Sugar additive — trehalose — may supercharge C. difficile

Amina Khan of the LA Times reports two bacterial strains that have plagued hospitals around the country may have been at least partly fueled by a sugar additive in our food products, scientists say.

Trehalose, a sugar that is added to a wide range of food products, could have allowed certain strains of Clostridium difficile to become far more virulent than they were before, a new study finds.

The results, described in the journal Nature, highlight the unintended consequences of introducing otherwise harmless additives to the food supply.

  1. difficile is a nasty bacterium — infection can result in severe diarrhea and death — and numbers among the most prevalent hospital-acquired infections in the United States. According to the Centers for Disease Control and Preventionnearly half a million peoplewere sickened by the bug in 2011. Some 29,000 of those patients died within 30 days of being diagnosed with C. difficile, and about 15,000 of those deaths were directly linked to the infection.

The disease wasn’t always such a scourge of the sick and hospitalized, and scientists have long been trying to figure out why certain strains have become so successful in recent years. The misuse and overuse of antibiotics has long been thought to be responsible for the rise of many kinds of antibiotic-resistant “superbugs.”

To probe the mystery, a team of scientists led out of Baylor College of Medicine in Texas examined two particularly successful lineages of C. difficile, RT027 and RT078, examining what kind of carbon-rich molecules they ate. Both types, they noticed, seemed very good at using low concentrations of the sugar trehalose as a sole carbon source.

The researchers analyzed the genomes of both RT027 and RT078. While both had RNA sequences that allowed each type to take advantage of trehalose in low doses, they did so in very different ways.

  1. difficile bacteria have genes that can break trehalose into glucose (a simpler, more useful sugar) and its derivatives. But a special protein called TreR blocks the microbes from metabolizing trehalose unless the concentration of trehalose in the environment is very high.

In RT027, the TreR protein is modified in a way that lowers the bar, allowing the bacteria to metabolize trehalose even in quite low concentrations.

RT078, however, is using a different mechanism to do the same thing, having picked up four genes that are used in taking up and metabolizing trehalose. (Just one of them, it turns out, was responsible for its powered-up ability to grow in small amounts of trehalose.)

Dietary trehalose enhances virulence of epidemic clostridium difficile

Nature, 03 January 2018, J. Collins, C. Robinson, H. Danhof, C. W. KnetschH. C. van LeeuwenT. D. LawleyJ. M. AuchtungR. A. Britton, doi:10.1038/nature25178

\Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose.

RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose.

We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.


Could Clostridium difficile be transferred by meat?

Spores of toxigenic Clostridium difficile and spores of food-poisoning strains of Clostridium perfringens show a similar prevalence in meats. Spores of both species are heat resistant and can survive cooking of foods. C. perfringens is a major cause of foodborne illness; studies are needed to determine whether C. difficile transmission by a similar route is a cause of infection.

C.difficile A possible route for foodborne transmission of Clostridium difficile?

Foodborne Pathogens and Disease [ahead of print]

Lund Barbara M. and Peck Michael W.

I’m missing something here: NJ school closed due to staff with C. difficile?

According to NBC 10, Perth Amboy’s William McGinnis Middle School is closed for cleaning and sanitizing as a staff member was found to have C. difficile.

Perth Amboy’s William McGinnis Middle School remains closed while it undergoes an extensive cleaning after an adult who works there was diagnosed with a germ that causes infectious diarrhea.LP_img_ClosedSchool

The school was closed as a precaution on Friday after the woman was sent home on Thursday. The district says she has an intestinal bacillus known as clostridium difficile.

The district did not release her name or say what her job is.

The district says it has hired a company to completely disinfect the school and classes are scheduled to resume on Thursday.

Closing a school for C. difficile is a new one to me.

Maybe they mean norovirus, I dunno.

In a 2009 review of C. difficile infections, Rupnik, Wilcox and Gerding suggest that the pathogen is out there (environmentally and in food) but risk factors for acquiring the pathogen include the use of antibiotics and hospital stays. Not going to a school where someone has the bug.

Hospitalization is a risk because it brings together multiple major [C. difficile infection]  CDI risks, including exposure to antibiotics, a spore-contaminated environment, inadequate hand hygiene by health care workers and a highly susceptible elderly population of patients

Possible community sources for CDI include soil, water, pets, animals used for food, meats and vegetables. There is no conclusive evidence that C. difficile contamination of food has led to clinical CDI in humans.

I wonder if they will be using hydrogen peroxide to disinfect (it’s not too common outside of healthcare).

Whole genome sequencing reveals potential spread of Clostridium difficile between humans and farm animals in the Netherlands, 2002 to 2011

Farm animals are a potential reservoir for human Clostridium difficile infection (CDI), particularly PCR ribotype 078 which is frequently found in animals and humans. Here, whole genome single-nucleotide polymorphism (SNP) analysis was used to study the evolutionary relatedness of C. difficile 078 isolated from humans and animals on Dutch pig farms.

UQ.piggeryAll sequenced genomes were surveyed for potential antimicrobial resistance determinants and linked to an antimicrobial resistance phenotype. We sequenced the whole genome of 65 C. difficile 078 isolates collected between 2002 and 2011 from pigs (n = 19), asymptomatic farmers (n = 15) and hospitalised patients (n = 31) in the Netherlands. The collection included 12 pairs of human and pig isolates from 2011 collected at 12 different pig farms. A mutation rate of 1.1 SNPs per genome per year was determined for C. difficile 078. Importantly, we demonstrate that farmers and pigs were colonised with identical (no SNP differences) and nearly identical (less than two SNP differences) C. difficile clones.

Identical tetracycline and streptomycin resistance determinants were present in human and animal C. difficile 078 isolates. Our observation that farmers and pigs share identical C. difficile strains suggests transmission between these populations, although we cannot exclude the possibility of transmission from a common environmental source.

Euro Surveill. 2014;19(45):pii=20954

Knetsch CW, Connor TR, Mutreja A, van Dorp SM, Sanders IM, Browne HP, Harris D, Lipman L, Keessen EC, Corver J, Kuijper EJ, Lawley TD