough, cholera, and typhoid, to name a few—is extraordinarily challenging to kill because it’s defined by having a complex membrane structure that blocks most drugs, and it’s good at accumulating other drug-resistance strategies

Weighty finding

In this case, the new drug—dubbed zosurabalpin—fights off the Gram-negative bacterium carbapenem-resistant Acinetobacter baumannii, aka CRAB. Though it may sound obscure, it’s an opportunistic, invasive bacteria that often strikes hospitalized and critically ill patients, causing deadly infections worldwide. It is extensively drug-resistant, with ongoing emergence of pan-resistant strains around the world—in other words, strains that are resistant to every current antibiotic available. Mortality rates of invasive CRAB infections range from 40 to 60 percent. In 2017, the World Health Organization listed it as a priority 1: critical pathogen, for which new antibiotics are needed most urgently.

Zosurabalpin may just end up being that urgently needed drug, as Gugger and Hergenrother write in their commentary: “Given that zosurabalpin is already being tested in clinical trials, the future looks promising, with the possibility of a new antibiotic class being finally on the horizon for invasive CRAB infections.”

An international team of researchers, led by Michael Lobritz and Kenneth Bradley at Roche, first identified a precursor of zosurabalpin through an unusual screen. Most new antibiotics are small molecules—those that have molecular weights of less than 600 daltons. But in this case, researchers searched through a collection of 45,000 bigger, heavier compounds, called tethered macrocyclic peptides (MCPs), which have weights around 800 daltons. The molecules were screened against a collection of Gram-negative strains, including an A. baumannii strain. A group of compounds knocked back the bacteria, and the researchers selected the top one—with the handy handle of RO7036668. The molecule was then optimized and fine-tuned, including charge balancing, to make it more effective, soluble, and safe. This resulted in zosurabalpin.

Deadly drug

In further experiments, zosurabalpin proved effective at killing a collection of 129 clinical CRAB isolates, many of which were difficult-to-treat isolates. The experimental drug was also effective at ridding mice of infections with a pan-resistant A. baumannii isolate, meaning however the drug worked, it could circumvent existing resistance mechanisms.

Next, the researchers worked to figure out how zosurabalpin was killing off these pan-resistant, deadly bacteria. They did this using a standard method of subjecting the bacteria to varying concentrations of the antibiotic to induce spontaneous mutations. For bacteria that developed tolerance to zosurabalpin, the researchers used whole genome sequencing to identify where the mutations were. They found 43 distinct mutations, and most were in genes encoding LPS transport and biosynthesis machinery.

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