One member of a large protein family that is known to stop the spread of bacterial infections by prompting infected human cells to self-destruct appears to kill the infectious bacteria instead, a new study led by UT Southwestern scientists shows. However, some bacteria have their own mechanism to thwart this attack, nullifying the deadly protein by tagging it for destruction.
The findings, published online on May 21/21 in Cell, could lead to new antibiotics to fight bacterial infections. And insight into this cellular conflict could shed light on a number of other conditions in which this protein is involved, including asthma, Type 1 diabetes, primary biliary cirrhosis, and Crohn’s disease.
Previous research has shown that the protein, called gasdermin B (GSDMB), was different from other members of the mammalian gasdermin family. Related gasdermin proteins form pores in the membranes of infected cells, killing them while allowing inflammatory molecules to leak out and incite an immune response. However, GSDMB – found in humans but not in some other mammalian species, including rodents – doesn’t form pores in the membranes of cultured mammalian cells, leaving its target a mystery.
Using a novel screening technology, Alto and colleagues discovered that a protein toxin called IpaH7.8 from shigella flexneri, a bacterium that causes diarrheal disease, directly inhibits GSDMB. Biochemical experiments show that IpaH7.8 places a chemical tag on GSDMB that marks it for cellular destruction.
To understand why shigella flexneri rids human cells of GSDMB, the researchers placed GSDMB within synthetic mammalian and bacterial cell membranes. While GSDMB left the synthetic mammalian membranes unharmed, it poked holes in the bacterial membranes. Further investigation showed that immune cells called natural killer cells stimulate this process.
Alto notes that inhibiting the ability of shigella IpaH7.8 to counteract GSDMB could lead to new types of antibiotics. And because genetic variants of GSDMB have been linked to a variety of inflammatory diseases and cancer, better understanding this protein could lead to new treatments for these conditions too.
An outbreak of Shigella in England in 2018 was most likely caused by coriander that was contaminated, according to researchers from the journal Epidemiology and Infection.
Food Safety Magazine reports that in April 2018, Public Health England was informed of cases of Shigella sonnei, of people who had eaten food from three different catering outlets. Initially, the outbreaks were investigated separately, but whole-genome sequencing (WGS) showed that they were caused by the same strain.
Epidemiological data was analyzed, as well as the food chain and microbiological examination of food samples. WGS was used to determine the phylogenetic relatedness and antimicrobial resistance profile of the outbreak strain.
Thirty-three cases were linked to the outbreak, and the majority of people involved had eaten food from seven outlets specializing in Indian or Middle Eastern cuisine. Five outlets were linked to two or more cases, all of which used fresh coriander, although a shared supplier was not able to be identified. An investigation at one of the outlets found that 86 percent of cases reported eating dishes with coriander, either as an ingredient or a garnish. Four cases were admitted to the hospital, and one had evidence of treatment failure with ciprofloxacin.
Phylogenetic analysis proved that the outbreak was part of a wider, multidrug-resistant group of organisms, associated with travel to Pakistan. Likely contributing factors were poor hygiene practices during cultivation, distribution, or preparation of fresh produce.
Enteroinvasive Escherichia coli (EIEC) and Shigella spp. are both Gram-negative bacteria causing diarrheal disease worldwide [1,2]. The clinical presentations of these two pathogens are very similar [3,4] and commonly manifested through diarrhoea, abdominal cramps, nausea and fever both in children and adults [5,6]. In addition to a similar clinical picture, EIEC and Shigella share laboratory features that can make it difficult to distinguish between them in routine clinical laboratory practice. Both pathogens are transmitted via the faecal-oral route and infections are frequently associated with consumption of contaminated food and water [7–10]. While Shigella is associated with large-scale food-borne outbreaks [11,12], outbreaks caused by EIEC are rarely recorded.
High prevalence of EIEC infections have been documented in rural areas and settings with poor sanitation in high-risk countries [5,13] while EIEC infections in Europe are typically sporadic and travel related [14]. Nevertheless, a few EIEC outbreaks have been reported in Europe, with the most recent ones having occurred in Italy in 2012 [15] and in the United Kingdom (UK) in 2014 [16]. These outbreaks affected 109 cases and 157 probable cases, respectively, highlighting the fact that EIEC, like Shigella, has the capacity to cause large gastrointestinal disease outbreaks. The outbreak strain identified in these recent European outbreaks, EIEC O96:H19, is an emergent type of EIEC that has phenotypic characteristics more resembling those of non-invasive Escherichia coli (E. coli) than those described for Shigella [17]. These characteristics are suggested to contribute to improved survival abilities as well as the ability to better adapt to different ecological niches [17].
