bacteria

Since the mass introduction of antibiotics last century, bacteria have been fighting back with an arsenal of defensive mechanisms. Some produce enzymes that can digest the antibiotic molecule before it takes effect. Others have developed cell membranes that can recognize antibiotics and close down the openings by which they would normally enter. Some can even eject the antibiotic molecule after taking it into the cell.

These defenses are growing faster than researchers can create new antibiotics to avoid these problems. "We are facing a war with bacteria," said Dr. Vanderlei Bagnato, a professor of biomedical engineering at Texas A&M University. "Antibiotic-resistant pneumonia is already killing 4 million people a year.

"If we don't do something about it now, people in the future are going to be dying of infections that today are easily treated with antibiotics. Then, we are not talking about 4 million people dying a year; we are possibly talking about hundreds of millions."

Bagnato intends to fight back. His weapon of choice in this war is light. This essentially drug-free strategy allows him to avoid one of the most dangerous parts of the escalating arms race with bacteria: antibiotics themselves.

"You have to understand that an antibiotic is a poison," Bagnato said. "It can kill your liver, your kidneys—it can kill everything in you. So, doctors want to use the absolute smallest amount. We call this the Minimum Inhibitory Concentration (MIC)."

The problem is that this MIC is constantly rising. As bacteria get better at avoiding the antibiotic molecules, doctors must administer increasing amounts of the drug to overwhelm the microbes' defenses. Eventually, the amount of antibiotic required to kill the bacteria hits levels where it would also kill the patient.

At this point, the disease has become functionally untreatable. Light-based therapies can change that.

"Light can go places where instruments will not," Bagnato said. "If I can find ways to make light penetrate you, I can reach cells and do things in there without cutting you or introducing a catheter. And I can use many different colors of light to activate and deactivate a wide variety of molecules."

For Bagnato's methods, light makes the second strike in a one-two punch. The first step of treatment is to administer a safe but photoreactive compound. The method varies depending on the location of the infection. For the treatment Bagnato already developed to combat antibacterial resistant throat infections in Brazil, patients merely need to hold a specially formulated lollipop in their mouths.

For a complex disease like antibacterial resistant pneumonia, patients will have to inhale a photoreactive substance carried in an aerosol.

When the infrared light that has passed harmlessly through the patient's body comes into contact with the photoreactive substance they previously inhaled, the result is an instantaneous chemical reaction—one that Bagnato has carefully planned using his decades of knowledge.

"I'm an atomic and molecular physicist. I use that knowledge of how light promotes reactions and how it interacts with atoms and molecules," Bagnato said. "I can destroy the bacteria's flux pump. I can open holes in the membrane. I can kill the mechanisms that the bacteria use to defend themselves."

With their defenses removed, the bacteria are vulnerable to a final coup de grace: the antibiotic that they had previously rendered useless.

"When those defenses are removed, safe levels of antibiotics can act again. What I've done with light has brought the MIC back down to the normal level," Bagnato said. "Immediately after I kill the defense mechanisms, I administer the antibiotic, and the antibiotic kills the bacteria."

The war against antibiotic resistant disease is only one of many that Bagnato is currently waging. His research runs the entire spectrum of pressing medical issues, from antibiotic-resistant diseases to cancer and diabetes—all problems that are only going to become more threatening in time. Over his career as a physicist turned biomedical engineer, Bagnato has founded more than 40 companies, become a member of the Vatican's Pontifical Academy of Sciences, and been inducted into the U.S. National Academy of Sciences and the National Academy of Engineering.

At age 67, he has no intention of giving up the fight.

"Each generation has to carry the next without asking for anything," Bagnato said. "It is scary. I'm afraid for my grandkids, who are going to face a different world. But I still get thrilled with each new discovery. People say that Murphy's Law means everything that can go wrong will go wrong, but that doesn't work for me. Go be wrong. I have crazy ideas, but I still go and try them. It doesn't always work in the way that I imagined, but it works somehow. Even the ones that had everything fail work in some way. So, Murphy is my friend."

