Tag Archives: Chemicals

How inert, sleeping bacteria spring back to life

Solving a riddle that has confounded biologists since bacterial spores -; inert, sleeping bacteria -; were first described more than 150 years ago, researchers at Harvard Medical School have discovered a new kind of cellular sensor that allows spores to detect the presence of nutrients in their environment and quickly spring back to life.

It turns out that these sensors double as channels through the membrane and remain closed during dormancy but rapidly open when they detect nutrients. Once open, the channels allow electrically charged ions to flow out through the cell membrane, setting in motion the shedding of protective spore layers and the switching on of metabolic processes after years -; or even centuries -; of dormancy.

The team’s findings, published April 28 in Science, could help inform the design of ways to prevent dangerous bacterial spores from lying dormant for months, even years, before waking up again and causing outbreaks.

This discovery solves a puzzle that’s more than a century old. How do bacteria sense changes in their environment and take action to break out of dormancy when their systems are almost completely shut down inside a protective casing?”

David Rudner, study senior author, professor of microbiology, Blavatnik Institute at HMS

How sleeping bacteria come back to life

To survive adverse environmental conditions, some bacteria go into dormancy and become spores, with biological processes put on hold and layers of protective armor around the cell.

These biologically inert mini fortresses allow bacteria to wait out periods of famine and shield themselves from the ravages of extreme heat, dry spells, UV radiation, harsh chemicals, and antibiotics.

For more than a century, scientists have known that when the spores detect nutrients in their environment, they rapidly shed their protective layers and reignite their metabolic engines. Although the sensor that enables them to detect nutrients was discovered almost 50 years ago, the means of delivering the wake-up signal, and how that signal triggers bacterial revival remained a mystery.

In most cases, signaling relies on metabolic activity and often involves genes encoding proteins to make specific signaling molecules. However, these processes are all shut off inside a dormant bacterium, raising the question of how the signal induces the sleeping bacteria to wake up.

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In this study, Rudner and team discovered that the nutrient sensor itself assembles into a conduit that opens the cell back up for business. In response to nutrients, the conduit, a membrane channel, opens, allowing ions to escape from the spore interior. This initiates a cascade of reactions that allow the dormant cell to shed its protective armor and resume growth.

The scientists used multiple avenues to follow the twists and turns of the mystery. They deployed artificial intelligence tools to predict the structure of the intricately folded sensor complex, a structure made of five copies of the same sensor protein. They applied machine learning to identify interactions between subunits that make up the channel. They also used gene-editing techniques to induce bacteria to produce mutant sensors as a way to test how the computer-based predictions played out in living cells.

“The thing that I love about science is when you make a discovery and suddenly all these disparate observations that don’t make sense suddenly fall into place,” Rudner said. “It’s like you’re working on a puzzle, and you find where one piece goes and suddenly you can fit six more pieces very quickly.”

Rudner described the process of discovery in this case as a series of confounding observations that slowly took shape, thanks to a team of researchers with diverse perspectives working together synergistically.

Along the way, they kept making surprising observations that confused them, hints that suggested answers that didn’t seem like they could possibly be true.

Stitching the clues together

One early clue emerged when Yongqiang Gao, an HMS research fellow in the Rudner lab, was conducting a series of experiments with the microbe Bacillus subtilis, commonly found in soil and a cousin to the bacterium that causes anthrax. Gao introduced genes from other bacteria that form spores into B. subtilis to explore the idea that the mismatched proteins produced would interfere with germination. Much to his surprise, Gao found that in some cases the bacterial spores reawakened flawlessly with a set of proteins from a distantly related bacterium.

Lior Artzi, a postdoctoral fellow in the lab at the time of this research, came up with an explanation for Gao’s finding. What if the sensor was a kind of receptor that acts like a closed gate until it detects a signal, in this case a nutrient like a sugar or an amino acid? Once the sensor binds to the nutrient, the gate pops open, allowing ions to flow out of the spore.

In other words, the proteins from distantly related bacteria would not need to interact with mismatched B. subtilis spore proteins, but instead simply respond to changes in the electric state of the spore as ions begin to flow.

Rudner was initially skeptical of this hypothesis because the receptor didn’t fit the profile. It had almost none of the characteristics of an ion channel. But Artzi argued the sensor might be made up of multiple copies of the subunit working together in a more complex structure.

AI has entered the chat

Another postdoc, Jeremy Amon, an early adopter of AlphaFold, an AI tool that can predict the structure of proteins and protein complexes, was also studying spore germination and was primed to investigate the nutrient sensor.