Traditionally, culturing of faecal specimens has been the mainstay of laboratory diagnostics for enteric bacteria, and EIEC has been differentiated from Shigella by assessing a combination of several phenotypic characteristics, including biochemical, motility and serological traits [18,19]. This is now changing as PCR-based methods are becoming routine in many diagnostic laboratories [20]. In contrast to non-invasive E. coli, EIEC and Shigella can invade and multiply in intestinal epithelial cells [21], a process that is partially mediated by the products of the invasion plasmid antigen (ipa) genes [22]. For this reason, PCR targeting the ipaH gene can separate EIEC from other non-invasive E. coli, but cannot differentiate between EIEC and Shigella [23]. The lacY gene has been proposed as an additional molecular marker for which most E. coli are positive and Shigella is negative [24]. Its use as a PCR target in separating Shigella and EIEC is restricted to bacterial isolates since many faecal samples are lacY positive because of the presence of E. coli in the normal flora.
Which is considered too time consuming for most clinical laboratories. For this reason, it is likely that a patient with specimens that are ipaH PCR-positive but culture negative would not be notified as a case if the diagnostic algorithm at the laboratory requires a detected Shigella isolate. In addition, PCR is a more sensitive method than culturing [25] and Shigella is known for its limited survival ability in faecal samples [26], which also may lead to samples being ipaH PCR-positive but culture negative.
Shigellosis is notifiable by law in Sweden as in the majority of countries in Europe [27]. In 2017, the incidence was 2.1 per 100,000 inhabitants in Sweden, and the majority of cases had been infected abroad [28]. The mandatory reporting of diseases allows the implementation of a series of public health actions, including public health management and surveillance activities, and helps define risk exposures. In contrast to shigellosis, reporting is not mandatory for EIEC and the occurrence of this pathogen in Sweden is currently unknown.It requires additional laboratory procedures such as screening large numbers of colonies,
Outbreak of gastroenteritis highlighting the diagnostic and epidemiological challenges of enteroinvasive Escherichia coli, county of Halland, Sweden, November 2017, 12 December 2019
I had this prof back in my undergraduate genetics days who prayed at the church of RNA.
He may have been right.
He was an asshole.
MicroRNAs are small RNA molecules that do not code for proteins, however, they take care of an essential function: they act as regulators in gene expression, and so they have become a focus of attention for medical science. Despite there being thousands of different sequences of this genetic material, the individual role that each one plays in several illnesses continues to be unknown for the most part.
Recently, research done at the University of Cordoba, among other places, and published in Nature Microbiology, was able to determine the specific function of certain microRNAs in Salmonella Typhimurium and Shigella flexneri infections. These are two similar bacteria that are passed on to humans upon ingesting food or water infected by people or animals with the disease.
These are two intracellular pathogens that invade healthy cells and cause similar symptoms. Nevertheless, in spite of their many similarities, the results show that infections from these two bacteria are controlled by different microRNAs that have a radically opposite function.
In order to come to this conclusion, an array of over 1,400 different microRNAs were studied individually so as to verify what effect they produce in cells upon being infected by these two bacteria, explains University of Cordoba Genetics Department researcher Sara Zaldívar.
In the case of Shigella, the results show that upon infection, three specific kinds of microRNA silence the expression of the gene responsible for spreading the bacteria within the infected organism by means of filaments called filopodia. This is an immune response mechanism of the infected organism that, as a result, lessens the bacteria’s movement.
In the case of Salmonella, almost the opposite occurs. Once the cell is infected, a kind of microRNA activates the expression of a gene responsible for the bacteria reproducing. This is the pathogen’s attack mechanism in order to reproduce, something that was not only demonstrated in the laboratory but also was corroborated in vivo in pig intestinal mucosa.
The results show two mechanisms of how microRNAs act in completely different ways and that were not described ever before. While in some infections, such as Shigella, these small molecules of genetic material perform a function in the immune response of the infected organism, in others, like Salmonella, they are part of the strategies developed by the bacterium to benefit itself in order to reproduce.
One of the main takeaways from the research, as pointed out by another author, Professor Juan José Garrido, is the need to understand the specific response mechanisms of each pathogen so as to not err by extrapolating treatment. “If we do not know exactly how microRNA regulation works, then we are blindly assigning treatment and we will end up haphazardly using a wide range of antibiotics that build up resistance to the bacteria”, says the researcher. “In our laboratory alone”, adds Sara Zaldívar, “we have strains of Salmonella that have built up resistance to 14 different antibiotics”. For this reason, knowing about the mechanisms of each pathogen in particular is key to developing more effective drugs by means of searching for target genes involved in the process.
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.”
My cousin of Barrie’s Asparagus is in the midst of the annual crop in southern Ontario, and I know they have good food safety because my students have checked them out in years past and, I’m his cousin.
Unfortunately not all growers are as diligent and any commodity can get branded as shit.
Specifically, Shigella shit.
Findings presented at the CDC’s Epidemic Intelligence Service, or EIS, conference last month found that contaminated asparagus was the likely source of an outbreak of shigellosis at a wedding party in Oregon that sickened 112 people.
The outbreak was caused by Shigella flexneri type 3a, which accounts for less than 3% of S.flexneri isolates in the United States, researchers said.
