Before 2020 and the COVID-19 pandemic, concern among infectious disease specialists was rising about Candida auris, an emerging fungal pathogen that is often drug-resistant and difficult to eradicate from hospitals.
Many people know Candida can cause mouth or vaginal infections and diaper rashes. According to the CDC, Candida also can cause invasive infections in the bloodstream, particularly in hospital or nursing home patients with weakened immune systems. About 30 percent of patients with an invasive Candida infection die – and C. auris is just one particularly hardy variety.
Emory Antibiotic Resistance Center director David Weiss and colleagues have identified a combination of existing antifungal drugs (micafungin and amphotericin B) with enhanced activity against C. auris when used together. The results – in vitro only, so far — were published in a letter to The Lancet Microbe. Postdoctoral fellow Siddharth Jaggavarapu was the first author. Weiss reports his team continues to investigate combination approaches against C. auris.
The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.
Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.
Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella. Bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics.These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.
In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars. Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized based on a past study that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.
The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens. The authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.
When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.
In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.
C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.
At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.
Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more
A new paper in PNAS from Emory scientists highlights a neat example of bacterial evolution and adaptation related to sexually transmitted infections. Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, sometimes appears in the news because of cases on college campuses or other outbreaks.
Genetic changes make this clade look more like relatives that are known to cause gonorrhea. Some good news is that these guys are less likely to cause meningitis because they have lost their outer capsule. They have also gained enzymes that help them live in low oxygen.
The DNA analysis helps doctors track the spread of this type of bacteria and anticipate which vaccines might be protective against it. Thankfully, no alarming antibiotic resistance markers are present (yet) and currently available vaccines may be helpful. Full press release here, and information about meningococcal disease from the CDC here.
This looks like a well-worn path in bacterial evolution, since N. gonorrhoeae is thought to have evolved from N. meningitidis and there are recent independent examples of N. meningitidis adapting to the urogenital environment.
If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.
A diagnostic test used by hospitals says a recently isolated strain of bacteria is susceptible to the “last resort” antibiotic colistin. But the strain actually ignores treatment with colistin, causing lethal infections in animals.
Through heteroresistance, a genetically identical subpopulation of antibiotic-resistant bacteria can lurk within a crowd of antibiotic-susceptible bacteria. The phenomenon could be causing unexplained treatment failures in the clinic and highlights the need for more sensitive diagnostic tests, researchers say.
“Heteroresistance has been observed previously and its clinical relevance debated,” Weiss says. “We were able to show that it makes a difference in an animal model of infection, and is likely to contribute to antibiotic treatment failures in humans.”
Weiss is director of the Emory Antibiotic Resistance Center and associate professor of medicine (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. His laboratory is based at Yerkes National Primate Research Center. The co-first authors of the paper are graduate students Victor Band and Emily Crispell.
Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.
Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.
One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.
As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making itâ€™s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle.Read more
The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.
While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more
A term we heard a bunch at the Emory Microbiome Symposium in November was â€œmetagenomicsâ€. Time for an explainer, with some help from Emory geneticist Tim Read.
Nature Reviews Microbiology defines metagenomics as â€œgenomic analysis of microbial DNA that is extracted directly from communities in environmental samples.â€
This technology â€” genomics on a huge scale â€” enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.
Read notes that the term specifically refers to â€œshotgunâ€ sequencing of environmental DNA.
The bacteria and other microbes that live within the human body are thought to influence not only digestive health, but metabolic and autoimmune diseases as well, possibly even psychiatric and neurodevelopmental disorders. The field is being propelled by next-generation sequencing technology, and Nature had to publish an editorial guarding against hype (a major theme: correlation is not causation).
At Emory, investigators from several departments are involved in microbiome-related work, and the number is expanding, and assembling a comprehensive list is becoming more difficult. Researchers interested in the topic are planning Emory’s first microbiome symposium in November, organized by Jennifer Mulle (read her intriguing review on autism spectrum disorders and the microbiome).
Microbial genomics expert Tim Read, infectious diseases specialist Colleen Kraft and intestinal pathologist Andrew Neish have formed an Emory microbiome interest group with a listserv and seminars.
Microbiome symposium sponsors: ACTSI, Hercules Exposome Center, Emory University School of Medicine, Omega Biotek, CFDE, Ubiome.Read more