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A new powerful antibiotic, isolated from bacteria that could not be studied before, seems capable to combat harmful bacteria and even multi-resistant 'superbugs'. Named Clovibactin, the antibiotic appears to kill bacteria in an unusual way, making it more difficult for bacteria to develop any resistance against it. Researchers from Utrecht University, Bonn University (Germany), the German Center for Infection Research (DZIF), Northeastern University of Boston (USA), and the company NovoBiotic Pharmaceuticals (Cambridge, USA) now share the discovery of Clovibactin and its killing mechanism in the scientific journal Cell.

Urgent need for new antibiotics

Antimicrobial resistance is a major problem for human health and researchers worldwide are looking for new solutions. "We urgently need new antibiotics to combat bacteria that become increasingly resistant to most clinically used antibiotics," says Dr. Markus Weingarth, a researcher from the Chemistry Department of Utrecht University.

However, the discovery of new antibiotics is a challenge: few new antibiotics have been introduced into the clinics over the last decades, and then they often resemble older, already known antibiotics.

"Clovibactin is different," says Weingarth. "Since Clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance."

Antibiotic from bacterial dark matter

Clovibactin was discovered by NovoBiotic Pharmaceuticals, a small US-based early-stage company, and microbiologist Prof. Kim Lewis from Northeastern University, Boston. Earlier, they developed a device that allows to grow 'bacterial dark matter', which are so-called unculturable bacteria. Intriguingly, 99% of all bacteria are 'unculturable' and could not be grown in laboratories previously, hence they could not be mined for novel antibiotics. Using the device, called iCHip, the US researchers discovered Clovibactin in a bacterium isolated from a sandy soil from North Carolina: E. terrae ssp. Carolina.

In the joint Cell publication, NovoBiotic Pharmaceuticals shows that Clovibactin successfully attacks a broad spectrum of bacterial pathogens. It was also successfully used to treated mice infected with the superbug Staphylococcus aureus.

A broad target spectrum

Clovibactin appears to have an unusual killing mechanism. It targets not just one, but three different precursor molecules that are all essential for the construction of the cell wall, an envelope-like structure that surrounds bacteria. This was discovered by the group of Prof. Tanja Schneider from the University of Bonn in Germany, one of the Cell paper's co-authors.

Schneider: "The multi-target attack mechanism of Clovibactin blocks bacterial cell wall synthesis simultaneously at different positions. This improves the drug's activity and substantially increases its robustness to resistance development."

A cage-like structure

How exactly Clovibactin blocks the synthesis of the bacterial cell wall was unraveled by the team of Dr. Markus Weingarth from Utrecht University. They used a special technique called solid-state nuclear magnetic resonance (NMR) that allows to study Clovibactin's mechanism under similar conditions as in bacteria.

"Clovibactin wraps around the pyrophosphate like a tightly sitting glove. Like a cage that encloses its target" says Weingarth. This is was gives Clovibactin its name, which is derived from Greek word "Klouvi," which means cage. The remarkable aspect of Clovibactin's mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it ignores that variable sugar-peptide part of the targets. "As Clovibactin only binds to the immutable, conserved part of its targets, bacteria will have a much harder time developing any resistance against it. In fact, we did not observe any resistance to Clovibactin in our studies."

Fibrils capture the targets

Clovibactin can do even more. Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.

"Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why Clovibactin selectively damages bacterial cells but is not toxic to human cells," says Weingarth. "Clovibactin hence has potential for the design of improved therapeutics that kill bacterial pathogens without resistance development.."

