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Microbiology

Resistant bacteria are a global problem. Now researchers may have found the solution

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Staphylococcus aureus. You may have had it in connection with a wound infection. In most cases, it will pass without treatment, while severe cases may require antibiotics, which kills the bacteria. This is the case for the majority of the population. In fact, many of us — though we feel perfectly fine — carry staphylococci in the nose, a good, moist environment in which the bacteria thrive.

However, more and more staphylococci are becoming resistant to antibiotics (also known as multi resistant staphylococcus aureus or MRSA), and these infections can be difficult to treat.

“Antibiotics resistance is an increasing problem, especially on a global scale. And when you have this relatively simple infection which suddenly cannot be treated with antibiotics, the situation can turn serious, sometimes life-threatening,” says Professor Niels Ødum from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen.

Therefore, all over the world, a lot of resources are being invested in fighting antibiotics resistance in staphylococcus aureus infections, and a new study among skin lymphoma patients has produced positive results. A new substance called endolysins has proven capable of killing both resistant and non-resistant staphylococcus aureus — without the need for antibiotics. But we will get back to that.

The discovery is good news to patients with a weak immune system to whom a staphylococcus aureus infection can be serious and, at worst, fatal. But it also adds to the knowledge we have of other forms of treatment.

“To people who are severely ill with e.g. skin lymphoma, staphylococci can be a huge, sometimes insoluble problem, as many are infected with a type of staphylococcus aureus that is resistant to antibiotics,” says Niels Ødum and adds:

“That is why we are careful not to give antibiotics to everyone, because we do not want to have to deal with more resistant bacteria. Therefore, it is important that we find new ways of treating — and not the least to prevent — these infections.”

New substance may be the answer

In some patients, a staphylococcus aureus will cause the cancer to worsen. And even though antibiotics appear to work in some cases, it is not without its problems.

“We can tell that giving high doses of antibiotics to patients with serious infections causes their health, skin and cancer symptoms to improve. But once we stop giving them antibiotics, the symptoms and staphylococci quickly return. Patients experience many adverse effects, and some risk getting resistant bacteria,” says Niels Ødum.

Therefore, treating staphylococcus aureus can be tricky. At worst, cancer patients may die of an infection which doctors are unable to treat.

And this is where endolysins enter the scene, as this new substance may be part of the solution to antibiotics resistance like MRSA.

“This particular endolysin is a brand new, artificially produced enzyme that has been improved several times and designed as a new drug,” explains Postdoc Emil Pallesen, who is first author of the study. He adds:

“The great thing about this enzyme is that it has been designed to penetrate the wall of staphylococcus aureus. This enables it to target and kill the harmful staphylococcus and leave harmless skin bacteria unharmed.”

And that is what made the researchers decide to test the new substance; they expected it to be able to kill both resistant and non-resistant staphylococcus bacteria.

“We have been testing the substance on skin samples from patients, and it does appear to kill staphylococcus aureus from patients. Endolysins do not care whether the bacterium is resistant to antibiotics or not, because it does not work in the same way as antibiotics,” says Niels Ødum and adds:

“The really good news is that our lab tests have showed that endolysins do not just eradicate staphylococcus aureus; they also inhibit their ability to promote cancer growth.”

  • Emil M.H. Pallesen, Maria Gluud, Chella K. Vadivel, Terkild B. Buus, Bob de Rooij, Ziao Zeng, Sana Ahmad, Andreas Willerslev-Olsen, Christian Röhrig, Maria R. Kamstrup, Lene Bay, Lise Lindahl, Thorbjørn Krejsgaard, Carsten Geisler, Charlotte M. Bonefeld, Lars Iversen, Anders Woetmann, Sergei B. Koralov, Thomas Bjarnsholt, Johan Frieling, Mathias Schmelcher, Niels Ødum. Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma. Journal of Investigative Dermatology, 2023; DOI: 10.1016/j.jid.2023.01.039

    • University of Copenhagen – The Faculty of Health and Medical Sciences
    Microbiology

    Study examines bacteria living in and on mosquitoes

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    Avoiding mosquitoes to protect against bites is always a good idea. But a new North Carolina State University study shows that the bacteria-ridden exteriors of mosquitoes may be another reason to arm yourself with a swatter.

    The first-of-its-kind study, published in PLOS ONE, examined both the exterior surface and interior microbiome of mosquitoes found in homes in Africa’s Cote d’Ivoire — the Ivory Coast.

    “When you’re exposed to mosquitoes, you worry about blood feeding,” said R. Michael Roe, William Neal Reynolds Distinguished Professor of Entomology at NC State and co-corresponding author of the study. “Our hypothesis is that mosquitoes can physically transfer bacteria by landing on you or by defecating on household surfaces, like flies do.

    “They may not, but no one has studied it before.”

    Research collaborators at the Centre Suisse de Recherches Scientifiques collected 79 adult female Anopheles coluzzii mosquitoes from homes in a rice-producing province in Cote d’Ivoire. The mosquitoes were sent to NC State for analysis of the microbiome inside and on external body surfaces.

    Some of the findings were surprising.

    “We found greater bacterial diversity internally than externally, which didn’t match what has been found with blow flies, for example,” said Loganathan Ponnusamy, an NC State principal research scholar in entomology and co-corresponding author of the paper.

    “At the same time, we found lots of external bacterial differences between homes, but not much difference internally between homes, which makes sense. Much of what is found internally relates to nectar or honey consumed as mosquitoes forage outdoors.”

    The researchers also found — for the first time in the academic literature — fructobacillus, which is generally found in nectar sources like flowers and beehives, pointing to mosquitoes visiting those plants or nectar sources, said Kaiying Chen, an NC State postdoctoral researcher and first author of the paper.

