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/)

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/)

Ch-ch-ch-ch-changes: Bacteria, mutations & lab testing

 

Determining the presence of bacteria – either to know some cells are present or to target a specific number – requires growth and growth using a culture-based method is expressed by an increase in cells and/or biomass. The basis of many techniques is taking extremely low levels of various microbial types in a sample, and with the provision of suitable nutrients, atmosphere and temperature, enabling these cells to multiply up to levels that are high enough to count or identify.

To sustain microorganisms in the laboratory setting, subculturing is required. Uncontrolled subculturing can lead to temporary variations or to mutations occurring. This can affect the phenotypic properties or genetic nature of the cell.

How do these variations and mutations occur and why do they matter? Turn and face the strange...This week’s article considers culturing, culture media, subculturing, variations and mutations and what the implications are.

To read see: Mutations

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

Ref: https://www.linkedin.com/pulse/ch-ch-ch-ch-changes-bacteria-mutations-lab-testing-tim-z9bze/?published=t 

Diet matters less than evolutionary relationships in shaping gut microbiome

 

Gut microbes provide many services for their hosts, including digesting their food. Researchers have long known that mammals with specialized diets, such as carnivores and anteaters, have special types of gut microbes that allow them to eat that diet.

Is the same true in primates? In the largest published comparative dataset of non-human primate gut microbiomes to date, a new Northwestern University study set out to find whether leaf-eating primates have similar gut microbes that help them break down their leafy diet, which is full of fiber and toxins.

A common theme in the microbiome field is that host diet has large effects on the gut microbiome — both across lifespans (week-to-week changes in host diet change the gut microbiome) and across evolution (mammals with similar diets have similar gut microbes regardless of their evolutionary histories), said Katherine Amato, lead author of the study and assistant professor of anthropology in the Weinberg College of Arts and Sciences at Northwestern.

Therefore, they expected to see many similarities between leaf-eating primates, regardless of how closely related they were to each other. Rather, the researchers discovered that diet mattered much less than host evolutionary relationships in shaping the gut microbiome.

“Our data suggest that, across evolution, the effect of primate diet on the primate gut microbiome is not large,” Amato said. “Evolutionary relationships between primates are much more important for predicting microbiome composition and function.” 

The study is the first cross-species comparison of the gut microbiota that exclusively uses samples from wild animals.

“We conclude that although gut microbes play a critical role in supporting host dietary specializations, their impact is regulated through host physiology,” Amato said.

“Leaf-eating primates shared very few gut microbial characteristics. Instead, New World monkeys shared the most gut microbial characteristics with each other, regardless of diet. The same was true for Old World monkeys, lemurs and apes. These patterns appear to be the result of host physiological traits such as how the gastrointestinal tract is built.”

Cross-mammal examinations of the gut microbiome have been performed, Amato said, but they all had weaknesses in that species with similar diets also had similar evolutionary histories or physiology. Many studies also mixed captive and wild animals, and captivity is known to change the gut microbiome.

“This study was able to eliminate these issues due to the fact that leaf-eating evolved independently multiple times in the order Primates and is associated with a different physiology in each part of the primate tree,” Amato said. “We also only used wild primates, which compared to captive primates, are more likely to have gut microbiomes like those they evolved with.”

Further research could involve looking at more primate species with more varied diets and understanding how the human gut microbiome fits into this bigger evolutionary picture and what it can tell us about our physiology and health, Amato said.

“Evolutionary trends in host physiology outweigh dietary niche in structuring primate gut microbiomes” published online earlier this month in the ISME Journal: Multidisciplinary Journal of Microbial Ecology.

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

Bacillus spizizenii

 

The American Type Culture Collection (ATCC) #6633 bacterium Bacillus subtilis subsp. spizizenii (commonly Bacillus subtilis) has been reclassified as Bacillus spizizenii.

The change was the result of whole genome sequencing and the paper triggering the change was issued in 2020. However, several culture collections (and providers of cultures) were slow to adopt the taxonomic change.

Bacillus subtilis encompassed four subspecies: Bacillus subtilis subsp. subtilis, Bacillus subtilis subsp. inaquosorum, Bacillus subtilis subsp. spizizenii and Bacillus subtilis subsp. stercoris.

As a result of the research, each has become a separate species. Bacillus spizizenii is retained as the strain commonly used by the world’s culture collections for activities including growth promotion testing.

