Genomes reveal five E. coli 'armor' types behind most multidrug-resistant bloodstream infections

                                                            Image designed by Tim Sandle

The first large-scale genetic study of E. coli's protective armour has identified the five capsule types that are responsible for 70% of all multidrug-resistant bloodstream infections in Europe. Researchers, including those at the Wellcome Sanger Institute, the University of Oslo, and their collaborators, analysed over 18,000 bacterial genomes from samples across all continents to investigate E. coli's armour and find new ways to penetrate it. 

Provided by Wellcome Trust Sanger Institute 

The study, published in Nature Microbiology, uncovered 90 different types of protective capsules, of which only 34% had been previously documented. The team also identified the capsule types that enable the bacterium to have the highest invasive potential, meaning it can transition from a harmless gut resident to a dangerous bloodstream invader.

By providing a blueprint of the armor that each E. coli strain has, this research can help in designing targeted vaccines and new treatments that can combat the most dangerous strains of E. coli while minimizing harm to beneficial strains of E. coli gut bacteria.

Science and microbiology gifts via Babbling Bacteria 

Escherichia coli (E. coli) is the leading cause of bloodstream infections worldwide. Most strains of E. coli are harmless and commonly found in the gut, however, if the bacterium gets into the bloodstream or the urinary tract, it can cause infections that range from mild to severe, particularly in people with a weakened immune system.

As an added challenge for health care providers, antibiotic resistance has become a frequent feature of such infections. Rates of antibiotic resistance in E. coli vary globally and, in the UK, over 40% of E. coli bloodstream infections are resistant to a key antibiotic.

Some bacteria, such as E. coli, have protective capsules that help shield the bacteria from the immune system and certain treatments, influencing the bacteria's ability to cause infections. Each bacterial strain has a different capsule makeup, and the capsules have markers, called antigens.

These antigens are often used as targets for new vaccines and treatments. However, for effective therapies to be developed, researchers need to know which capsule commonly causes the infection.

Traditional methods of mapping E. coli capsules are labor-intensive and uncommon. To address this, the team at the Sanger Institute and their collaborators genetically analyzed 18,000 E. coli samples. This allowed them to create the first digital database mapping capsule type and E. coli strain. They were then able to determine how common each type is using samples from nearly 8,000 people, ranging from newborns to those over 80 years old.

They found that capsule types are much more diverse than previously thought, mapping 90 different types, including 69 that had not been previously documented. The team also noted that different capsules were common in high-resource settings, such as the UK, compared to less industrialized regions such as Malawi and Pakistan.

For example, the researchers found that five specific capsule types (K1, K5, K52, K2, and K14) account for over 50% of all E. coli bloodstream infections and urinary tract infections across the UK, Norway, and France. Furthermore, a slightly different set (K1, K5, K52, K2, and K100) is responsible for 70% of multidrug-resistant E. coli infections in Europe.

While two of these (K1 and K5) do cause infections globally, there is more diversity in the strains that cause serious infections in low and middle-income countries than in Europe.

Due to these differences, the researchers highlight the importance of global data in future research, especially around drug and vaccine development, as the bacterial capsule types being targeted would vary depending on where the individual lived.

The team also found that E. coli has the ability to swap the genes that encode the capsule, sharing the information to build different types of armor between them.

Dr. Rebecca Gladstone, first and corresponding author at the University of Oslo, said, "By creating a digital library from over 18,000 bacterial genomes, we can see the true complexity of how E. coli protects itself, and how this armor is encoded in the genes. This research has expanded our scientific map from just a handful of known bacterial shields to a comprehensive database of 90 unique types, including nearly two-thirds that were previously unknown.

"Ultimately, this database provides the missing blueprint to identify strains most likely to cause serious infections, and design targeted vaccines and treatments to stop these."

Professor Jukka Corander, senior author at the Wellcome Sanger Institute and the University of Oslo, said, "This new research enables us to identify the strains of E. coli that are the biggest threats to human health. With this database, we can now see the bacterial capsule types that are prevalent in different countries, whether they cause serious infections, or if they are resistant to treatments.

