Treating anthrax beyond the 'point of no return'

Source: CDC - This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #2226

Anthrax, an infectious disease caused by the bacterium Bacillus anthracis, is often treatable in its early stages. But once the disease has progressed beyond the "point of no return" after just a few days, patients are most likely to die.

In a new study, University of Pittsburgh researchers show that a cocktail of growth factors reversed would-be lethal cell damage in mice with anthrax, suggesting that this approach could be adapted for use in patients beyond the brink.

When B. anthracis enters the body through inhalation, ingestion, injection or contact with skin, it produces two proteins that combine to form lethal toxin.

Early on, anthrax can be treated with antibiotics that eliminate the bacterium or antibodies that neutralize lethal toxin before it enters cells. But once inside cells, the toxin inactivates members of a group of enzymes known as MEKs by cleaving off one of their ends, disrupting the important pathways they control and rapidly causing widespread cellular, tissue and organ damage -- and death.

To learn more about the roles of MEK-controlled pathways in anthrax toxicity,the researchers generated mice with modified MEKs that were resistant to being cleaved by lethal toxin. These included MEK1 and MEK2, which control a pathway called ERK involved in cellular division and survival, and MEK3 and MEK6, which regulate the p38 pathway that's involved in stress-induced defense.

When exposed to lethal toxin or B. anthracis, mice with either modified MEK1/2 or MEK3/6 had much greater survival than normal animals, indicating that anthrax must inactivate both the ERK and p38 pathways to kill its host.

In mice and human cells exposed to lethal toxin or B. anthracis, a combination of three growth factors -- all individually approved as treatments for other conditions -- reactivated the ERK pathway and brought them back from the point of no return.

Because different types of cells in the body may require different growth factors to activate ERK, the researchers are now working to optimize a treatment for anthrax in humans.

See: 

Liu, J., Zuo, Z., Ewing, M. et al. ERK pathway reactivation prevents anthrax toxin lethality in mice. Nat Microbiol, 2025 DOI: 10.1038/s41564-025-01977-x

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

How do you explain the difference between a Quality Policy and a Quality Objective?

You're no stranger to the terms "Quality Policy" and "Quality Objectives," but how easy is it to convey their meaning - and their difference - to others in your organization?

By Lesley Worthington.
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The challenge lies in articulating these concepts so that they're as clear to the others as they are to you.
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Here are some ideas:

• Quality Policy: Think of explaining the Quality Policy as the organization’s promise about quality. It’s the big-picture statement that says, “Here’s what quality means to us, and here’s the direction we’re headed.” You could explain it to others by saying, “It’s like our quality compass—it keeps us pointed in the right direction and aligned with what the company stands for.” Bonus: Tie it back to the company’s mission or values so it feels even more relevant.
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• Quality Objectives: These are the stepping stones that help us fulfill the Quality Policy. They’re specific, measurable goals that show how we’re making progress toward that promise. To explain it simply, you could say, “Think of these as our quality scorecards—they help us track how well we’re delivering on our quality commitment. And just like business goals, they’ll shift and evolve to keep up with the company’s priorities.”

One quick tip for engaging upper management: Always try to tie these terms back to the business strategy. That's what they care about. And that might make them sit up and pay attention. Make it clear that a well-articulated Quality Policy and measurable Quality Objectives are not just quality goals but business imperatives.
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If an objective is too vague like "Improve customer satisfaction," help them refine it. Suggest a measurable alternative, such as "Increase customer retention rates by 10% this quarter." This gives everyone in the organization a concrete, trackable goal to aim for.
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The better we can articulate these key quality terms, the easier it will be to get buy-in from everyone - from the C-suite to those on the shop floor.

 

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

Why here? Why now? Protein-triggering bacteria spore formation characterized

A protein that enables bacteria to shut down into dormant spores under extreme conditions has been discovered. Sporulation is an effective survival mechanism, a state of dormancy, that some types of bacteria can enter into.

While many bacteria can tolerate harsh environments (like endolithic microorganisms, obtaining their energy and nutrients from rocks), the most extreme environments require sporulation to maintain survival. The process of sporulation enables bacteria to become very resistant to heat and radiation, creating life capsules for bacteria to survive in uninhabitable places including the most extreme places on the planet, such as under the permafrost, in the depths of the ocean or outer space (as some space missions have shown).