Fifty years from now, millions of patients may owe their lives to Bagnato's work—with a little help from Murphy's Law.

(Source : MedicalExpress)

1) The skin barrier is weaker and drier.
Healthy skin is a tidy, water-holding barrier made of closely packed cells and oily lipids. In eczema that barrier is “leaky”: it loses moisture faster (higher transepidermal water loss), is physically drier, and the outer layer cracks or flakes more easily. Those cracks and gaps expose proteins and sugars deep in the skin that are normally hidden — and those exposed molecules act like handholds for bacteria.

2) S. aureus can stick and settle.
Staphylococcus aureus has surface proteins that recognize and bind to the exposed skin molecules. Once it latches on it’s much harder for the bacteria to be removed by normal rubbing or washing. In some cases the bacteria form biofilms — slimy communities that cling to the surface — which further helps them persist.

3) The skin’s chemical defenses are reduced.
Healthy skin makes natural antimicrobial peptides (AMPs) — small proteins (sometimes called the skin’s “antibiotics”) such as defensins and cathelicidins — that directly kill or slow bacteria. Eczema skin produces fewer of these AMPs, so there’s less biochemical resistance to bacterial growth. Put simply: there are fewer guards on duty.

4) Inflammation and scratching make things worse.
Eczema causes itching and inflammation. Scratching spreads bacteria across the skin surface and can create tiny breaks or wounds. Those micro-injuries are perfect entry points and new places for S. aureus to colonize and multiply. Inflammation itself changes the local environment (pH, nutrients, immune signals) in ways that can favor the bacteria.

5) The result: overgrowth, not a new “infection” from outside.
Because of the leaky barrier, fewer antimicrobial peptides, and ongoing inflammation and scratching, the skin becomes an environment where S. aureus can overgrow and dominate. That’s why people with eczema don’t usually “catch” S. aureus in the sense of a new external infection — rather, the bacteria that are commonly present on everyone’s skin or in the environment are able to expand on eczema-affected skin while healthy skin keeps their numbers low.

Short summary / analogy:
Think of healthy skin as a well-sealed house with locks and security lights (tight barrier + antimicrobial peptides). Eczema is like a house with broken windows and no lights: it’s easier for unwanted guests (S. aureus) to get inside, stay, and throw a noisy party.

A few important layers you could add, depending on how complete you want this to be. None of these contradict what you already wrote; they just deepen it.

1) Microbiome imbalance (not just one bacterium)
Healthy skin has a diverse microbiome where different microbes keep each other in check. In eczema, that diversity drops, and S. aureus crowds out other, more neutral or protective bacteria. Once it dominates, it actively makes the skin inflammation worse, which then further damages the barrier — a self-reinforcing loop.

2) Toxins and immune overstimulation
S. aureus doesn’t just sit there — it releases toxins and “superantigens” that overstimulate the immune system. These molecules can directly worsen redness, itching, and swelling, even without a classic infection. This helps explain why eczema flares often calm down when S. aureus levels are reduced, even if there was no obvious pus or infection.

3) Skin pH changes
Eczema skin often has a higher (less acidic) pH. Healthy, slightly acidic skin discourages S. aureus growth and supports antimicrobial peptides. When pH rises, AMPs work less well and S. aureus grows more easily — another subtle but important advantage for the bacteria.

4) Barrier proteins are altered
Many people with eczema have reduced or abnormal filaggrin and related barrier proteins. This weakens the structure of the outer skin layer and changes how skin cells mature, again exposing binding sites that S. aureus prefers.

5) The vicious cycle framing
It can help to explicitly state that this is a loop:

• Barrier damage → bacterial overgrowth

• Bacterial toxins → more inflammation and itching

• Scratching → more barrier damage

• Weaker defenses → even more bacterial dominance

Once that cycle is established, S. aureus isn’t just a passenger — it becomes an active driver of the disease.