The tool predicted that a particular receptor subunit assembles into a five-unit ring known as a pentamer. The predicted structure included a channel down the middle that could allow ions to pass through the spore’s membrane. The AI tool’s prediction was just what Artzi had suspected.

Gao, Artzi, and Amon then teamed up to test the AI-generated model. They worked closely with a third postdoc, Fernando Ramírez-Guadiana and the groups of Andrew Kruse, HMS professor of biological chemistry and molecular pharmacology, and computational biologist Deborah Marks, HMS associate professor of systems biology.

They engineered spores with altered receptor subunits predicted to widen the membrane channel and found the spores awoke in the absence of nutrient signals. On the flip side, they generated mutant subunits that they predicted would narrow the channel aperture. These spores failed to open the gate to release ions and awake from stasis in the presence of ample nutrients to coax them out of dormancy.

In other words, a slight deviation from the predicted configuration of the folded complex could leave the gate stuck open or shut, rendering it useless as a tool for waking up the dormant bacteria.

Implications for human health and food safety

Understanding how dormant bacteria spring back into life is not just an intellectually tantalizing puzzle, Rudner said, but one with important implications for human health. A number of bacteria that are capable of going into deep dormancy for stretches of time are dangerous, even deadly pathogens: The powdery white form of weaponized anthrax is a made up of bacterial spores.

Another dangerous spore-forming pathogen is Clostridioides difficile, which causes life-threatening diarrhea and colitis. Illness from C. difficile typically occurs after use of antibiotics that kill many intestinal bacteria but are useless against dormant spores. After treatment, C. difficile awakens from dormancy and can bloom, often with catastrophic consequences.

Eradicating spores is also a central challenge in food-processing plants because the dormant bacteria can resist sterilization due to their protective armor and dehydrated state. If sterilization is unsuccessful, germination and growth can cause serious foodborne illness and massive financial losses.

Understanding how spores sense nutrients and rapidly exit dormancy can enable researchers to develop ways to trigger germination early, making it possible to sterilize the bacteria, or block germination, keeping the bacteria trapped inside their protective shells, unable to grow, reproduce, and spoil food or cause disease.

Journal reference:

Gao, Y., et al. (2023) Bacterial spore germination receptors are nutrient-gated ion channels. Science. doi.org/10.1126/science.adg9829.

Smoking alters lung microbiome, leading to loss of diversity and community structure

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In a recent study published in the journal Access Microbiology, researchers explore the composition of the microbiome and interactions in the lower respiratory tract (LRT) in smokers. 

Study: Lower respiratory tract microbiome composition and community interactions in smokers. Image Credit: vchal / Shutterstock.com

The impact of smoking on the respiratory microbiome

Smoking has been shown to impact resident microbial communities present in different bodily regions. Previous studies have proposed various mechanisms responsible for this association, such as immunosuppression related to smoking, an increase in biofilm formation for specific species, and selection of species by the influence of local oxygen tension.

The upper airways and oral cavities may also directly interact with smoking chemicals, microbes, and heat from cigarettes, which can alter microbiome content. Recent studies have hypothesized that dysbiosis noted in the oral microbiome related to smoking may lead to a greater likelihood of experiencing complications in the respiratory tract among smokers. 

About the study

In the present study, researchers compare the LRT microbiome profiles of active smokers (AS), former smokers (FS), and non-smokers (NS) to describe the bacterial communities present in the lung.

The study involved volunteer subjects aged over 40 years of age who were either smokers of a minimum of 10 pack-years throughout their life or non-smokers. Former smokers qualified for the study if they had abstained from using tobacco for a minimum of 12 months, while AS smoked a minimum of one cigarette within three days of recruitment.

All study participants were required to complete a pulmonary function examination and thorough demographic and clinical questionnaire. The sampling process was standardized for all participants. The team extracted total deoxyribonucleic acid (DNA) from the bronchoalveolar lavages (BALs) specimens.

A single polymerase chain reaction (PCR) assessment was conducted to amplify the V6-V8 region present on the 16S ribosomal ribonucleic acid (rRNA) gene from the metagenomic DNA extracts of the BAL samples. Alpha diversity was estimated using Chao richness and inverse Simpson diversity indices. The DESeq2 algorithm was also used to detect differentiating taxa for each cohort.

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Study findings

All 46 smokers reported similar smoking exposure in terms of pack-years, including the FS quitting smoking on an average of about 10 years prior to enrollment. AS and FS exhibited reduced forced vital capacity (FVC), diffusing capacity for carbon monoxide (DL-CO), and forced expiratory volume at second 1 (FEV1); however, these variations were not remarkable according to the analysis of variance (ANOVA).

