Nav: Home

Cholera studies reveal mechanisms of biofilm formation and hyperinfectivity

April 20, 2020

Free-swimming cholera bacteria are much less infectious than bacteria in biofilms, aggregates of bacterial cells embedded in a sticky matrix that form on surfaces. This accounts for the surprising effectiveness of filtering water through cloth, such as a folded sari, which can reduce infections dramatically in places where the disease is endemic, despite the fact that individual cholera bacteria easily pass through such a filter.

A new study led by researchers at UC Santa Cruz goes a long way toward explaining the hyperinfectivity of cholera biofilms. The study, published the week of April 20 in the Proceedings of the National Academy of Sciences (PNAS), is one of several new papers on cholera biofilms from the laboratory of UCSC microbiologist Fitnat Yildiz.

"We've been working on this for so long, it is a significant body of work that is now being published, focusing on the mechanisms of biofilm formation and what makes the biofilm more infectious," said Yildiz, a professor of microbiology and environmental toxicology.

Biofilms are important not only in causing infections, but also in the survival of cholera bacteria (Vibrio cholerae) in the environment. In regions where cholera is endemic, the bacteria live in aquatic environments, typically in brackish water, causing periodic, seasonal outbreaks when sources of drinking water become contaminated.

A surprising finding in the PNAS paper is that bacteria growing in biofilms have already activated the genes for virulence factors such as toxin production, before they have even infected a host.

"Two of the main virulence factors are the toxin co-regulated pilus, which allows the bacteria to adhere to the intestine, and the cholera toxin which enters intestinal cells and makes people really sick," said Jennifer Teschler, a postdoctoral researcher in the Yildiz lab and a co-first author of the paper. "These virulence factors are more highly expressed in biofilm cells, so they are already primed for causing infections."

The study also showed differences in the colonization patterns of free-swimming ("planktonic") and biofilm-grown cholera cells in the intestines of infected mice. The researchers used a new imaging technique to make intestinal tissue transparent while preserving the spatial integrity of the infected intestines. This enabled them to see where the cholera bacteria had adhered to the villi, the finger-like projections that line the small intestine.

"Being able to see where the infections are in three dimensions is an important tool for studying intestinal pathogens," Teschler said. "In mice infected with planktonic cells, the cells were typically at the bottom of the villi, whereas biofilm cells attached at the top of the villi, closer to the lumen. We speculate that biofilm cells adhere more strongly to the villi, so they are better able to resist being swept away by the flow in the lumen of the intestine."

Two other papers, published March 25 in Nature Communications and March 16 in PLOS Genetics, focus on how free-swimming cholera bacteria attach to surfaces and initiate biofilm formation.

"The bacterium has to attach to a surface, stop swimming, and start building a matrix," Yildiz said. "Understanding the mechanisms involved in biofilm formation, as well as the role of biofilms in the overall biology of Vibrio cholerae, will pave the way for developing strategies to predict and control cholera epidemics. It may also help in identification of novel drug targets for inhibiting biofilm formation during infection."

The Nature Communications paper explores the cellular signaling pathways that control the attachment process through the regulation of hair-like appendages called pili that grow out from the cell surface.

"Attachment is the initiating step of biofilm formation," explained first author Kyle Floyd, a postdoctoral researcher in the Yildiz lab. "As a swimming cell nears a surface, the pilus will bind to the surface, and retraction of the pilus helps pull the cell closer to the surface. The cell then makes more pili to anchor it down to the surface."

There are different classes and subclasses of bacterial pili, and the one required for biofilm formation in many Vibrio cholerae strains (the type IV MSHA pilus) is regulated by a signaling molecule called c-di-GMP. The new study showed that the MSHA pilus is a dynamic system that extends and retracts and is directly controlled by c-di-GMP. The study showed how pilus activity is modulated by the interactions of c-di-GMP with other components of the pilus system.

The PLOS Genetics paper further elucidates the c-di-GMP signaling pathways that promote biofilm formation. In particular, the study looked at the role of the flagellum, a whip-like appendage the bacteria use to swim, in c-di-GMP signaling. The researchers found that loss of the flagellum leads to elevated levels of c-di-GMP in the cell and increased expression of biofilm genes.

"It required powerful and elegant genetics to work out the connections between flagellum assembly, production of pili on the cell surface, biofilm matrix production, and c-di-GMP signaling," Yildiz said. "There are different steps where this signaling molecule can control the transition to biofilm formation."
-end-
All three papers involved extensive collaboration with researchers at other institutions. The coauthors of the PNAS paper, in addition to Yildiz and Teschler, include co-first authors Ana Gallego-Hernandez and Jinhwan Park at UCSC and William DePas at the California Institute of Technology; Raimo Hartmann, Hannah Jeckel, and Knut Drescher at the Max Planck Institute for Terrestrial Microbiology in Germany; Sinem Beyhan at the J. Craig Venter Institute; and Dianne Newman at Caltech. This work was funded by the National Institutes of Health.

University of California - Santa Cruz

Related Bacteria Articles:

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.
Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.
Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.
Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.
Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.
Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.
How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.
The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?
Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.
Bacteria uses viral weapon against other bacteria
Bacterial cells use both a virus -- traditionally thought to be an enemy -- and a prehistoric viral protein to kill other bacteria that competes with it for food according to an international team of researchers who believe this has potential implications for future infectious disease treatment.
More Bacteria News and Bacteria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.