6) Why this matters clinically
Adding one sentence on implications can strengthen the explanation:

This is why eczema treatment isn’t only about killing bacteria, but about restoring the skin barrier, reducing inflammation, and rebalancing the skin environment — otherwise S. aureus quickly returns.

(Source : ChatGPT)

Eczema (atopic dermatitis) is best understood today as a condition where three things meet and feed each other: an imperfect skin barrier, an over-reactive immune system, and changes in the microbes that live on the skin. The idea that bacteria play a meaningful role in eczema did not come all at once; it grew out of many observations over decades. The very bacteria most often implicated, staphylococci, were first described in pus by Alexander Ogston in the 1880s, which established that these microbes were common inhabitants and causes of skin infections long before eczema itself was studied in molecular detail. (CDC)

By the 1970s clinicians and microbiologists were noticing a striking pattern: inflamed eczema skin is frequently crowded with a single species, Staphylococcus aureus. In a widely cited paper from the mid-1970s, J. J. Leyden and colleagues showed that S. aureus was present at much higher numbers on eczema lesions than on healthy skin, and follow-up studies in the 1980s confirmed higher carriage and density of the bacterium on both lesional and apparently normal skin of people with atopic dermatitis. Those clinical microbiology findings shifted thinking from “eczema is only an immune or allergic disease” to a model in which microbes help drive flares. (PubMed)

Laboratory work over the next decades explained how the bacteria make things worse. Certain strains of S. aureus produce a mix of molecules — toxins, enzymes and so-called superantigens — that directly damage skin cells, break down the barrier, and powerfully stimulate immune cells. Some toxins punch holes in keratinocytes (the main skin cells), other proteins act like potent signals that make immune cells release inflammatory chemicals, and proteases can expose nerve endings that produce intense itch. Together, these bacterial products turn a vulnerable patch of skin into a site of escalating inflammation. Reviews and experimental studies over the 1990s–2020s summarized and confirmed these mechanisms. (PMC)

At the same time, genetic discoveries clarified why some people are more vulnerable in the first place. A landmark 2006 genetics paper led by Colin N. A. Palmer and collaborators showed that loss-of-function mutations in the gene for filaggrin — a protein that helps form and hydrate the outer layer of skin — are a major risk factor for developing atopic dermatitis. People with filaggrin defects have a weaker barrier, so irritants and microbes get in more easily; that helps explain why the bacterial overgrowth pattern is so common in eczema. The filaggrin discovery shifted research and treatment emphasis toward protecting and repairing the skin barrier, not only suppressing inflammation. (PubMed)

More recently, DNA sequencing and careful sampling have shown that S. aureus doesn’t just passively sit on eczematous skin: particular strains adapt to the inflamed environment, acquire mutations, and express genes that increase their capacity to stick, make toxins, and survive the local conditions. Genomic studies and microevolution analyses in the 2010s and 2020s have mapped those changes and made it clear that the interaction between host (skin + immune system) and bacteria is dynamic — the skin environment shapes the bacteria and the bacteria shape the immune response. (news.mit.edu)

All this history explains why modern treatments take a mixed approach. Restoring the barrier (moisturizers, emollients), calming the over-active immune response when needed (topical steroids or newer targeted drugs), and reducing the harmful activity of bacteria (short courses of antibiotics in some cases, antiseptic washes, or newer anti-virulence strategies) can all be useful — and they work best when combined thoughtfully. One recent innovation, developed by researchers at The University of Hong Kong, is a plant-based moisturizer called Anesinin that aims to “tame” S. aureus by suppressing the bacteria’s toxin production rather than killing the bacteria outright; this is an application of the anti-virulence idea that emerged from the biological studies described above. Early reports are promising but larger clinical trials and peer-reviewed data will be needed to know how broadly and durably such products help. (tech-transfer.med.hku.hk)

In short, eczema is not a simple autoimmune attack but a condition where a weak skin barrier, a sensitized immune system, and sometimes opportunistic bacteria together create a self-reinforcing loop of itch, inflammation and barrier breakdown. The historical arc — from Ogston’s 19th-century description of staphylococci through the 1970s clinical associations, the 2006 filaggrin genetics breakthrough, and the genomics and mechanistic studies of recent years — shows how the field moved from seeing eczema as purely “immune” to seeing it as an ecosystem problem in which bacteria can be important drivers.