Over 3,600 reads with an average length of about 479 nucleotides were documented in each participant’s BAL, which facilitated the description of almost 400 operational taxonomic units (OTUs) per participant. The NS profile was sufficiently balanced between the prevalent phyla Bacteroides, Firmicutes, Proteobacteria, and Actinobacteria with comparatively slightly higher proportions. The FS cohort had a significant increase in Proteobacteria with reduced Bacteroides and Firmicutes levels. This pattern was also true for AS, with Proteobacteria increasing to 75% and Firmicutes declining to 11%.

Genus-level assessments indicated that most of the enhancement in Proteobacteria in AS and FS in comparison to its high proportion in NS was due to the genus Ralstonia, which increased from 2% in the NS, 28% in AS, and 21% in FS.

From the Firmicutes phylum, the Streptococcus and Veillonella genera, as well as Prevotella from the Bacteroidetes phyla exhibited the greatest decline in comparative abundance. Furthermore, the Propionibacterium genus of the Actinobacteria phylum exhibited a slight improvement from 3% in AS and FS to 0.8% in NS.

With respect to the NS profile, a greater number of upper-quartile taxa were distinguished from AS, whereas lower-quartile taxa were distinguished from FS.

NS exhibited a considerably higher mean diversity as compared to AS and FS. The mean diversity further increased when the participants were placed by declining richness, thus indicating that NS reported higher richness. Yet, the diversity evaluated with the inverse Simpson index had only an intermediate association with richness estimates and the participant’s smoking status.


The current study provides new insights into the complicated microbial communities found in the LRT and how this microbiome can be changed under different smoking conditions. The researchers also observed that the oral microbiota can settle in the lungs of smokers, which makes the study of the upper airway microbiome interesting for future research.

The microbiomes of former smokers appear to exhibit similar properties to those of both AS and NS. In the future, integration of the present findings with next-generation analytical techniques would help establish the effect of such microbial communities on human health.

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Journal reference:
  • Campos, M., Cickovski, T., Fernandez, M., et al. (2023). Lower respiratory tract microbiome composition and community interactions in smokers. Access Microbiology. doi:10.1099/acmi.0.000497.v3

Simple blood tests for telomeric protein could provide a valuable screen for certain cancers

Once thought incapable of encoding proteins due to their simple monotonous repetitions of DNA, tiny telomeres at the tips of our chromosomes seem to hold a potent biological function that’s potentially relevant to our understanding of cancer and aging.

Reporting in the Proceedings of the National Academy of Science, UNC School of Medicine researchers Taghreed Al-Turki, PhD, and Jack Griffith, PhD, made the stunning discovery that telomeres contain genetic information to produce two small proteins, one of which they found is elevated in some human cancer cells, as well as cells from patients suffering from telomere-related defects.

Based on our research, we think simple blood tests for these proteins could provide a valuable screen for certain cancers and other human diseases. These tests also could provide a measure of ‘telomere health,’ because we know telomeres shorten with age.”

Jack Griffith, PhD, the Kenan Distinguished Professor of Microbiology and Immunology and Member of the UNC Lineberger Comprehensive Cancer Center

Telomeres contain a unique DNA sequence consisting of endless repeats of TTAGGG bases that somehow inhibit chromosomes from sticking to each other. Two decades ago, the Griffith laboratory showed that the end of a telomere’s DNA loops back on itself to form a tiny circle, thus hiding the end and blocking chromosome-to-chromosome fusions. When cells divide, telomeres shorten, eventually becoming so short that the cell can no longer divide properly, leading to cell death.

Scientist first identified telomeres about 80 years ago, and because of their monotonous sequence, the established dogma in the field held that telomeres could not encode for any proteins, let alone ones with potent biological function.

In 2011 a group in Florida working on an inherited form of ALS reported that the culprit was an RNA molecule containing a six-base repeat which by a novel mechanism could generate a series of toxic proteins consisting of two amino acids repeating one after the other. Al-Turki and Griffith note in their paper a striking similarity of this RNA to the RNA generated from human telomeres, and they hypothesized that the same novel mechanism might be in play.

They conducted experiments – as described in the PNAS paper – to show how telomeric DNA can instruct the cell to produce signaling proteins they termed VR (valine-arginine) and GL (glycine-leucine). Signaling proteins are essentially chemicals that trigger a chain reaction of other proteins inside cells that then lead to a biological function important for health or disease.

