A Tale of Two Toxins: the mechanisms of cell death in Clostridium difficile infections

When someone is admitted to a hospital for an illness, the hope is that medical care and treatment will help them them feel better. However, nosocomial infections—infections acquired in a health-care setting—are becoming more prevalent and are associated with an increased mortality rate worldwide. This is largely due to the misuse of antibiotics, allowing some bacteria to become resistant. Furthermore, when an antibiotic wipes out the “good” bacteria that comprise the human microbiome, it leaves a patient vulnerable to opportunistic infections that take advantage of disruptions to the gut microbiota.

One such bacteria, Clostridium difficile, is of growing concern world-wide since it is resistant to many different antibiotics. When a patient is treated with an antibiotic, C. difficile can thrive in the intestinal tract without other bacteria populating the gut. C. difficile infection is the leading cause of antibiotic-associated diarrhea. While symptoms can be mild, aggressive infection can lead to pseudomembranous colitis—a severe inflammation of the colon which can be life-threatening.

C. difficile causes disease by releasing two large toxins, TcdA and TcdB. Understanding the role these toxins play in colonic disease is important for treatment strategies. However, most published research data only report the effects of the toxins independently. A 2016 study demonstrated a method of comparing the toxins side-by-side using the same time points and cell assays to investigate the role each toxin plays in the cell death that leads to disease of the colon. Continue reading

Culturing the Unculturable

Culturing bacteria is't always this easy.

Culturing bacteria is’t always this easy.

It is estimated that all the bacterial species so far described represent only a tiny fraction of the total. The rest remain unknown to science because they are “unculturable” in standard (or known) laboratory media. Given that many antibiotics were first isolated from environmental bacteria, it seems likely that these as yet unknown organisms could also be a rich source of potential new drug candidates. The desperate need for new strategies to combat multi-drug resistant infections gives impetus to studies investigating how we can culture some of these “unculturable” bacteria and uncover their potential as a source of much-needed new treatments.  Continue reading

Hope for Treatment of Carbapenem-Resistant Bacteria

Structure of the antibiotic meropenem

Structure of the antibiotic meropenem

Last month brought some hopeful news on the subject of antibiotic resistance. A paper published in Nature on June 26 described the isolation of a fungal compound that restored the antibiotic sensitivity of carbapenem-resistant enterobacteria. An editorial accompanying the paper took encouragement from the article–considering it a sign that the well of potential sources of new antimicrobial agents, and agents that inhibit resistance mechanisms, is not yet dry:

But the reservoir of natural products with the potential to act as antibacterial drugs has not yet been exhausted. In contrast to general thinking by drug companies, screening for such products may well still have a bright future” Nature News and Views: “Antibiotic resistance: To the rescue of old drugs” Meziane-Cherif & Courvalin, Nature 510, 477–478.

The emergence of bacteria that are resistant to antibiotics has been an object lesson in the relentlessness of natural selection; the moment a new antibiotic is developed and introduced, the countdown to the emergence of resistance begins. The race to keep the one step ahead of emerging resistance mechanisms has been going on since antibiotics were first introduced.

The history of the development of penicillin and related antibiotics is both an illustration of the ingenuity of scientists and of the never-ending nature of this battle with emerging resistance. The Nature paper is the latest installment in that story. Continue reading

Antibiotics and Honey–An Old Solution for a New Problem

Antibiotic DiskThis month saw the publication of a UK Department of Health report on the growing problem of antimicrobial resistance, which included the shocking recommendation that antimicrobial resistance be added to the UK government list of threats to national security alongside terrorism and pandemic flu. In this report, Professor Dame Sally Davies, Chief Medical Officer for the UK, focused on the increasing problem of multidrug resistant organisms–raising the profile of an important issue that many scientists and health-care professionals have warned us about before. A March 12 Nature editorial welcomed the recommendations as a sign that policy makers in the UK are taking the threat of antimicrobial resistance seriously and are prepared to take more steps to address the problem of multidrug-resistant organisms. Continue reading

Copper Containing Surfaces and Their Potential for Reducing the Spread of Infection and Antibiotic Resistant Gene Transfer

As a scientist and a jewelry artist, there are not that many occasions when my two passions overlap. As a geneticist, I find the evolution and spread of antibiotic resistant microbes to be fascinating in a “this is really cool and utterly terrifying” sort of way. As a jewelry artist, I love experimenting with new and different metals. Some of my current favorites are stainless steel, copper and bronze, which is an alloy of copper and tin. So you might be able to imagine my excitement when I came across an article in mBio discussing the public health implications of horizontal gene transfer (HGT) of antibiotic resistance genes on clinical and public touch surfaces made from copper alloys compared to those made of stainless steel (1).

Stainless steel: The unexpected, gene-transferring truth

Polishing stainless steelStainless steel is often used in clinical and public settings as work surfaces as well as other surfaces that are touched and cleaned often. Stainless steel is used in these applications for many of the same reasons I like it for jewelry: it is strong, resilient, relatively inexpensive, stain- and corrosion-resistant and will weather regular cleaning/exposure to moisture well. There is something about a gleaming stainless steel work surface that looks, well, sterile. But is it? Continue reading

The Search for New Antibiotics: Looking for Achilles’ Heel (Again)

Some of the first available doses of penicillin were used to treat allied soldiers wounded on D-Day. It was the end of one war, but just the beginning of another–one that has gone on for a long time. The story of the development of antibiotics, and the emergence of resistant bacteria, followed by the renewed search for new antibiotics, seems neverending. As soon as a new antibiotic is discovered, it seems only a matter of time before a resistance mechanism emerges, and remaining one step ahead of the bugs can seem like a relentless challenge. Continue reading