"What our research also shows is the stark differences between capsule groups found in different regions, highlighting the need for systematic and standardized global data collection. Especially as we have found that E. coli can trade the genes for their protective shields between different genetic lineages.

"Understanding how these bacteria, especially the most drug-resistant ones, swap their coats, and having the global data to track this, is crucial for staying one step ahead of them in the fight against serious bloodstream infections."

Dr. Trevor Lawley, co-author at the Wellcome Sanger Institute, said, "Our microbiomes are made up of thousands of bacteria, and while the majority of these are beneficial, some strains can cause infections if they get into the bloodstream, such as E. coli.

"Large-scale population studies, such as the Baby Biome study, that provide a high-resolution view into the microbiome are essential for understanding the risk associated with certain bacterial strains, the genetic tools they use to cause infections, and how often they are found in the population.

"Understanding and tracking the E. coli strains that are most able to use their protective shield to move into the bloodstream and cause infection allows for the development of future targeted treatments while minimizing the harmful effects on the microbiome."

Publication details

Identification of transporter-dependent capsular K loci associated with invasive potential of Escherichia coli, Nature Microbiology (2026). DOI: 10.1038/s41564-026-02283-w

Journal information: Nature Microbiology 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

The billion-year reign of fungi that predated plants and made Earth livable

Image designed by Tim Sandle
 

Fungi may have shaped Earth’s landscapes long before plants appeared. By combining rare gene transfers with fossil evidence, researchers have traced fungal origins back nearly a billion years earlier than expected. These ancient fungi may have partnered with algae, recycling nutrients, breaking down rock, and creating primitive soils. Far from being silent background players, fungi were ecosystem engineers that prepared Earth’s surface for plants, fundamentally altering the course of life’s history. 

New research from Okinawa Institute of Science and Technology.

Complex multicellular life -- organisms made of many cooperating cells with specialized jobs -- evolved independently in five major groups: animals, land plants, fungi, red algae, and brown algae. On a planet once dominated by single-celled organisms, a revolutionary change occurred not once, but at least five separate times: the evolution of complex multicellular life. Understanding when these groups emerged is fundamental to piecing together the history of life on Earth."

Emergence here was not simply a matter of cells clumping together; it was the dawn of organisms, where cells took on specialized jobs and were organized into distinct tissues and organs, much like in our own bodies. This evolutionary leap required sophisticated new tools, including highly developed mechanisms for cells to adhere to one another and intricate systems for them to communicate across the organism, and arose independently in each of the five major groups.

The difficulties of dating evolutionary divergence

For most of these groups, the fossil record acts as a geological calendar, providing anchor points in deep time. For example, red algae show up possibly as early as about 1.6 billion years ago (in candidate seaweed-like fossils from India); animals appear by around 600 million years ago (Ediacaran fossils such as the quilted pancake like Dickinsonia); land plants take root roughly 470 million years ago (tiny fossil spores); and brown algae (kelp-like forms) diversified tens to hundreds of millions of years later still. Based on this evidence, a chronological picture of life's complexity emerges.

There is, however, a notable exception to this fossil-based timeline: fungi. The fungal kingdom has long been an enigma for paleontologists. Their typically soft, filamentous bodies mean they rarely fossilize well. Furthermore, unlike animals or plants, which appear to have a single origin of complex multicellularity, fungi evolved this trait multiple times from diverse unicellular ancestors, making it difficult to pinpoint a single origin event in the sparse fossil record.

Reading the genetic clock

To overcome the gaps in the fungal fossil record, scientists use a "molecular clock." The concept is that genetic mutations accumulate in an organism's DNA at a relatively steady rate over generations, like the ticking of a clock. By comparing the number of genetic differences between two species, researchers can estimate how long ago they diverged from a common ancestor.

However, a molecular clock is uncalibrated; it can reveal relative time but not absolute years. To set the clock, scientists need to calibrate it with "anchor points" from the fossil record. Given the scarcity of fungal fossils, this has always been a major challenge. The OIST-led team addressed this by incorporating a novel source of information: rare gene "swaps" between different fungal lineages, a process known as horizontal gene transfer (HGT).