Al-Turki and Griffith then chemically synthesized VR and GL to examine their properties using powerful electron and confocal microscopes along with state-of-the-art biological methods, revealing that the VR protein is present in elevated amounts in some human cancer cells, as well as cells from patients suffering from diseases resulting from defective telomeres.

“We think it’s possible that as we age, the amount of VR and GL in our blood will steadily rise, potentially providing a new biomarker for biological age as contrasted to chronological age,” said Al-Turki, a postdoctoral researcher in the Griffith lab. “We think inflammation may also trigger the production of these proteins.”

Griffith noted, “When you go against current thinking, you are usually wrong because you are bucking many people who’ve worked so diligently in their fields. But occasionally scientists have failed to put observations from two very distant fields together and that’s what we did. Discovering that telomeres encode two novel signaling proteins will change our understanding of cancer, aging, and how cells communicate with other cells.

“Many questions remain to be answered, but our biggest priority now is developing a simple blood test for these proteins. This could inform us of our biological age and also provide warnings of issues, such as cancer or inflammation.”

Journal reference:

Al-Turki, T., et al. (2023) Mammalian Telomeric RNA (TERRA) can be translated to produce valine-arginine and glycine-leucine dipeptide repeat proteins. PNAS. doi.org/10.1073/pnas.2221529120.

Chemicals accumulated in the vagina may contribute to spontaneous preterm birth

Chemicals that accumulate in the vagina, potentially originating from personal care products, may contribute to spontaneous preterm birth, according to a new study by researchers at Columbia University Vagelos College of Physicians and Surgeons.

The study of 232 pregnant women found that a handful of non-biological chemicals previously found in cosmetics and hygiene products are strongly associated with preterm birth.

Our findings suggest that we need to look more closely at whether common environmental exposures are in fact causing preterm births and, if so, where these exposures are coming from. The good news is that if these chemicals are to blame, it may be possible to limit these potentially harmful exposures.”

Tal Korem, PhD, study co-leader, assistant professor in the Program for Mathematical Genomics and the Departments of Systems Biology and Obstetrics and Gynecology at Columbia University

The study was published January 12 in Nature Microbiology.

Preterm birth, childbirth before 37 weeks of pregnancy, is the number one cause of neonatal death and can lead to a variety of lifelong health issues. Two-thirds of preterm births occur spontaneously, but despite extensive research, there are no methods for predicting or preventing spontaneous preterm birth.

Several studies have suggested that imbalances in the vaginal microbiome play a role in preterm birth and other problems during pregnancy. However, researchers have not been able to reproducibly link specific populations of microorganisms with adverse pregnancy outcomes.

The research team, co-led by Korem and Maayan Levy, PhD, of the University of Pennsylvania, decided to take a more expansive view of the vaginal microenvironment by looking at its metabolome. The metabolome is the complete set of small molecules found in a particular biological niche, including metabolites produced by local cells and microorganisms and molecules that come from external sources. “The metabolome can be seen as a functional readout of the ecosystem as a whole,” Korem says. “Microbiome profiling can tell us who the microbes are; metabolomics gets us close to understanding what the microbes are doing.”

In the current study, the researchers measured over 700 different metabolites in the second-trimester metabolome of 232 pregnant women, including 80 pregnancies that ended prematurely.

The study found multiple metabolites that were significantly higher in women who had delivered early than in those who delivered at full term.

“Several of these metabolites are chemicals that are not produced by humans or microbes-;what we call xenobiotics,” says Korem. “These include diethanolamine, ethyl-beta glucoside, tartrate, and ethylenediaminetetraacetic acid. While we did not identify the source of these xenobiotics in our participants, all could be found in cosmetics and hygiene products.”

Algorithm predicts preterm birth

Using machine learning models, the team also developed an algorithm based on metabolite levels that can predict preterm birth with good accuracy, potentially paving the way for early diagnostics.

Though the predictions were more accurate than models based on microbiome data and maternal characteristics (such as age, BMI, race, preterm birth history, and prior births), the new model still needs improvement and further validation before it could be used in the clinic.

Despite the current limitations, Korem says, “our results demonstrate that vaginal metabolites have the potential to predict, months in advance, which women are likely to deliver early.”

Journal reference:

Kindschuh, W.F., et al. (2023) Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome. Nature Microbiology. doi.org/10.1038/s41564-022-01293-8.

Study reveals subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma

Researchers from the Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered a novel subtype of Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) and EBV-associated immunosuppression in the tumor microenvironment (TME). These findings have provided novel insights into the traditional NPC pathogenesis model and highlights EBV-specific communications in the TME as potential therapeutic target in NPC. The research has been published in eBioMedicine.