Reference:

Christopher A. Dunlap . Michael J. Bowman . Daniel R. Zeigler. Promotion of Bacillus subtilis subsp. inaquosorum, Bacillus subtilis subsp. spizizenii and Bacillus subtilis subsp. stercoris to species status. Antonie van Leeuwenhoek (2020) 113:1–12
 

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

Microbiology and Infectious Disease

Reviewed title: 'Dimer-monomer transition defines a novel hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome'

DOI link: https://doi.org/10.7554/eLife.98266.1

Summary: This study details a method to identify new antimicrobial drugs with therapeutic promise from bacterial datasets, providing clues for discovering alternatives to traditional antibiotics. eLife's editors describe it as a valuable new strategy for identifying novel lysins (a type of enzyme) with antimicrobial activity, and say that it provides solid evidence for the therapeutic potential of two such lysins discovered during the work.

Full eLife press release for further details: 'Harnessing big data helps scientists hone in on new antimicrobials' – https://elifesciences.org/for-the-press/a444a8f0/harnessing-big-data-helps-scientists-hone-in-on-new-antimicrobials

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

Endospores and mechanisms of resistance

 Image created by Tim Sandle

Endospores present a concern in controlled environments due to their resistance and indefinite survivability. The production of a spore is part of a sophisticated stress response. Here, the bacterial genome is copied and transferred into the safety of a spore (sporulation).

The spore remains dormant until environmental conditions improve. When conditions are favorable, the spore will germinate (generally rapidly) and become a functioning, vegetative cell.

This week’s article looks at what endospores are, how they are formed, and their relative resistance as part of improving our understanding of contamination control.

See:  https://www.linkedin.com/pulse/resistance-so-futile-endospores-mechanisms-tim-sfaxe/  

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

Evolution of Pseudomonas aeruginosa

 

Two hundred years ago, give or take the odd decade, Pseudomonas aeruginosa was an environmental bacterium (1), apparently not one, as far as medical records in the pre-microbiology days can be discerned, associated as a human pathogen (2).

Today, P. aeruginosa is associated with a high number of multidrug-resistant infections (3), many of which are nosocomial. Those especially vulnerable to the bacterium are people with underlying lung conditions.

It is estimated that P. aeruginosa is responsible for communicable diseases leading to over 500,000 deaths per year around the world, of which over 300,000 are associated with antimicrobial resistance (AMR). People who are immunocompromised as a result of conditions such as COPD (smoking-related lung damage), cystic fibrosis (CF), and non-CF bronchiectasis, are particularly susceptible.

This week’s article looks at the bacterium and also highlights some new research that charts how the organism evolved rapidly and then proceeded to spread globally over the last 200 years. At the heart of this are changes in human behavior. 

See: https://www.linkedin.com/pulse/200-year-old-problem-evolution-multi-drug-resistant-tim-lqn4e/  

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

Why hydrogen peroxide decontamination cycles can fail

Image designed by Tim Sandle.

When it works well, hydrogen peroxide in vapor or areolized form can be an effective means of ‘no-touch’ biodecontamination. However, operational limitations can create technical challenges for industrial‐scale adoption and inconsistency in the method of delivery can sometimes lead to fragility affecting the reproducibility of cycles.

This week’s article looks at hydrogen peroxide in the vapor or autolyzed form and considers what can result in cycle failures

See: Sandle on hydrogen peroxide decontamination

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

Introducing the Burkholderia cepacia complex

Image: CDC/Janice CarrContent Providers: Public Health Image Library (PHIL). Public Domain, https://commons.wikimedia.org/w/index.php?curid=2208169

Members of the Burkholderia cepacia complex (BCC), of which there are 18 different species, which are grouped into nine genomovars. These are aerobic organisms, widely distributed, and found in soil and water[i]. Importantly they can additionally survive for long periods in low-nutrient moist environments[ii], which make these organisms probable survivors within pharmaceutical grade water systems.

By Tim Sandle

B. cepacia is a human opportunistic pathogen and can cause pneumonia in immunocompromised individuals (when introduced into the air passages of a susceptible population); other risks to patients include endocarditis, wound infections, intravenous bacteremia, foot infection, respiratory infections. Some patient groups are at a greater risk than others, including elderly people, young children, cancer patients, pregnant women, and people with chronic illness[iii].

 

Bcc is of concern in relation to many pharmaceutical and healthcare facilities because many of the organisms within the group are resistant to organic solvents and antiseptics, and, to a degree, certain disinfectants[iv], with the resistance arising from several factors, including efflux pump mechanisms and resistance conferred through the organisms having a tendency to form biofilms under optimal conditions. Bcc organisms are also persistent, and they can readily survive in low nutrient conditions (such purified or distilled water).

