Nav: Home

Researchers uncover early adherence step in intestinal transit of Shigella

December 04, 2019

Boston, MA - The bacterial pathogen Shigella, often spread through contaminated food or water, is a leading cause of mortality in both children and older adults in the developing world. Although scientists have been studying Shigella for decades, no effective vaccine has been developed, and the pathogen has acquired resistance to many antibiotics. The recent discovery of an early adherence step in the infection cycle by researchers at Massachusetts General Hospital (MGH) could provide a new therapeutic target or even a new method for vaccine development.

As it moves through the digestive system, Shigella traverses the small intestine and subsequently infects the large intestine, causing cramping, diarrhea and dehydration in the disease called shigellosis. "We wanted to determine how Shigella makes its first contact with epithelial cells in the early stages of disease development," says Dr. Christina Faherty, senior author on the study published in mSphere. "Because of certain gene sequence annotations, and the way that Shigella appeared following growth in standard laboratory media, it was believed that Shigella strains do not produce fimbriae or other adherence factors." Fimbriae are short hair-like fibers that bacterial cells use to adhere to individual epithelial cells to instigate infection.

The work of Faherty and the research team has uncovered evidence of fimbriae that aid adherence to epithelial cells, an important step in the start of a shigellosis infection. "We mimicked the conditions that Shigella would face in its journey through the small intestine by adding bile salts and glucose to laboratory media," says Faherty. "With this method, we discovered what had been hidden in plain sight before--the gene expression profiles that enabled Shigella to initiate this early step in infection by attaching to the epithelial tissue of the host."

Researchers at the Mucosal Immunology and Biology Research Center at MGH performed comprehensive microscopy and genetic analyses of Shigella to determine its subsequent steps after leaving the stomach. Their results demonstrate that "at least three structural genes facilitate S. flexneri (strain) 2457T adherence for epithelial cell contact and biofilm formation." In other words, their findings contradict the current hypothesis that critical components in the gene clusters are unable to produce fimbriae or other adherence factors.

In earlier research, Faherty and colleagues determined that exposure to bile salts resulted in the formation of biofilms, a protective coating of bacterial communities. Faherty hypothesizes that this coating enables the pathogen to survive the harsh conditions of the small intestine to successfully enter the colon. Since biofilm formation requires adherence factors, and since bacterial cells dispersed from the biofilm adhere better to epithelial cells, the next step by the group was to investigate adherence factor expression under these conditions. This next step was indeed controversial given the hypotheses that Shigella does not produce adherence structures; yet, the comprehensive analyses provided strong evidence to the contrary.

Co-author Rachael Chanin notes that the group's most recent study confirms their earlier analyses that the "in vivo-like" conditions facilitated biofilm formation and adherence to epithelial cells through fimbriae attachment. "One of the main challenges in studying Shigella is the lack of animal models that faithfully recapitulate human disease," says Chanin. "Although there have been elegant and thorough studies of what happens when the pathogen enters colonic epithelial cells, we did not understand what happens during transit through the digestive system or how the bacterium approaches or interacts with host cells prior to entry. Our work begins to address these questions and underlines the importance of in vivo-like culture methods. It also shows that these methods may influence our experimental results--whether intentionally or unintentionally."

After the promising results from their bile salts and glucose laboratory model, the researchers added another component to their adherence analysis--a human intestinal organoid. The "mini-gut," created from stem cells isolated from intestinal tissue, represents a model of the human intestinal epithelium. Working with a mini-gut of the ascending colon, the researchers discovered the Shigella adherence structures making initial contact with epithelial cells. "We think these adherence factors used in the intestinal organoid model replicate the contact made with the epithelial cells in the colon in the initial stages of shigellosis," says Faherty.
-end-


Massachusetts General Hospital

Related Infection Articles:

Sensing infection, suppressing regeneration
UIC researchers describe an enzyme that blocks the ability of blood vessel cells to self-heal.
Boost to lung immunity following infection
The strength of the immune system in response to respiratory infections is constantly changing, depending on the history of previous, unrelated infections, according to new research from the Crick.
Is infection after surgery associated with increased long-term risk of infection, death?
Whether experiencing an infection within the first 30 days after surgery is associated with an increased risk of another infection and death within one year was the focus of this observational study that included about 660,000 veterans who underwent major surgery.
Revealed: How E. coli knows how to cause the worst possible infection
The discovery could one day let doctors prevent the infection by allowing E. coli to pass harmlessly through the body.
UK study shows most patients with suspected urinary tract infection and treated with antibiotics actually lack evidence of this infection
New research presented at this week's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (April 13-16, 2019) shows that only one third of patients that enter the emergency department with suspected urinary tract infection (UTI) actually have evidence of this infection, yet almost all are treated with antibiotics, unnecessarily driving the emergence of antimicrobial resistance.
Bacteria in urine doesn't always indicate infection
Doctors should think carefully before testing patients for a urinary tract infection (UTI) to avoid over-diagnosis and unnecessary antibiotic treatment, according to updated asymptomatic bacteriuria (ASB) guidelines released by the Infectious Diseases Society of America (IDSA) and published in Clinical Infectious Diseases.
Subsidies for infection control to healthcare institutions help reduce infection levels
Researchers compared three types of infection control subsidies and found that under a limited budget, a dollar-for-dollar matching subsidy, in which policymakers match hospital spending for infection control measures, was the most effective at reducing the number of hospital-acquired infections.
Dengue virus infection may cause severe outcomes following Zika virus infection during pregnancy
This study is the first to report a possible mechanism for the enhancement of Zika virus progression during pregnancy in an animal model.
How common is Hepatitis C infection in each US state?
Hepatitis C virus infection is a major cause of illness and death in the United States and injection drug use is likely fueling many new cases.
The medicine of the future against infection and inflammation?
Researchers at Lund University in Sweden, have in collaboration with colleagues in Copenhagen and Singapore, mapped how the body's own peptides act to reduce infection and inflammation by deactivating the toxic substances formed in the process.
More Infection News and Infection 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

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.