Background and research findings

NPC has a high incidence rate in Southeast Asia, in particular Guangdong and Hong Kong. Due to its worldwide rarity, studies on NPC heavily rely on local research teams, and its pathogenesis mechanism remains largely unclear. In Hong Kong, NPC is the commonest cancer type for the men aged 20-44 and ranked 8th highest incidence rate among males. Strikingly, EBV is detected in 95% of the Hong Kong cases. Having thorough understanding of NPC pathogenesis, in particular the role of EBV, is critical for advancing the clinical diagnosis and treatment for this deadly disease and is an active research topic in the field.

The research team used a cutting-edge bioinformatics approach to comprehensively decode the epigenetics of the tumors dissected from NPC patients. EBV+NPC was believed to be massively dysregulated by the global DNA hypermethylation, a phenomenon that denotes a large-scale increase of methyl groups onto the DNA sequences within the cancer cells. These methyl-groups function like an ‘off-switch’ to inactivate tumor-suppressors that safeguard the cells from turning into a tumor, and thereby, promoting tumor development. Moreover, global DNA hypermethylation is rarely observed in non-EBV cancer types proposed to be associated with EBV and is a critical step in NPC pathogenesis.

The research team discovered that, in contrast to what was commonly believed, 20% of NPC cases were characterized by global DNA hypomethylation, which refers to a large-scale decrease of methyl groups onto the DNA sequences in the cancer cells. The study also discovered that EBV may reprogram the cell-cell communications[4]between the cancer cells and the immune cells, and consequently protect the cancer cells from being destroyed by the immune system.

Significance of the study

‘Commonly infected by EBV, the NPC tumours carried distinctive methylation patterns. This finding is not well-recognised by the NPC development model. When global DNA hypomethylation occurs during NPC pathogenesis, whether it occurs as an alternative pathway in a subset of patients and its potential of predicting patients’ survival, clinical features, and response to therapies are critical for understanding NPC and providing personalized treatments for patients.’ commented Dr Dai Wei, Assistant Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed.

Professor Maria Li Lung, Emeritus Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed, added, ‘Since the immunosuppressive cell-cell communications were associated with EBV, these communications are highly-specific to the tumours and could be potential therapeutic targets and biomarkers in NPC.’ ‘We are now designing experiments to explore this feasibility and understand the clinical impacts of NPC subtypes. We hope the work can be beneficial to NPC patients in Hong Kong.’

About the research team

This research was co-supervised by Dr Dai Wei, Assistant Professor, and Professor Maria Li Lung, Emeritus Professor of the Department of Clinical Oncology, School of Clinical Medicine, HKUMed. Dr Larry Chow Ka-yue and Mr Dittman Chung Lai-shun from the Department of Clinical Oncology, School of Clinical Medicine, HKUMed, are the co-first authors, Dr Tao Lihua, Scientific Officer, provided support to the research.

The collaborators included Dr Chan Kui-fat and Dr Stewart Tung Yuk from Department of Clinical Oncology and Department of Clinical Pathology from the Tuen Mun Hospital, Hong Kong; Professor Roger Ngan Kai-cheong, Professor Ng Wai-tong, Professor Anne Lee Wing-mui, Professor Dora Kwong Lai-wan, Dr Victor Lee Ho-fun and Dr Lam Ka-on from the Department of the Clinical Oncology, School of Clinical Medicine, HKUMed; Dr Yau Chun-chung from Department of Oncology from Princess Margaret Hospital, Hong Kong; Professor Chen Honglin and Dr Liu Jiayan from Department of Microbiology, School of Biomedical Sciences, HKUMed.

Journal reference:

Chow, L. K-Y., et al. (2022) Epigenomic landscape study reveals molecular subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma. eBioMedicine. doi.org/10.1016/j.ebiom.2022.104357.

Study confirms the growing resistance in non-pathogenic Listeria species

In the food processing industry, the deadly bacteria Listeria monocytogenes is monitored closely. Not only can the bacteria make people extremely ill, it is known to be developing resistance to various food safety measures across the world.

However, two ‘harmless’ species of Listeria are also developing a surprising number of characteristics potentially harmful to humans.

A Whole Genome Sequencing study in South Africa, from a team of researchers with first author Dr Thendo Mafuna at the University of Johannesburg, shows some of the changing characteristics of Listeria found in the country.

The study shows that Listeria innocua strains are developing resistance to temperature, pH, dehydration and other stresses; as well as hypervirulence genetically identical to that of Listeria monocytogenes.