    Perhaps more ominously, the researchers also found large amounts of Staphylococcus and two variants of Rickettsia. The genus of these bacteria are associated with human and animal diseases.

    “This is another risk,” Roe said. “Mosquitoes carry bacteria externally and internally and come into your home, possibly transferring pathogenic bacteria.”

    The researchers hope to continue the work by exposing mosquitoes to a bacteria that would never be found on human skin and seeing whether the bacteria transfers to an artificial membrane. They then could perform the same test on human arms.

    NC State Ph.D. researchers Chouaïbou S. Mouhamadou and Jean M. Deguenon co-authored the paper, as did Behi Kouadio Fodjo, Gba Christabelle Sadia and France Paraudie Kouadio Affoue from the Centre Suisse de Recherches Scientifiques, Abidjan, Cote d’Ivoire, Africa. Funding was provided by a grant from the Department of the Army under a Deployed Warfighter Protection (DWFP) Program Grant W911QY1910003.

    Story Source:

    Materials provided by North Carolina State University. Original written by Mick Kulikowski. Note: Content may be edited for style and length.

    Journal Reference:

  • Kaiying Chen, Loganathan Ponnusamy, Chouaïbou S. Mouhamadou, Behi Kouadio Fodjo, Gba Christabelle Sadia, France Paraudie Kouadio Affoue, Jean M. Deguenon, R. Michael Roe. Internal and external microbiota of home-caught Anopheles coluzzii (Diptera: Culicidae) from Côte d’Ivoire, Africa: Mosquitoes are filthy. PLOS ONE, 2022; 17 (12): e0278912 DOI: 10.1371/journal.pone.0278912

    • North Carolina State University
    Microbiology

    Gut microbes disturbed by COVID-19 infection, especially with antibiotics

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    In an intensive look at the effects of the virus causing COVID-19 on patients’ microbiome — the collection of microorganisms that live in and on the human body — Rutgers scientists found that acute infection disrupts a healthy balance between good and bad microbes in the gut, especially with antibiotic treatment.

    The work may lead to the development of probiotic supplements to redress any gut imbalances in future patients, the scientists said.

    Reporting in the scientific journal Molecular Biomedicine, researchers described the first results of an ongoing study examining the microbiome of patients and volunteers at Robert Wood Johnson University Hospital in New Brunswick. The study, which began in May 2020, the early days of the pandemic, was designed to zero in on the microbiome because many COVID-19 sufferers complained of gastrointestinal issues — both during the acute phases of their illness and while recuperating.

    “We wanted to gain a deeper understanding by looking at specimens that would give us an indication about the state of the gut microbiome in people,” said Martin Blaser, the Henry Rutgers Chair of the Human Microbiome at Rutgers University, director of the Center for Advanced Biotechnology and Medicine (CABM) at Rutgers and an author on the study. “What we found was that, while there were differences between people who had COVID-19 and those who were not ill, the biggest difference from others was seen in those who had been administered antibiotics.”

    Early in the pandemic, before the introduction of vaccines and other antiviral remedies, it was a common practice to treat COVID-19 patients with a round of antibiotics to attempt to target possible secondary infections, said Blaser, who also is a professor of medicine and pathology and laboratory medicine at Rutgers Robert Wood Johnson Medical School.

    Humans carry large and diverse populations of microbes, Blaser said. These microorganisms live in the gastrointestinal tract, on the skin and in other organs, with the largest population in the colon. Scientists such as Blaser have shown over recent decades that the microbiome plays a pivotal role in human health, interacting with metabolism, the immune system and the central nervous system.

    The microbiome has many different functions. “One is to protect the human body against invading pathogens, whether they’re bacteria or viruses or fungi,” Blaser said. “That goes deep into evolution, maybe a billion years of evolution.”

    Medical problems often arise when the balance between beneficial and pathogenic microbes in a person’s microbiome is thrown off, a condition known as dysbiosis.

    The scientists studied microbiomes by measuring populations of microorganisms in stool samples taken from 60 subjects. The study group consisted of 20 COVID-19 patients, 20 healthy donors and 20 COVID-19-recovered subjects. They found major differences in the population numbers of 55 different species of bacteria when comparing the microbiomes of infected patients with the healthy and recovered patients.

    The Rutgers scientists plan to continue to test and track the microbiomes of patients in the study to ascertain the long-term effect on individual microbiomes from COVID-19.

    “Further investigation of patients will enhance understanding of the role of the gut microbiome in COVID-19 disease progression and recovery,” Blaser said. “These findings may help identify microbial targets and probiotic supplements for improving COVID-19 treatment.”

    Other Rutgers scientists on the study included Yue Sandra Yin, the study’s first author and a research teaching specialist at CABM; Veenat Parmar, program administrator of the Rutgers Microbiome Program; Vinod Rustgi, Distinguished Professor of Medicine, clinical director of hepatology and director of the Center for Liver Diseases and Liver Masses at Robert Wood Johnson Medical School; as well as Carlos Minacapelli, Carolyn Catalano, Abhishek Bhurwal and Kapil Gupta, all of the Division of Gastroenterology and Hepatology and the Center for Liver Diseases and Masses at the Robert Wood Johnson School of Medicine.

    The study was supported by Danone and by the National Institutes of Health (National Institute of Allergy and Infectious Diseases).

    Story Source:

    Materials provided by Rutgers University. Original written by Kitta MacPherson. Note: Content may be edited for style and length.

    Journal Reference:

  • Yue Sandra Yin, Carlos D. Minacapelli, Veenat Parmar, Carolyn C. Catalano, Abhishek Bhurwal, Kapil Gupta, Vinod K. Rustgi, Martin J. Blaser. Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery. Molecular Biomedicine, 2022; 3 (1) DOI: 10.1186/s43556-022-00103-1

    • Rutgers University