While genes are normally passed down "vertically" from parent to child, HGT is like a gene jumping "sideways" from one species to another. These events provide powerful temporal clues," he says. "If a gene from lineage A is found to have jumped into lineage B, it establishes a clear rule: the ancestors of lineage A must be older than the descendants of lineage B.

By identifying 17 such transfers, the team established a series of "older than/younger than" relationships that, alongside fossil records, helped to tighten and constrain the fungal timeline.

A new history for an ancient kingdom

The analysis suggests a common ancestor of living fungi dating to roughly 1.4-0.9 billion years ago -- well before land plants. That timing supports a long prelude of fungi-algae interactions that helped set the stage for life on land.

Fungi run ecosystems -- recycling nutrients, partnering with other organisms, and sometimes causing disease. Pinning down their timeline shows fungi were diversifying long before plants, consistent with early partnerships with algae that likely helped pave the way for terrestrial ecosystems.

This revised timeline fundamentally reframes the story of life's colonization of land. It suggests that for hundreds of millions of years before the first true plants took root, fungi were already present, likely interacting with algae in microbial communities. This long, preparatory phase may have been essential for making Earth's continents habitable. By breaking down rock and cycling nutrients, these ancient fungi could have been the first true ecosystem engineers, creating the first primitive soils and fundamentally altering the terrestrial environment. In this new view, plants did not colonize a barren wasteland, but rather a world that had been prepared for them over eons by the ancient and persistent activity of the fungal kingdom.

The research paper reference is:

Lénárd L. Szánthó, Zsolt Merényi, Philip Donoghue, Toni Gabaldón, László G. Nagy, Gergely J. Szöllősi, Eduard Ocaña-Pallarès. A timetree of Fungi dated with fossils and horizontal gene transfers. Nature Ecology, 2025; DOI: 10.1038/s41559-025-02851-z 

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Understanding cleanroom changing room microorganisms

 

Changing rooms act as critical control points within pharmaceutical manufacturing facilities, functioning as microbial airlocks that limit personnel‑borne contamination entering classified processing areas. This study presents a five‑year comparative analysis (2022–2025) of microorganisms recovered from changing rooms and adjacent corridors, spanning cleanroom Grades D, C, and B. 

 

Environmental monitoring data—comprising surface contact plates, settle plates, and active air samples—were analysed and microbial profiles were evaluated. Across all areas, Gram‑positive cocci dominated, especially Micrococcus, Kocuria, and coagulase‑negative Staphylococcus, consistent with human skin flora. Grade D changing rooms showed the highest overall bioburden and organism diversity. 

 

Progressive reductions in microbial burden were observed as personnel transitioned through Grade C into Grade B areas. However, opportunities for improvement in gowning, cleaning, and moisture control were identified. This study provides a comprehensive dataset relating to pharmaceutical changing‑room microbiota and offers a reproducible framework for microbial profiling, trending, and benchmarking across cleanroom facilities.

To access, see:  https://www.ejpps.online/post/comparative-analysis-of-pharmaceutical-facility-changing-room-microbiota 

 

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Regulatory updates

 

The US Food and Drug Administration (FDA) has issued a draft guidance entitled ‘Computer Software Assurance for Production and Quality Management System Software’. Aimed at medical device manufacturers - check this out and other recent regulatory updates: https://www.rssl.com/insights/life-science-pharmaceuticals/issue-42-pharmaceutical-regulatory-roundup/ 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Pharmaceutical Resources

 See what Merck has to offer in terms of knowledge and resources, here.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Depyrogenation studies

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Obesity : The Microbiome at the Intersection of Nutrition and Pharma

With more than one billion people living with obesity worldwide—and its economic burden projected to reach $4.32 trillion annually by 2035—obesity remains one of the most pressing global health challenges of the 21st century. While GLP-1–based pharmacotherapies dominate headlines, Seventure Partners—a pioneering venture capital firm specializing in health, nutrition, and microbiome innovation through its dedicated Health for Life Capital funds—is releasing a scientific report that synthesizes global advances in gut microbiome research in obesity and metabolic health, highlighting its potential to serve as a foundation for sustainable, personalized therapeutic strategies that complement and extend conventional drug-based treatments.

