Viruses are teeming on your toothbrush, showerhead

 

Step aside tropical rainforests and coral reefs -- the latest hotspot to offer awe-inspiring biodiversity lies no further than your bathroom.

In a new Northwestern University-led study, microbiologists found that showerheads and toothbrushes are teeming with an extremely diverse collection of viruses -- most of which have never been seen before.

Although this might sound ominous, the good news is these viruses don't target people. They target bacteria.

The microorganisms collected in the study are bacteriophage, or "phage," a type of virus that infects and replicates inside of bacteria. Although researchers know little about them, phage recently have garnered attention for their potential use in treating antibiotic-resistant bacterial infections. And the previously unknown viruses lurking in our bathrooms could become a treasure trove of materials for exploring those applications.

The study will be published Wednesday (Oct. 9) in the journal Frontiers in Microbiomes.

"The number of viruses that we found is absolutely wild," said Northwestern's Erica M. Hartmann, who led the study. "We found many viruses that we know very little about and many others that we have never seen before. It's amazing how much untapped biodiversity is all around us. And you don't even have to go far to find it; it's right under our noses."

An indoor microbiologist, Hartmann is an associate professor of civil and environmental engineering at Northwestern's McCormick School of Engineering and a member of the Center for Synthetic Biology.

The return of 'Operation Pottymouth'

The new study is an offshoot of previous research, in which Hartmann and her colleagues at University of Colorado at Boulder characterized bacteria living on toothbrushes and showerheads. For the previous studies, the researchers asked people to submit used toothbrushes and swabs with samples collected from their showerheads.

Inspired by concerns that a flushing toilet might generate a cloud of aerosol particles, Hartmann affectionately called the toothbrush study, "Operation Pottymouth."

"This project started as a curiosity," Hartmann said. "We wanted to know what microbes are living in our homes. If you think about indoor environments, surfaces like tables and walls are really difficult for microbes to live on. Microbes prefer environments with water. And where is there water? Inside our showerheads and on our toothbrushes."

Diversity and opportunities

After characterizing bacteria, Hartmann then used DNA sequencing to examine the viruses living on those same samples. She was immediately blown away. Altogether, the samples comprised more than 600 different viruses -- and no two samples were alike.

"We saw basically no overlap in virus types between showerheads and toothbrushes," Hartmann said. "We also saw very little overlap between any two samples at all. Each showerhead and each toothbrush is like its own little island. It just underscores the incredible diversity of viruses out there."

While they found few patterns among all the samples, Hartmann and her team did notice more mycobacteriophage than other types of phage. Mycobacteriophage infect mycobacteria, a pathogenic species that causes diseases like leprosy, tuberculosis and chronic lung infections. Hartmann imagines that, someday, researchers could harness mycobacteriophage to treat these infections and others.

"We could envision taking these mycobacteriophage and using them as a way to clean pathogens out of your plumbing system," she said. "We want to look at all the functions these viruses might have and figure out how we can use them."

Most microbes 'will not make us sick'

But, in the meantime, Hartmann cautions people not to fret about the invisible wildlife living within our bathrooms. Instead of grabbing for bleach, people can soak their showerheads in vinegar to remove calcium buildup or simply wash them with plain soap and water. And people should regularly replace toothbrush heads, Hartmann says. Hartmann also is not a fan of antimicrobial toothbrushes, which she said can lead to antibiotic-resistant bugs.

"Microbes are everywhere, and the vast majority of them will not make us sick," she said. "The more you attack them with disinfectants, the more they are likely to develop resistance or become more difficult to treat. We should all just embrace them."

The study, "Phage communities in household-related biofilms correlate with bacterial hosts but do not associate with other environmental factors," was supported by Northwestern University.

Journal Reference:

1. Stefanie Huttelmaier, Weitao Shuai, Jack T. Sumner, Erica M. Hartmann. Phage communities in household-related biofilms correlate with bacterial hosts. Frontiers in Microbiomes, 2024; 3 DOI: 10.3389/frmbi.2024.1396560 

Courtesy:

Northwestern University. "Viruses are teeming on your toothbrush, showerhead." ScienceDaily. ScienceDaily, 9 October 2024. <www.sciencedaily.com/releases/2024/10/241009122630.htm>.

 

 

 

 

Large-scale atlas of how immune cells react to mutations during cancer immunotherapy

 

A Cleveland Clinic-led research collaboration between Timothy Chan, MD, PhD, Chair of Cleveland Clinic's Global Center for Immunotherapy, and Bristol Myers Squibb has published the most comprehensive overview to date of how the immune system reshapes tumor architecture in response to immune checkpoint therapy.