Some strains of L. innocua and L. welshimeri in the study show all three genes for resistance to a widely-used disinfectant, from the quaternary ammonium compound (QAC or QUAT) group of chemicals.

Two strains of L. innocua they analyzed have developed three or more concerning pathogenic characteristics, including CRISPR CAS-type adaptive immune systems.

The two non-pathogenic strains of Listeria were sampled in raw, dried and processed meats at commercial food processing facilities in the country.

The study confirms other research showing growing resistance in non-pathogenic Listeria species in other parts of the world.

Shared genes with pathogenic species

The Listeria innocua that we tested has some of the genes that are also found in pathogenic Listeria monocytogenes.

Dr Thendo Mafuna, First Author, University of Johannesburg

Mafuna is from the Department of Biochemistry at the University of Johannesburg.

These shared genes between L. innocua and L. monocytogenes are also responsible for disease in humans; and stress tolerance such as resistance to the disinfectant Benzalkonium chloride (BC or BAC).

Research from others has shown that though Listeriosis is rarely caused by L. innocua, it does happen more often in people with compromised immune systems, he adds.

Benzalkonium chloride (BAC) is a member of a group of chemicals called Quaternary ammonium compounds, or QUATs. Quats are found in many common disinfectant products. They have been shown to be highly effective at killing bacteria, fungi and viruses.

All the L. innocua strains they tested also had the complete LIPI-4 hypervirulence gene sequence, which can cause disease in humans, he says. The LIPI-4 sequence they found in L. innocua is identical to that found in pathogenic L. monocytogenes, as recorded by the Pasteur Institute in Paris, France.

From raw, dried and processed meats

The samples and isolates analyzed in this study were collected between 2014 and 2019 by the South African Government’s Department of Agriculture, Land Reform and Rural Development (DALRRD). These were submitted to the Agricultural Research Council (ARC) at Onderstepoort Veterinary Research SA for analysis.

In total, 258 isolates from butcheries, abbatoirs, retail outlets, cold stores and processing facilities all over the country were studied. Of these, 38 were found to be nonpathogenic L. Innocua; and another three isolates found to be nonpathogenic L. welshimeri.

The isolates came from raw whole, raw processed, dried, and processed cooked, beef, chicken and pork meats. Dr. Itumeleng Matle at the Bacteriology Division, ARC in Onderstepoort did the microbiological analysis of Listeria isolation and identification.

The Whole Genome Sequencing (WGS) was done by Dr. Rian E. Pierneef at the ARC’s Biotechnology Platform at Onderstepoort.

Mafuna then compared the genome sequences with those recorded by the Pasteur Institute, in Paris, France; and performed the analysis for the study.

On the lookout

“We need to look at our own facilities in South Africa to really see what is happening. Our analyses of these bacteria can help us predict which sequence types to be on the look out for,” says Mafuna.

It is the number of harmful characteristics that the L. innocua strains share with L. monocytogenes that is concerning, he adds.

Food processors need to look out for Listeria innocua because it is becoming resistant to disinfectants that are used in industry to get rid of them. It would also be helpful to try different types of disinfectants to surfaces, he says. Switching from one type to another may prevent or delay the bacteria developing resistance to one type of disinfectant.

“Big industrial food processors may want to investigate how efficient BC or quat disinfectants are in their facilities. This can be done by taking swabs before cleaning and again after cleaning, culturing those, to see how well the disinfectant regimes are working,” says Mafuna.

Journal reference:

Mafuna, T., et al. (2022) Comparative Genomics of Listeria Species Recovered from Meat and Food Processing Facilities. Microbiology Spectrum. doi.org/10.1128/spectrum.01189-22.

Research project obtains nearly seven million to study factors that affect human immune system in early life

The first few months and years of life are crucial to the development of the human immune system. This is an important phase as the immune system can define which diseases individuals might develop later in life. INITIALISE, a joint research project of ten universities, will study which environmental factors and mechanisms modify the human immune system in early life and whether targeted interventions could have a positive impact. The project obtained nearly seven million in funding from Horizon Europe.

Research project obtains nearly seven million to study factors that affect human immune system in early life
Professor Matej Orešič. Image Credit: Photographer/Author- Jasper Mattson, Örebro University

The research project is led from the University of Turku and it is coordinated by Professor Matej Orešič, who is also a group leader in the InFLAMES research flagship at the University of Turku, Finland.

The development of the human immune system starts already in the womb and continues after birth once the child is exposed to numerous bacteria, viruses, and other environmental factors. Exposure is important to the development of the immune system, but this stage of development is not without its risks.