Some jobs suck because they’re just not what you want to be doing; others suck because the workplace culture itself is a mess. It can be hard to tell if your workplace is toxic or if you just really hate it for your own reasons, but there are ways to parse it out. What every workplace should have

Per the U.S. Surgeon General, for optimal worker mental health and well-being, a workplace must have these five essentials:

• Protection from harm, both physical and mental: This means workplaces provide support that focuses on mental health, give you enough time to rest, prioritize your safety on the job, and make the environment safe and welcoming for everyone.
• Connection and community: A workplace should create inclusive cultures that enable workers to form trusting relationships and collaborate with one another.
• Work-life harmony: Workplaces with work-life harmony give employees some autonomy over how work is completed, offer flexible and predictable schedules, and respect the boundary between on- and off-hours. They also provide paid leave.
• A feeling of mattering at work: Employees should feel like they matter at their job, not like they’re just disposable laborers. To do this, companies should offer a living wage, involve workers in decisions, and recognize good work.
• Opportunities for growth: Finally, employees will have better well-being if they’re given opportunities to grow in their careers, whether through training and education or mentoring. There should be clear, equitable pathways for advancement laid out and feedback given on work.

The Surgeon General came up with this framework after some grim statistics came from the pandemic: 76% of U.S. workers reported at least one mental health condition symptom in 2021, which was up 17% from two years prior, and 84% said they had encountered at least one factor in their workplace that had a negative impact on their mental health. How your job stacks up

The five essentials are a great framework from which you can inspect your own company. If it provides safety, connection, work-life harmony, a feeling that you matter, and opportunities for growth, it’s meeting the benchmarks of not being toxic—but if you still dislike it or feel it draining you, it might be time to switch jobs.

You don’t have to wait around for the right gig to fall in your lap. Research companies in your chosen field that meet those five requirements (Glassdoor and other employee review sites are great for this) and then send them a letter of interest. During any interviews, keep the five requirements top of mind and ask direct questions about how any potential new employer meets them. source

Having a big shade tree in your yard can provide a cooler hangout spot in the summer and cut back on the AC bill. But choosing and planting the right tree so it will grow to full height and provide the shade you want can be tricky. Some trees that are hardier and better suited for this than others, and there are some things you can do to help it have a healthy start.

Before you choose a tree, keep in mind that the best strong, tall, and shade-giving trees take awhile to grow. If you want a quicker solution, an awning or shade sale is a better option. Also, make sure to take root base into account when planting trees in the yard. Make sure the tree will have enough space to grow healthy roots that won’t damage your home’s foundation or walkways. Oak trees

Oak trees are one of the most frequently recommended trees in North America partly because there are so many native varieties to choose from. Depending on your region, you can almost always find an appropriate oak to plant, and they will grow slowly, but tend to be sturdy. An average oak will grow between a foot and a foot and a half a year, reaching maturity in about 60 years. Elm trees

Elm trees are also a popular choice for shade, and they grow more than twice as fast as oaks, at three to six feet per year. The American Elm can be found throughout the U.S. and parts of Canada in areas that are considered temperate, although because of a fungal infection called Dutch Elm Disease, there aren’t as many as there used to be. The roots of an elm tend to be a little bit shallower than other trees of their height but they can spread several feet past the size of the tree’s crown, making them unsuitable for smaller yards. Tulip Poplar trees

For the Eastern and Southeastern parts of the U.S., Tulip Poplars are a good choice for shade. It will grow between three and five feet per year and reach about 70 feet in height. In addition to their size, Tulip Poplars have tulip-shaped flowers that are brightly colored and flower from mid-May through June. Because of their substantial size, Tulip Poplars should be kept well clear of foundations. Maple trees

Maple trees are a good choice for most of North America, and there are plenty of varieties to choose from. Maples will grow about a foot to a foot and a half per year and reach varying heights depending on the species. Since maples come in a variety of sizes and types, they can be a good choice in many different yards, with dwarf maples being well-suited for smaller spaces. Make sure to get all of the information on whatever species of Maple you plant so you won’t be surprised by the size of the roots or crown. Hawthorn trees

Hawthorn trees can be grown in most parts of the U.S., and while they’re known as smaller trees, they can sometimes grow to be as tall as 30 feet, and grow one to two feet per year. Hawthorn trees have small flowers in early spring and produce berries in fall. They tend to be good habitats for small birds, as their thin branches aren’t strong enough for predators to land on. The berries also provide a food source for wildlife.