(Source : ChatGPT)

In a study published in PNAS, scientists reveal that the survival of the bacterium responsible for tuberculosis, Mycobacterium tuberculosis, depends on a specialized transporter that enables it to absorb sulfate, a mineral form of sulfur. This transporter is highly specific to M. tuberculosis and could therefore be a target for drugs without side effects on human cells.

Tuberculosis, still a formidable enemy

Tuberculosis remains one of the deadliest infectious diseases today. Each year, it affects millions of people worldwide and continues to claim many lives, despite the existence of a vaccine and available treatments. In 2023, the World Health Organization reported 10.8 million new cases. The situation is further complicated by the emergence of antibiotic-resistant strains: these bacteria evade current treatments—which are already lengthy and difficult to follow—making the search for new solutions more urgent than ever.

Understanding the bacterium’s lifestyle to fight it more effectively

Tuberculosis is caused by a bacterium known as Mycobacterium tuberculosis. To combat it effectively, it is essential to understand its way of life. How does it survive inside the human body? How does it hijack our immune defenses to its own advantage? And above all, what mechanisms allow it to persist for years in a dormant state before reactivating to cause disease? These are the fundamental questions that a team of French scientists set out to address—leading to a major breakthrough published in the journal PNAS.
A discovery about the bacterium’s sulfur intake

For a long time, the scientific community believed that the bacterium fed mainly on organic sulfur, particularly from methionine, an amino acid taken directly from our cells. But this study overturns that view: the scientists show that M. tuberculosis actually prefers to import “inorganic” sulfate—a form of sulfur present in our bodies—through a specialized transporter named SubI-CysTWA.
To reach this conclusion, they used a highly precise imaging technology called NanoSIMS, which makes it possible to visualize chemical elements—including sulfur—directly within the cells infected by the bacterium. They observed that the bacterium stores large amounts of sulfur derived from sulfate, especially when it is in full activity.

The SubI transporter is required for sulfate import in intracellular bacteria.

The bacteria (M. tuberculosis) were cultured in the presence of glucose labeled with the isotope ¹³C to allow visualization within infected macrophages (left panels). The cells were incubated with sulfate labeled with ³³S in order to track the molecule inside infected cells (right panels). The cells were infected either with wild-type bacteria (top panels) or with a mutant lacking an active SubI transporter (bottom panels). The figure shows sulfate accumulation in the wild-type bacteria, but not in those that do not express the transporter.

A weak point to exploit for future treatments

The scientists then inactivated the gene responsible for producing this transporter. The result: the growth of the bacterium in laboratory cultures slowed down, and its survival decreased in the lungs of infected mice. It also became more sensitive to oxidative stress—a natural reaction of our defenses against pathogens.
This dependency is particularly interesting because the SubI-CysTWA transporter exists only in M. tuberculosis. Drugs targeting this mechanism could therefore weaken the bacterium without harming human cells. Such an approach could also boost the effectiveness of antibiotics already in use, such as isoniazid, and help shorten treatment duration.

A promising breakthrough

In a context where current treatments are lengthy and resistance is on the rise, this discovery opens a new avenue: blocking access to sulfate to prevent the bacterium from defending itself. In the long term, this could improve treatment efficacy, limit resistance, and ultimately save many lives.

(Source : Institute of Biology Paris-Seine)