Bacterial species

Algorithm Identifies Dozens of New Bacterial Species from Clinical Isolates

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Bacteria

Growth of bacterial cultures in Petri dishes [Sylvia Suter, University Hospital Basel]

Clinical bacteriology relies on the ability to identify cultured isolates. However, unknown isolates are common in hospital settings. Now, researchers at the University of Basel, have established a new study algorithm—NOVA (Novel Organism Verification and Analysis)—to analyze bacterial isolates that cannot otherwise be characterized using conventional identification procedures.

This work is published in BMC Microbiology in the paper, “Novel Organism Verification and Analysis (NOVA) study: Identification of 35 clinical isolates representing potentially novel bacterial taxa using a pipeline based on whole genome sequencing.”

The team, which has been collecting and analyzing patient samples containing unknown bacterial isolates since 2014, have discovered more than thirty new species of bacteria, some of which are associated with clinically relevant infections.

In this work, the researchers led by Daniel Goldenberger, PhD, at the University of Basel, analyzed 61 unknown bacterial pathogens found in blood or tissue samples from patients with a wide range of medical conditions. Conventional laboratory methods, such as mass spectroscopy or sequencing a small part of the bacterial genome, had failed to produce results for all these isolates. Researchers sequenced the complete genome of the bacteria.

Out of 61 analyzed bacteria, 35 represent potentially novel species. And 27 of 35 strains were isolated from deep tissue specimens or blood cultures. The authors noted that, “Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus.”

Most of the newly identified species belong to the Corynebacterium and Schaalia genera, both gram-positive bacilli. “Many species in these two genera are found in the natural human skin microbiome and the mucosa. This is why they are frequently underestimated, and research into them is sparse,” explained Goldenberger. They can, however, cause infections when they enter into the bloodstream—due to a tumor, for example.

The researchers classified the remaining 26 strains as hard to identify. An evaluation of the patient data showed that seven out of the 35 new strains were clinically relevant, meaning that they can cause bacterial infections in humans. “Such direct links between newly identified species of bacteria and their clinical relevance have rarely been published in the past,” said Goldenberger.

One of the hard-to-identify pathogens might be clinically relevant, too. It was found in the inflamed thumb of a patient after a dog bite. A Canadian research group also recently isolated this bacterium from wounds caused by dog or cat bites. “This has led us to assume that it is an emerging pathogen which we need to monitor,” said Goldenberger. The Canadian researchers appropriately named the bacterium Vandammella animalimorsus (animal bite Vandammella) in 2022.

Naming their new species is the next item on the Basel team’s to-do list, too. They are working closely with Peter Vandamme, a professor from the University of Ghent and a specialist in bacteria classification. Two of the bacteria have been named already. One is Pseudoclavibacter triregionum—referring to Basel’s location near the borders of Switzerland, France, and Germany.

New algorithm identifies gene transfers between different bacterial species

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Mosaic pneumococcal population structure caused by horizontal gene transfer is shown on the left for a subset of genes. Matrix on the right shows a genome-wide summary of the relationships between the bacteria, ranging from blue (distant) to yellow (closely related). Credit: Pekka Marttinen

Gene transfers are particularly common in the antibiotic-resistance genes of Streptococcus pneumoniae bacteria.

When mammals breed, the genome of the offspring is a combination of the parents’ genomes. Bacteria, by contrast, reproduce through cell division. In theory, this means that the genomes of the offspring are copies of the parent genome. However, the process is not quite as straightforward as this due to horizontal gene transfer through which bacteria can transfer fragments of their genome to each other. As a result of this phenomenon, the genome of an individual bacterium can be a combination of genes from several different donors. Some of the genome fragments may even originate from completely different species.

In a recent study combining machine learning and bioinformatics, a new computational method was developed for modelling gene transfers between different lineages of a bacterial population or even between entirely different bacterial species. The method was used to analyse a collection of 616 whole-genomes of a recombinogenic pathogen Streptococcus pneumoniae.

The usefulness of a gene affects its transfer rate

In the study, several individual genes in which gene transfers were considered particularly common were identified. These genes also included genes causing resistance to antibiotics.

‘In the case of antibiotic-resistance genes, the number of gene transfers may be related to how useful these genes are to bacteria and to the resulting selection pressure’, says Academy Research Fellow Pekka Marttinen from the Aalto University Department of Computer Science.

‘The study will not provide a direct solution to antibiotic resistance because this would require a profound understanding of how the resistance occurs and spreads. Nevertheless, knowing the extent to which gene transfer occurs between different species and lineages can help in improving this understanding’, he explains.

The study was able to show that gene transfer occurs both within species and between several different species. The large number of transfers identified during the study was a surprise to the researchers.

‘Previous studies have shown that gene transfers are common in individual genes, but our team was the first to use a computational method to show the extent of gene transfer across the entire genome‘, Marttinen says.

‘The method also makes it possible to effectively examine ancestral gene transfers for the first time, which is important in examining transfers between different species.’

DO GUT BACTERIA RULE OUR MINDS?

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It sounds like science fiction, but it seems that bacteria within us — which outnumber our own cells about 100-fold — may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.

In an article published this week in the journal BioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.

Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem — our digestive tracts — they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.

While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the gut microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.

“Bacteria within the gut are manipulative,” said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.

Fortunately, it’s a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.

Our diets have a huge impact on microbial populations in the gut,” Maley said. “It’s a whole ecosystem, and it’s evolving on the time scale of minutes.”

There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.

Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.

“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” said Aktipis, who is currently in the Arizona State University Department of Psychology.

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In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.

Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?

The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.

“Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating,” the authors wrote.

The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago. Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.

In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.

“Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health,” she said.