 

It is important to understand the potential points or origin in pharmaceutical facilities (which is primarily low-nutrient environs like water, with the organisms adept at surviving under low nutrient conditions[v] [vi]; and which are reflective of the organisms often being able to adapt to different environmental conditions[vii]).

 

Organism characteristics

 

Burkholderia is a genus composed of over 60 organisms, many of which were formerly classed as Pseudomonas species. Within this are the Burkholderia cepacia complex, a group of some 17 organisms which are so closely related that they can, for the most part, only be differentiated by using a combination of multiple molecular diagnostic procedures.

 

Members of the Burkholderia cepacia complex are Gram-negative bacteria of the β-proteobacteria subdivision. This group is composed of plant, animal, and human pathogens. The organisms are widespread in both natural and ‘as built’ habitats[viii]. The organism after which the group is named was known as Pseudomonas cepacia prior to 1992. The bacterium was discovered by Walter H. Burkholder at Cornell Universityin1947.  Burkholder identified the bacterium as the source of onion skin rot (cepacia is Latin for “like onion”).

 

Burkholderia cepacia, along with other members, is an aerobic bacterium, elliptically shaped with a length of 5–15 μm. In term of biohazard, the organism has a biosafety level of 2.

 

Origins in pharmaceutical and healthcare

 

Bcc organisms are common to the environment and to water[ix].  With the manufacturing of drug products, the most common point of origin is with pharmaceutical water systems; a review by Sandle (2015) indicated that organisms fall into the top five category of recovered water-borne contaminants, as assessed over a fifteen year period[x]. This related to recoveries of water microbiota from purified water and Water-for-Injections systems. Issues arise foremost due to deficiencies in the design, operation and monitoring of water systems. A key risk relates to maintenance work like valve changes or where the system requires ‘cutting into’, such as to alter pipework[xi].

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[i] Lipuma J.J.. Update on the Burkholderia cepacia complex, Curr Opin Pulm Med. 2005; 11(6): 528-33

[ii] Lipuma, J.J, Currie B.J, Lum G.D, and Vandamme P. Burkholderia, Stenotrophomonas, Ralstonia, Cupriavidus, Pandoraea, Brevundimonas, Comamonas, Delftia, and Acidovorax In: Murray P.R, Baron E J, Jorgensen J.H, Landry ML, and Pfaller MA, editors. Manual of Clinical Microbiology. 9th Ed. Washington DC: ASM Press; 2007. p. 749-769.

[iii] Torbeck L, D. Raccasi, D.E. Guilfoyle, R.L. Friedman, D. Hussong. 2011. Burkholderia cepacia: This Decision is Overdue. PDA J. Pharm. Sci. Tech., 65(5): 535-43.

[iv] Hugo, WB et al. 1986. Factors Contributing to the Survival of a Strain of Pseudomonas cepacia In Chlorhexidine Solutions. Lett Appl Microbiol. 2:37-42

[v] W. Beckman and T.G. Lessie. Response of Pseudomonas cepacia to p-lactam antibiotics: utilization of penicillin G as the carbon source. J. Bacteriol. 1979; 140: 1126-1128

[vi] Martin, M et al 2011. Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths. J Hosp Infect 77:267-270

[vii] Vial, L., et al 2011. The various lifestyles of the Burkholderia cepacia complex species: a tribute to adaptation. Envir Microb 13(1):1-12

[viii] E. Mahenthiralingam, T.A. Urban, and J.B. Goldberg. The multifarious, multireplicon Burkholderia cepacia complex. Nature Reviews Microbiol. 2005; 3(2): 144–156

[ix] Springman, A.; Jacobs, J. L.; Somvanshi, V. S.; Sundin, G. W.; Mulks, M. H.; Whittam, T. S.; Viswanathan, P.; Gray, R. L.; Lipuma, J. J.; Ciche, T. A. Genetic diversity and multihost pathogenicity of clinical and environmental strains of Burkholderia cenocepacia. Appl. Environ. Microbiol. 2009, 75 (16), 5250–5260

[x] Sandle T (2015) Characterizing the Microbiota of a Pharmaceutical Water System-A Metadata Study. SOJ Microbiol Infect Page 5 of 8 Dis 3(2): 1-8

[xi] Ali, M. (2016) Burkholderia Cepacia in Pharmaceutical Industries, Int J Vaccines Vaccin 3(2): 00064. DOI: 10.15406/ijvv.2016.03.00064

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

Cleanroom microbiota: Why trending matters (video)

Cleanroom microbiota: Why trending matters. Tim Sandle takes a look at cleanroom microorganisms and considers the importance of profiling and trending contaminants: 

 

 

 

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

New species of marine bacteria that multiplies by a unique budding mechanism

 

The image shows Poriferisphaera hetertotrophicis, observed using Transmission Electron Microscopy (TEM). Image credit: Rikuan Zheng (CC BY 4.0)

Researchers have isolated a new strain of marine bacteria with unique characteristics from the ocean seabed. The bacterium multiplies by a unique budding mechanism and releases viruses to facilitate nitrogen metabolism.