Discovering a new protein involved in sporulation in a group of bacteria could further our understanding of bacteria's ability to survive and potentially open up new avenues for antimicrobial therapies.

In this week’s article, the new research into the sporulating trigger protein is highlighted as well as an overview of some general aspects of bacterial sporulation. 

See: LinkedIn article

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

GMP Society

The GMP Society is an international organisation for Good Manufacturing Practices (GMPs) “Quality Professionals” to grow professionally and interact with like-minded individuals. We provide a forum for the free exchange of ideas and information to improve the production of pharmaceutical (medicinal) drug products.

Our member-led organisation affirms and promotes the principles of GMPs in all our professional activities by:

• Striving to protect the integrity of the pharmaceuticals we produce;
• Creating an environment where all products manufactured for human and veterinary use are of superior quality to confirm the well-being of the patient who uses our products;
• Providing training programs and certification programs to educate professionals with recognised, superior qualifications as we facilitate the development of GMP quality professionals in all markets, especially developing nations and regions;
• Fostering an environment of support to sustain not only our own companies, but all the companies manufacturing APIs and drug products for human and animal use;
• Working towards creating one international GMP standard for drug products and become recognised as a primary voice for GMP standard settings by regulatory authorities;
• Providing opportunities and benefits for our members in:
  • Information sharing and networking
  • Training
  • Education
  • Career development and
  • Personal advancement opportunities

Through our analysis and official documents, we will analyze international pharmaceutical regulations to provide compliance insight and focus for proper implementation, where appropriate. Communication among members is facilitated by active blogs, workshops, training programmes, conferences, GMP Review journal and our book publication program(s). 

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

Different Flow Hoods and How They Are Used in Experiments

                                                     Working in a laminar airflow cabinet. Image by Tim Sandle

What is a flow hood? It's a controlled environment created to minimize contamination, and it does this by directing filtered air over the designated workspace. Flow hoods are also known as clean benches or laminar flow hoods. Regardless of what name they go by, they're frequently used in laboratories to provide a sterile environmental setting for experiments by protecting researchers, equipment, and samples from airborne contaminants. Particle removal happens through ultra-low penetration air or high-efficiency particulate air filters before the air comes into the workspace. Flow hoods are available in several categories, and knowing their differences is crucial to picking the best hood for a particular application.

Different Flow Hoods and Their Uses in Experiments

You can find a variety of flow hoods for different applications. Knowing the primary categories helps you sift through your options.

Laminar Flow Hoods

A laminar flow hood makes a steady stream of filtered air. This stream moves continuously in a single direction to keep contamination from happening. Laminar flow hoods come in both horizontal and vertical configurations. Horizontal models direct clean air across a work surface and toward the user, and they're often used in pharmaceutical research, electronics assembly, and microbiology. Vertical models push filtered air down to the work surface to keep contaminants off of users; these are ideal for sample preparation and tissue culture work.

Biological Safety Cabinets

BSCs are intended to protect experiments, users, and the surrounding environment around them. HEPA filtration captures hazardous particles. Biohazard exposure is further prevented by airflow containment systems. BSCs are available in three different classes with varying levels of environmental protection. The highest levels of containment are totally enclosed and feature glove ports for handling dangerous pathogens.

Fume Hoods

Fume hoods aren't designed to be sterile, but they can prove important for any experiment that involves volatile chemicals. Users are protected when hazardous fumes get drawn away from a workspace and vented safely outside. Chemistry laboratories frequently employ these to minimize exposure to many different toxic substances.

PCR Workstations

Polymerase chain reaction workstations are a special category of laminar flow hoods. These are intended to minimize DNA contamination when amplification processes are underway. UV light is a common sterilization technology between experiments.

What To Watch Out for With Flow Hoods

There are several considerations to be mindful of with flow hoods. First, airflow disruptions can reduce effectiveness when objects are placed incorrectly in a flow hood. Secondly, ULPA and HEPA filters degrade with the passage of time; regular checks and replacements are essential to maintaining proper efficiency and function. Third, work practices need to be good habits in terms of avoiding rapid movements that might introduce contaminants or opening and closing flow hoods too frequently.

Proper hood selection is always important. Using the wrong kind of hood for your experiments might compromise the final results. For instance, don't use laminar flow hoods when working with hazardous materials. A biological safety cabinet is the more appropriate choice.