If you love your lawn, fine, but maybe hear me out: Lawns are the worst. Even if you don’t mind the watering, mowing, and chemicals, most lawns—including yours—are terrible. A non-comprehensive list of why lawns are awful

Grass, as a plant, is worthless. It’s a monoculture, meaning that there’s no diversity, and more susceptible to disease because they lack defenses from fellow plants. Biodiversity is why we plant nasturtiums next to vegetables—to protect the vegetables—and a lack of such diversity is why people often treat their lawn with chemicals.

Lawns also provide nothing to pollinators or animals, and often hurt surrounding wildlife with those same chemicals that are absorbed into the soil and plants nearby. Lawns rob soil of nutrients and are constantly in need of fertilizer. Chemicals and fertilizer often end up in the runoff, which pollutes our waterways and harms aquatic life. Lawns require a lot of water, time, effort, and money. Lawns simply suck. Be smart about killing your lawn

Don’t use chemicals to kill your lawn. If you want to benefit the soil, waterways, and nearby wildlife, using chemicals obviously defeats the purpose.

A lesser evil, but one you may also regret, is landscape fabric. Laying this black propylene is problematic for the soil and going to be a pain for you eventually. Once it’s stapled down, it’s almost impossible to get back up, and it also sheds, adding plastic to the soil, so any future plants will have to contend with both plastic and compacted, starved soil. Every gardener I know has had to extricate this nightmare from their yard eventually, and the irony is that it still doesn’t actually stop weeds. They grow through, practically giving you the finger. How to kill your lawn for free

You can rent a sod cutter, but they’re unwieldy and expensive. You can also turn over all your lawn with a shovel, but that’s a lot of work. Both of these methods are pretty fine, environmentally. But you can just sheet mulch your lawn, which is both easy and free.

Sheet mulching is the act of covering the ground with cardboard or something else that easily degrades. Cardboard is a nice, solid material that will block out the sun and oxygen from your lawn, and once starved of both, the grass will die—and better yet, it will compost in place. The cardboard will too, usually in a season or two, sticking around just long enough to kill the lawn. And as everything composts in place, it feeds the soil, creating microbes, mycorrhizae (the good fungus), and creating food for worms. It’ll also create pockets in the soil for other useful insects, and with the worms and insects will come birds and other small animals.

And cardboard is basically free. Use your Amazon boxes that you otherwise toss away, ask your neighbors for theirs, or ask your local grocery store. Remove the tape and staples, and use only uncoated cardboard (if it’s shiny, skip it). Lay it down, layering the ends, and make sure every spot is covered. Multiple layers is fine.

Reasonable people can agree a yard full of cardboard isn’t going to win the hearts and minds of your neighbors, so cover the cardboard with (also free) wood chips. Those chips will provide a uniform layer on your sheet mulch, help keep the cardboard in place, and hide the ugliness underneath. The chips will also compost over a few years, helping create a rich soil.

You can plant into your chips after a season. As you dig, you’ll see what’s left of the cardboard covered in white, which is mold and mycorrhizae—a sign of a healthy soil base. Those chips will break down in a year or two, and you can continue layering them on with new chips if you enjoy the look. They’re great to walk on and keep the ground nice and cool, in my opinion.

If you want to plant a ground cover or alternative lawn, you can. After a year, rake out the bigger chips still left, and you’ll be surprised to see how much has already broken down, leaving the smaller chips and compost behind. Layer on some more compost, and plant your ground cover right into it. There are also plenty of companies now like PT Lawn that specialize in alternative lawns of all kinds, from dog park mixes to pasture mixes. These diverse mixes look great, feed the soil and pollinators, and need less water and mowing.