The research advances scientific understanding of physiological mechanisms in deep-sea Planctomycetes bacteria, revealing unique characteristics such as being the only known species in the class of Phycisphaerae bacteria that uses a distinct budding model of division. 

Planctomycetes bacteria have blurred the lines between prokaryotes and eukaryotes. 

 

Planctomycetes bacteria possess several uncommon traits: a compartmentalized cell plan, an enlarged periplasm, a tightly folded nucleus-like structure, an endocytosis-like method of uptake, and a FtsZ-free method of cell division

The research provides convincing evidence that the new species is extensively involved in nitrogen assimilation and lives with a chronic virus (bacteriophage) that facilitates nitrogen metabolism. This bacteriophage – called phage-ZRK32 – was able to increase the growth of themarine bacterium dramatically by facilitating nitrogen metabolism.

Nitrogen cycling by bacteria is an essential process that frees up nitrogen for building into nucleic acids, amino acids and proteins – the building blocks of life.

The organism was isolated from sediment samples isolated from a deep-sea cold seep. The proposed name for the organism is Poriferisphaera hetertotrophicis.

The research appears in the journal eLife,titled "Physiological and metabolic insights into the first cultured anaerobic representative of deep-sea Planctomycetes bacteria".

[Image key: CM, outer membrane; Pi, cytoplasm; R, ribosome; N, nucleoid; ICM, cytoplasmic membrane; Py, periplasm; V, vesicle-like organelles]

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

Electrobiocorrosion: How bacteria cause iron to rust

Image source: https://en.wikipedia.org/w/index.php?curid=57097843

Microbial corrosion of iron is one of the mechanisms whereby structural damage occurs. The anaerobic microbial iron corrosion occurs due to conductive pili creating the process of electrobiocorrosion.

 

Iron not only rusts on contact with oxygen and water. Some bacteria can decompose iron anaerobically. The sediment-dwelling bacterium Geobacter sulfurreducens uses electrically conductive protein threads for this purpose. The bacteria produce magnetite from the iron, which promotes further corrosion in a positive feedback loop. 

 

 

G. sulfurreducens is a rod-shaped microbe with a Gram-negative cell wall. Geobacter is known as a type of bacteria that is able to conduct levels of electricity, and the species G. sulfurreducens is also known as “electricigens” due to their ability to create an electric current and produce electricity.

 

Geobacter does not use atmospheric oxygen for respiration; instead, it draws energy from the transfer of electrons from iron, forming magnetite in the process. However, the mechanism by which Geobacter corrodes iron metal has been uncertain – until now.

 

The mechanism of action of electrobiocorrosion has been pinpointed by researchers based at the Northeastern University in Shenyang, China. This has shown how electrically conductive pili, thin filaments which grow out of the bacteria, play an important role in this mechanism.

 

Geobacter forms "e-pili" from conductive proteins. These e-pili act like electric wires, conducting electricity.

 

The researchers left two strains of Geobacter to grow on a stainless-steel surface until biofilms formed. One of the two strains formed conductive e-pili, while the other still produced pili, but had been genetically modified so that the pili were formed from less conductive proteins.

 

The researchers next observed that the bacterial strain that grew e-pili fared significantly better on the steel plate. This bacterium grew more and made deeper pits in the metal, demonstrating how much metal it was consuming. The researchers also measured a corrosion current, a direct sign of the oxidation of iron.

 

 

It was concluded that the bacteria with the e-pili formed a sort of "electrical connection" to the metal. Bacteria located further away in the biofilm, not in direct contact with the metal, were also able to supply themselves with electrons using e-pili.

 

As magnetite is formed during the corrosion of iron, and this mineral also conducts electricity, the scientists also investigated its influence on microbial corrosion. It was noted that not only did adding magnetite to the biofilm increase the growth of Geobacter, it also led to a stronger corrosion current measured at the surface of the metal.

 

The research has significant corrosion implications and for attempts to improve corrosion protection.

 

See: Yuting Jin, Enze Zhou, Toshiyuki Ueki, et al.  Accelerated Microbial Corrosion by Magnetite and Electrically Conductive Pili through Direct Fe0‐to‐Microbe Electron Transfer. Angewandte Chemie International Edition, 2023; DOI: 10.1002/anie.202309005 

 

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