“This was one of the largest foodborne outbreaks of shigellosis in U.S. history,” Steven I. Rekant, DVM, MPH, an EIS officer with the Oregon Public Health Authority, said in a presentation. “It was the second largest ever attributed to Shigella flexneri and that type of Shigella flexneri, type 3a, is uncommon in Oregon.”
According to Rekant and colleagues, the Oregon Health Authority received reports of gastroenteritis among attendees at a wedding in August 2018 and identified S. flexneri type 3a in stool samples.
A total of 263 people attended the wedding, and 75% responded to the survey. The patients were aged 2 to 93 years, and 55% were female.
“Simply put, this was big outbreak — 112 cases were reported, with an overall attack rate of 55.7%,” Rekant said.
Of 95 patients with onset information, 97% reported illness 12 to 72 hours following the wedding. Additionally, 57 patients presented to a health care facility and 10 were hospitalized, including a 92-year-old woman. No deaths or additional cases were reported.
The investigators found that only asparagus consumption was associated with illness.
They pointed to poor hygiene on the part of the food-handler as the “likely cause of contamination.”
Rekant SI, et al. Shigellosis at a Wedding — Oregon, 2018. Presented at: Epidemic Intelligence Service conference; April 29-May 2, 2019; Atlanta.
It reveals for the first time that these proteins can detect where bacteria will split for division and prevent it from doing so by forming cage-like structures around the bacteria.
The research team say that although septins are a powerful, natural mechanism to restrict Shigella, future work is required to determine how septin biology can be harnessed for therapeutic purposes. It is hoped that these new findings may lead to a novel way to boost the human immune system and treat a wide variety of bacterial infections.
Lead author Professor Serge Mostowy from the London School of Hygiene & Tropical Medicine said: “We are actively working to engineer this discovery for human health application. If we can use drugs to boost septin caging, we have a new way to stop infection.”
In 2010, researchers first observed that septin cages can entrap Shigella, opening up the tantalising prospect of a new way to stop the bacteria spreading in the body. However, how cells recognise Shigella for entrapment, and the fate of entrapped bacteria, was mostly unknown.
The authors acknowledge limitations of the study including the possibility that some bacteria have evolved to avoid septin cage entrapment, and the need for in vivo study prior to application in humans.
Sure I get social aspect, the trying different foods and experiencing different cultures.
But do I trust the different food prep places, proper temperatures, storage and cleanliness.
Jane Wester of the Charlotte Observer reports at least 40 people are sick after eating contaminated food at a potluck birthday party in east Charlotte Saturday, Mecklenburg County health department officials said Monday.
Someone who prepared food for the party did not wash their hands well enough, Health Director Gibbie Harris said. Some partygoers are infected with a “highly contagious” disease called shigella, which causes diarrhea and is spread through feces, Harris said.
About 100 people attended the birthday party, and more may still get sick, as symptoms of shigella can take one to three days to show up after someone is infected, Communicable Disease Control director Carmel Clements said. It’s possible, however, for some people to get sick a whole week later, Clements said.
Most patients called 911 from the Forest Hills apartment complex, near where the party was held, according to Medic.
Health officials are sure that the contaminated dish was prepared in someone’s home rather than a restaurant, Harris said, because the only outside food at the party was the birthday cake.
Most of us are taught from a very early age that hand-washing is an easy, essential way of keeping ourselves clean and healthy. But residents of Flint, Michigan and surrounding areas have been forgoing this common practice out of fear of the water’s toxicity. Genesee county, of which Flint is a the largest city, and the adjacent county of Saginaw combined have experienced an outbreak of 131 cases of Shigellosis (named after the bacteria that causes it, Shigella). It’s a bloody diarrheal disease transmitted via tiny amounts of contaminated fecal matter. It typically lasts about a week, but can also cause patients to feel like they have to go to the bathroom even when they have no more waste in their systems. Additionally, the US Centers for Disease Control (CDC) also notes that “may be several months before [patients] bowel habits are entirely normal.”
In 2013, there were just under five cases reported per every 100,000 people in America. The outbreak in Michigan far exceeds that number, and it’s likely because residents in the area are afraid to use their tap water, which was found to have toxic levels of lead, a heavy metal that can cause neurological problems when it builds up in the body, in 2015. Even though the water was deemed safe for consumption with a proper filter, people in the area are still scared to wash their hands at all, according to the Washington Post.
Instead, they’re cleaning themselves using baby wipes—aren’t nearly as effective as disinfectant as good old-fashioned scrubbing—which should take about 20 seconds to ensure that any potential pathogens are washed down the drain.
“Some people have mentioned that they’re not going to expose their children to the water again,” Jim Henry, Genesee County’s environmental health supervisor, told CNN.
The findings, published online on May 21/21 in Cell, could lead to new antibiotics to fight bacterial infections. And insight into this cellular conflict could shed light on a number of other conditions in which this protein is involved, including asthma, Type 1 diabetes, primary biliary cirrhosis, and Crohn’s disease.