A Global Health and Economic Crisis

According to the World Health Organization, 2.5 billion adults were overweight in 2022, including 890 million living with obesity. The World Obesity Atlas 2025 reports that this number has now surpassed one billion. If current trends continue, the WHO projects that 60% of adults will be affected by 2050. The World Obesity Federation estimates that the economic impact of overweight and obesity—including healthcare costs, lost productivity, and premature mortality—will reach $4.32 trillion annually by 2035, equivalent to nearly 3% of global GDP, comparable to the economic impact of COVID-19 in 2020.   In this context, GLP-1 (glucagon-like peptide-1) agonists have been hailed as a major breakthrough. The global market for these treatments is expected to reach $105 billion by 2030. However, this therapeutic class, as promising as it may be, also presents certain limitations that the scientific community is documenting with increasing precision.

The Limitations of Exclusively Drug based Approaches

		The Seventure Partners report highlights several unmet needs with current GLP-1 treatments. Clinical studies reveal that fewer than 50% of patients continue their treatment beyond 12 weeks, raising the critical question of result durability. Weight loss effects remain contingent on continuous medication use.   Furthermore, these therapies profoundly alter the intestinal ecosystem. GLP-1 agonists change how food transits through the gut and its fermentation patterns, which can disrupt microbiome composition. Other documented effects include loss of muscle mass (not just fat mass), frequent gastrointestinal disorders, and nutritional deficiencies linked to reduced appetite.

	"These findings do not call into question the proven benefits of GLP-1s, but they underscore the need for complementary and supplementary approaches to ensure healthy and sustainable weight loss over the long term," the report states.

	The Microbiome: An Underutilized Physiological Lever

	This is precisely where the gut microbiome offers major opportunities. GLP-1 is not just a pharmaceutical molecule—it is a hormone naturally produced by L-cells in the intestine. And this production is directly modulated by the microbiome.   Recent scientific research demonstrates that gut microbiome metabolites—particularly short-chain fatty acids (SCFAs)—naturally stimulate GLP-1 secretion. In other words, a healthy microbiome can activate the same metabolic pathways as medications, through physiological mechanisms.   The Seventure Partners report thus identifies the microbiome as a cornerstone of holistic, sustainable therapeutic strategies guided by precision medicine. This approach does not aim to replace existing treatments but to complement them and optimize their long-term effectiveness.

	A Rapidly Maturing Market

	This convergence of microbiome and metabolism is opening a high-growth market segment. According to analyses by ResearchAndMarkets and Global Industry Analysts, the global microbiome therapeutics market is expected to grow from $1.4 billion in 2024 to $21.5 billion by 2030, representing annual growth of nearly 57%. The obesity segment shows one of the strongest dynamics with a CAGR of 56.8%, alongside opportunities in oncology, chronic and age-related diseases, and gut-brain axis applications (neurodegenerative diseases, mental health, etc.).   For comparison, the GLP-1 agonist market is expected to reach $105 billion by 2030 (Morgan Stanley). The 1-to-5 ratio between these two markets illustrates both the maturity of pharmacological approaches and the significant catch-up potential of microbiome-based solutions.   Europe shows annual growth of 35.4% in this segment (Grand View Research), driven notably by public-private partnerships and the European Commission's 2025 Biotechnology Roadmap, which prioritizes microbial therapeutics for health and sustainability.

	A Broad Range of Therapeutic Innovations

	Isabelle de Cremoux's analysis maps the various product categories under development in this field: fecal microbiota transplantation (FMT), Microbiome Restoration Therapy (MRT), live biotherapeutic products (LBPs), next-generation probiotics, prebiotics, postbiotics, and functional dietary fibers. These innovations follow distinct regulatory pathways and offer complementary mechanisms of action.   A key finding emerges from the report: the need for personalized approaches. The variability in individual responses to microbiome-based treatments requires consideration of each patient's baseline microbiome composition and functions. This heralds the advent of precision medicine applied to obesity.

	Research Priorities to Be Strengthened

	The report also identifies priority research areas to accelerate the clinical translation of these approaches: filling remaining mechanistic gaps, prioritizing randomized clinical trials in humans over animal experimentation, and standardizing methodologies for microbiome data collection and analysis.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)