“The first few months and years are a very delicate and vulnerable time. We already know that the development of the human immune system in early life is connected to the risks of several diseases later on, particularly allergies, asthma, and autoimmune diseases, such as type 1 diabetes. Yet, the mechanisms of immune imprinting in early life are still poorly understood,” says Professor Matej Orešič.

In a collaboration between ten universities, the INITIALISE project (Inflammation in human early life: targeting impacts on life-course health) will investigate which factors have an impact on the development of the human immune system and what is its significance for people’s health throughout the course of their lives.

A key question is if the immune system be modified so that the risks for different diseases would decrease.    

“Our shared view is that effective early-life interventions targeting the immune system will have a positive impact on life-course health,” says Orešič.

Focus on the impact of chemical exposure

As the immune system starts developing already before birth, the INITIALISE researchers are also interested in the mother’s diet, chemical exposures, and stress during pregnancy. After birth, the intricate interplay of environmental factors and genetics begins and their impact on the development of the immune cells is not yet well understood. In addition, the gut bacteria developed at the beginning of life have an impact on people’s health throughout their entire lifespan.

Furthermore, children have to face the chemical load in their environment with a still developing immune system.

“We are going to study how chemicals impact the immune system. Even a small exposure to chemicals can have significant consequences, and this also applies to other factors that shape our immune system. This is due to the fact that in our first few years, we develop and change quickly and constantly,” Orešič explains. 

INITIALISE mobilises clinicians and scientists with diverse and complimentary expertise in immunology, paediatrics, microbiology, and metabolism. In addition, experts in metabolomics and lipidomics, proteomics, genetics, exposome, psychiatry, systems medicine, and bioinformatics participate in the study. 

Project lasts six years

INITIALISE includes eight prospective and longitudinal birth cohort studies, where the researchers follow groups of children for a long period of time to observe the development of immune-mediated diseases.

Towards the end of the research project, the researchers will conduct a clinical pilot study which aims to discover whether the immune system can be “altered” to prevent the development of diseases.

The clinical trial will target the gut microbiome in at-risk children. Our aim is to improve immune status and reduce disease risk.”

Professor Matej Orešič

The INITIALISE project starts at the beginning of 2023 and lasts six years. In addition to the University of Turku, the member organizations include Örebro University (SE), University of Naples Federico II (IT), Karolinska Institute (SE), University Medical Center Groningen (NL), Linköping University (SE), University of Helsinki (FI), University of Florida (US), Spanish National Research Council (ES), and University of Aberdeen (associated partner, UK).

Deep learning software helps to identify miniscule bacteria in microscopy images

Omnipose, a deep learning software, is helping to solve the challenge of identifying varied and miniscule bacteria in microscopy images. It has gone beyond this initial goal to identify several other types of tiny objects in micrographs.

The UW Medicine microbiology lab of Joseph Mougous and the University of Washington physics and bioengineering lab of Paul A. Wiggins tested the tool. It was developed by University of Washington physics graduate student Kevin J. Cutler and his team.

Mougous said that Cutler, as a physics student, “demonstrated an unusual interest in immersing himself in a biology environment so that he could learn first-hand about problems in need of solution in this field. He came over to my lab and quickly found one that he solved in spectacular fashion.”

Their results are reported in the Oct. 17 edition of Nature Methods.

The scientists found that Omnipose, trained on a large database of bacterial images, performed well in characterizing and quantifying the myriad of bacteria in mixed microbial cultures and eliminated some of the errors that can occur in its predecessor, Cellpose.

Moreover, the software wasn’t easily fooled by extreme changes in a cell’s shape due to antibiotic treatment or antagonism by chemicals produced during interbacterial aggression. In fact, the program showed that it could even detect cell intoxication in a trial using E. coli.

In addition, Omnipose did well in overcoming recognition problems due to differences in the optical characteristics across diverse bacteria.

Most bacteria are spheres or rods, but some have other basic forms, such as twisting spirals. Besides these, Omnipose could identify more elaborate bacteria with elongated shapes or with branches, filaments and appendages, all physical traits that can make it difficult for deep learning tools to suss out which bacteria are present in an image.

The program does still face some limitations in handling object overlap in a 2D rendition of a 3D sample of a crowded microbial community. Object overlap is what produces, for example, the effect of a clock on a wall giving the illusion of popping out of a person’s head in a photograph.

In analyzing cells in a root primordial data set from the fast-growing weed A. thaliana, Omnipose nonetheless did show some advantages over previous approaches in this 3D sample.