The eight-year study, published in Nature Medicine, outlines how cancer immunotherapy induces tumor recognition through neoantigens to reshape the tumor ecosystem. Neoantigens are small peptides produced when cancer cells mutate and are a primary marker for the immune system to recognize cancer cells as different from self.

"This study is unique in that we sampled tumors prior to therapy and then early after immunotherapy was initiated," explains Dr. Chan, who is also chair of Cleveland Clinic's Center for Immunotherapy & Precision Immuno-Oncology, program leader of Case Comprehensive Cancer Center's Immune Oncology Program and the Sheikha Fatima bint Mubarak Endowed Chair in Immunotherapy. "Our goal was to understand how patients' tumors are recognized and altered by their immune system in response to immunotherapy."

Our immune cells and cancer cells constantly interact and influence one another over the course of cancer. Immunotherapy treatments need to operate within that framework by boosting our immune cells to eliminate cancer. Scientists like Dr. Chan have begun to untangle the complex relationships between treatment, immunity and cancer in the past 15 years -- but human data is in short supply.

The CheckMate-153 trial was overseen by pharmaceutical company Bristol Myers Squibb and Dr. Chan's team was a central site for the trial's analysis. Within the primary trial, investigators included a biomarker sub-study to identify how neoantigens drive response to nivolumab by sampling patients' tumors pre-therapy and 3 weeks post-therapy. From these tumor samples, sequencing was used to identify mutations that create neoantigens.

Neoantigens are thought to be the primary way that the immune system recognizes tumors, but neoantigen prediction tools lack accuracy due to lack existing data in this space. To overcome this issue the team developed the largest neoantigen screen to date, where they validated their predictions and monitored the dynamic response to neoantigens with longitudinal blood draws.

Within three weeks of treatment, people who went on to respond well to nivolumab had a sharp decline in clonal neoantigens. Meanwhile, individuals whose cancer did not go into remission still mounted an immunologic response but to smaller sub-clonal populations. This is important because many believed that non-responders were unable to activate and recognize tumor, but here they show it may be that the immune system is mounting a response to neoantigens but that this is insufficient to destroy all tumor clones.

Current neoantigen prediction tools rely heavily on HLA-binding neoantigens, but they are missing the T cell recognition aspect of immunogenicity, says Cleveland Clinic's co-first author Tyler Alban, PhD, Project Staff in the Chan Lab. Dr. Alban, data scientist Prerana Parthasarathy, and others on the team developed a machine-learning program that uses the new screening data to better predict immunogenic neoantigens. In the process, the program identified novel features harbored by these cancer-derived neoantigens.

"We observed a whole ecosystem of immune cells at work, with each T cell recognizing a different neoantigen altering the clonal makeup of the tumor," Dr. Alban says. "Our data let us generate new insights into neoantigens and resistance to immunotherapy."

By cataloguing changes to neoantigens during treatment, Dr. Alban's analyses challenged the prevailing theory in immunotherapy: that a tumor only needs one lucky mutation to develop features our immune systems recognize as a threat. The results show that many different T cells recognizing many different cancer-causing features are needed to respond well to treatment.

Roadmaps generated by these types of observational studies will be critical in navigating future immuno-oncology research, Dr. Chan says.

"Learning why our immune systems respond to some cancerous mutations but not others are like the holy grail for immunotherapy researchers," he explains. "Our findings are one of the closest things we have to figuring these things out."

The group is also using their dataset in collaboration with IBM in the Cleveland Clinic -- IBM Discovery Accelerator to more advanced AI models that predict new molecules for cancer treatments and cancer vaccine development.

Journal Reference:

1. Tyler J. Alban, Nadeem Riaz, Prerana Parthasarathy, Vladimir Makarov, Sviatoslav Kendall, Seong-Keun Yoo, Rachna Shah, Nils Weinhold, Raghvendra Srivastava, Xiaoxiao Ma, Chirag Krishna, Juk Yee Mok, Wim J. E. van Esch, Edward Garon, Wallace Akerley, Benjamin Creelan, Nivedita Aanur, Diego Chowell, William J. Geese, Naiyer A. Rizvi, Timothy A. Chan. Neoantigen immunogenicity landscapes and evolution of tumor ecosystems during immunotherapy with nivolumab. Nature Medicine, 2024; DOI: 10.1038/s41591-024-03240-y 

Courtesy:

Cleveland Clinic. "Large-scale atlas of how immune cells react to mutations during cancer immunotherapy." ScienceDaily. ScienceDaily, 1 October 2024. <www.sciencedaily.com/releases/2024/10/241001152944.htm>.