Protect Your Experiments

Flow hoods are important to experimental settings because they offer controlled environments with improved precision and safety. Choose the appropriate hood for your conditions and maintain it properly for reliable performance in laboratory settings and research applications.

Written by Taylor McKnight, Author for Cleatech LLC

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

Will ethanol be banned in Europe as the active ingredient for hand disinfectants?

Image by Tim Sandle

With ethanol be banned in the EU as the basis for hand disinfection? Do epidemiological studies confirm an increased risk for cancer from ethanol in exposed individuals? Why is the EU considering this move now?

I've noticed this report from Chemistry World:

Medical experts and health organisations from around the world have expressed concern over what they say would be a ‘misclassification’ of ethanol as a reprotoxic substance when it appears in biocidal products such as hand gels. They say there is no scientific evidence for the reclassification, which would result in significant risks to public health and safety if vital disinfectants were unavailable.

Disinfectant hand gels containing ethanol might no longer be available if the compound is reclassified as toxic to reproduction

The EU’s evaluation of ethanol’s use in products such as hand gels and disinfectants under the Biocidal Products Regulation (BPR) was assigned to Greek authorities back in 2007. In March, they submitted their draft report to the European Chemicals Agency (Echa) proposing that ethanol should be listed as a reprotoxic category 2 active substance (category 1 is the highest classification). This means it is a suspected human reproductive toxicant and follows some evidence of an adverse effect on sexual function and fertility, or on development. If ethanol was reclassified as a category 2, then biocides containing more than 3% would have to be labelled as reprotoxic. Effective hand-sanitising gels contain at least 60% alcohol.

Echa’s Biocidal Products Committee (BPC) is reviewing the report. Hanna-Kaisa Torkkeli, an Echa spokesperson, says it’s too early to predict the outcome, but expects an ‘opinion’ at the end of 2024 or, more likely, in 2025. The European Commission will make a final recommendation based on the BPC’s opinion.

To read the full article, see Chemistry World. 

In relation to this topic, this research paper, from 2024, concludes "There is no epidemiological evidence of toxicity for workers handling ethanol-containing products in industry or using EBHR in healthcare settings." EBHR = ethanol-based hand rubs.

Also see:  "Medical associations and expert committees urge that ethanol be approved as a virucidal active substance for use in hand antiseptics under the European Biocidal Products Regulation, without a CMR classification".

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

Microbiome new study: Human ancestral co-evolution

 Meta-organism entangled metabolic pathway of microbial 3M3SH malodor biotransformation steered by human precursor thiol conjugate substrate in ABCC11 haplotypes. Scientific Reports (Sci Rep) ISSN 2045-2322 (online)

A new microbiome study of interest.

The project concerns the evolutionary roots of human ancestral ethnic group global regionalizations, as involving skin niche microbial communities.

We address humans as “meta-organism” entities—i.e., entangled conglomerates of microbe genomes plus Homo sapiens genomes that have co-evolved through symbiotic mutualism.

The study asks the existential question: who is the evolutionary driver that steered modern humans into becoming such a meta-organism—was it people or microbes? How has survival advantage steered the ancient human origins of geographic regional clustering of ancestral ethnic groups with signature microbiomes?

Our data center on the key role of a microbe unique to humans, Staphylococcus hominis, and its engineering of “selfish gene” propagation opportunities by way of steering social interactions and communicable contacts among it’s human hosts whom are relegated as mere Trojan horse delivery vessels and incubators subserving their microbial companions. Within an extended family tree, this bacterial species is either inherited or not inherited by individuals, as governed by SNP variants of the human ABCC11 gene responsible for body odor vs. no odor binary pheromone communication.

The paper is:

Stevens, B.R., Roesch, L.F.W. Interplay of human ABCC11 transporter gene variants with axillary skin microbiome functional genomics. Nature Sci Rep 14, 28037 (2024).

Publisher’s link: https://doi.org/10.1038/s41598-024-78711-w .

You can jump to Fig. 6 for an overview lay summary.

A reprint PDF with additional Supplementary content is set out below:

Interplay of Human ABCC11 Transporter Gene Variants With Axillary Skin Microbiome Functional Genomic 2024 N... by Tim Sandle on Scribd

 

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