Other reviews by the Mougous lab team of Omnipose’s capabilities showed bacteria below a certain threshold in size can be hard for the tool to suss out.

Despite these drawbacks, the researchers believe that Omnipose could be a solution, they noted, to “help answer diverse questions in bacterial cell biology.”

To see if it could also become a multifunctional tool in other biological or even non-life sciences fields dependent on microscopy, the scientists tried out the program on micrographs of the ultra-tiny roundworm C. elegans, an important organism in genetic, neuroscience, developmental and microbial behavior research. Like some bacteria, this creature has an elongated shape. Like many other worms, it also can contort itself. Omnipose could pick out C. elegans regardless of its various stretches, contractions, and other movements. This ability could be useful, for instance, in neural studies of C. elegans locomotion during time-lapse tracking.

In designing tools like Omnipose, researchers are looking at a scale of single-pixel precision to define the boundaries of a cell. That’s because most bacterial cell body images are composed of only a small number of pixels. The researchers explained that defining boundaries within an image is called segmentation. They developed Ominpose through a deep neural-network, high precision segmentation algorithm. Their experiments showed Omnipose has an unprecedented segmentation accuracy.

The scientists designed designed Omnipose for use by typical research laboratories and made its source code, training data and models publicly available, along with documentation on how to use the program.

“We anticipate that the high performance of Omnipose across varied cellular morphologies and modalities,” the researchers wrote in their report,” may unlock information from microscopy images that was previously inaccessible.”

Reflecting the importance of the problem, this is a crowded field. Yet Kevin’s solution stands out from the pack. We believe it will be a game-changer for biological image analysis”

Joseph Mougous, UW Medicine

In addition to Cutler, Wiggins and Mougous, other researchers on the Omnipose testing project were Carsen Stringer, Teresa W. Lo, Luca Rappez, Nicholas Stroustrup. S. Brooke Peterson, and Paul Wiggins. Mougous is a Howard Hughes Medical Institute investigator.

Journal reference:

Cutler, K.J., et al. (2022) Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation. Nature Methods. doi.org/10.1038/s41592-022-01639-4.

Labskin to develop new revolutionary approach to testing for radiation exposure

Labskin is delighted to announce our selection by The Intelligence Advanced Research Projects Activity (IARPA), part of the US Office of the Director of National Intelligence, to join a team of experts to develop new ways to evaluate radiation exposure in civilians and military personnel.

Labskin to develop new revolutionary approach to testing for radiation exposure

Image Credit: Labskin

Labskin is a key member of a consortium selected to develop these technologies in collaboration with a multidisciplinary team of experts including professors from the University of Columbia in New York, Georgetown University in Washington DC, the Georgia Institute of Technology, scientists from the American Type Culture Collection (ATCC) and computer scientists and researchers from the project lead ARETE Associates, a Defense contractor specializing in sensing solution and machine learning algorithms.


In a project worth $800k, starting immediately, Labskin will help develop this technology into minimally invasive testing for radiation for a program known as Targeted Evaluation of Ionizing Radiation Exposure (TEI-REX). TEI-REX aims to develop novel approaches to evaluate organisms exposed to low-dose ionizing radiation. Labskin coupled with Skin Trust Club’s expertise in skin research and microbiology is essential for the project.

The goal of the project is to develop a new biodosimetry standard which could be applied to maintain the safety of military and civilian populations working or living in close proximity to ionizing radiation sources, such as: nuclear plants, nuclear vessels, ammunition, etc. Labskin’s contribution is the creation of a simple non-invasive swab test to collect signatures from the skin surface that allows machine learning algorithms to detect and quantify the impact of any amount of radiation exposure on the skin microbiome.

This is an unique opportunity to revolutionize the way we test for radiation exposure. Labskin and Skin Trust Club are at the forefront of an increasing number of cutting edge technologies that are changing our world. This technique can also be applied to detect the impact of pollution or a variety of chemicals on the environment. Furthermore, this type of testing could not only be used to detect exposure to these kind of events in humans but also in complex ecological systems such as the soil, crops or sediments”

David Caballero-Lima, Chief Scientist, Labskin

We are committed to the success of this very exciting project. The inclusion of Artificial Intelligence and the opportunity to work with ARETE Associates, with their vast experience in complex AI applications, will result in further advances in how AI can be used in conjunction with our skin model at scale. This project coincides with completion of the expansion of our US labs in Delaware, which will greatly help the implementation of this large project. We believe our proven ability to transition technology to the field with Skin Trust Club will be invaluable as we progress this project.”

Colin O’Sullivan, Chief Information Officer, Labskin