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Lanthanide Nanohybrids Show Promise In Treating Pulmonary Biofilm Infections

Bacterial biofilm infections are among the leading causes of morbidity and mortality among patients with cystic fibrosis or those with weakened immune systems. Treatment for biofilm infections usually entails intensive antibiotic therapy. There is an urgent need for well-designed agents to achieve in vivo diagnosis and precise anti-biofilm therapy without bacterial resistance. Unfortunately, no effective agent has been designed to perform these tasks adequately.

In a study published in ACS Nano, a research group led by Prof. Chen Xueyuan from Fujian Institute of Research on the Structure of Matter (FJIRSM) of the Chinese Academy of Sciences (CAS) achieved noninvasive phototheranostics in a mice model with Pseudomonas aeruginosa biofilm-induced pulmonary infection.

Researchers fabricated novel sunflower-like structured alginate lyase (Aly)-NaNdF4 nanohybrids through an enrichment-encapsulating strategy, which showed an excellent photothermal conversion efficiency, the second near-infrared (NIR-II) luminescence emission, as well as an ideal particle size for delivery to the lung.

When Aly-NaNdF4 nanohybrids were located in biofilm-infected lungs, pH-responsive Aly molecules were released from the mesopores of nanohybrids due to the acidic environment, thus resulting in targeted degradation of biofilms. At the same time, the nanohybrids showed a strong positive charge that enhanced their adhesion to bacteria, which prolonged the stay of nanohybrids in the lung.

By monitoring the luminescence intensity of nanohybrids in the lungs, the extent of infection and therapeutic effectiveness could be evaluated in real time.

Researchers showed that the nanohybrids achieved a strong biofilm eradication by utilizing the synergistic effect of Aly and photothermal therapy. The viability of P. Aeruginosa in vitro was reduced by 5.3 log10, achieving a disinfecting effect. The number of bacteria in the lungs of the treated mice was reduced by 94%.

Notably, the nanohybrids were mainly metabolized in the liver and spleen, and could be basically cleared from the body on day eight after intravenous injection, effectively avoiding the potential long-term toxicity of nanomaterials.

This study is an exploration of biofilm-targeted theranostic nanoagents toward internal organ infections based on luminescent lanthanide nanohybrids, which is of great significance to facilitate precision medicine research and clinical practice in the treatment of biofilm-associated infections.

More information: Zhuo Li et al, Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection, ACS Nano (2024). DOI: 10.1021/acsnano.4c00777

Citation: Lanthanide nanohybrids show promise in treating pulmonary biofilm infections (2024, June 11) retrieved 11 June 2024 from https://phys.Org/news/2024-06-lanthanide-nanohybrids-pulmonary-biofilm-infections.Html

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An Anti-inflammatory Curbs Spread Of Fungi Causing Serious Blood Infections

A team of UC Davis Health researchers discovered that a common anti-inflammatory drug, mesalamine, can replace the work of good bacteria in fighting the nasty fungus Candida albicans in the gut.

C. Albicans, or candida, is known to cause yeast infections. In some cases, it develops into invasive candidiasis, a potentially fatal infection occurring mostly in patients with compromised immunity.

The researchers found that this fungus can't grow without an oxygen supply. Their study in mice showed that the drug can maintain a low oxygen (hypoxia) environment that prevents fungal bloom in the gut.

Their study appears today in Cell Host & Microbe.

Antibiotic use may lead to fungal bloom in the gut

The team studied how C. Albicans colonizes the gut. The fungus, best known for causing vaginal yeast infections, is usually treated with a topical or oral antifungal without serious side effects. It also harmlessly lives in the gut of around 60% of people.

Yet, when the body's immunity goes down due to cancer or chemotherapy, the fungus may grow beyond the colon and spread throughout the body. In such cases, the patient develops invasive candidiasis.

"Invasive candidiasis is a potentially deadly infection with a mortality rate of around 50%. That's even with the best available treatment," explained the study's lead author Andreas Bäumler. Bäumler is a distinguished professor in the Department of Medical Microbiology and Immunology.

Patients with leukemia and other blood cancers may need to take antibiotics. This use may cause an imbalance in the gut's microbial community. It reduces Clostridia, a group of bacteria that promotes resistance to fungi colonization in the gut. With less Clostridia, C. Albicans grows and colonizes in the tract.

"A bloom of C. Albicansin the gut during antibiotic therapy is the most common cause of candidemia in people treated for blood cancers," Bäumler explained. Candidemia is the presence of fungi or yeast in the blood.

Bäumler and his team wanted to understand the factors involved in antibiotic-induced colonization of C. Albicans in the gut.

Candida loves simple sugars and oxygen

They first colonized germ-free mice with Candida to see what the fungus consumed to bloom. They realized that Candida really liked simple sugars, similar to those found in high-sugar diets. Then, they tested its growth in a petri dish. They placed Candida with simple sugars in an aerobic (with oxygen) setting, and the fungi bloomed.

"A healthy gut has low oxygen. So, we repeated the test in a hypoxia setting," Bäumler said. The fungi didn't grow despite the presence of sugars. This meant oxygen is a necessary condition for Candida growth.

The role of probiotics in preventing fungal growth

The team did a series of experiments that showed antibiotic use reduced Clostridiain the gut. Giving mice probiotics, such as Clostridia, prevented C. Albicans from growing in the gut. Yet, probiotics can be killed by antibiotics and cancer therapy. For this reason, probiotics would not help patients with leukemia or other blood cancers.

"Probiotics are often not safe in patients at the highest risk for invasive candidiasis," Bäumler said. "Finding a therapy that can function like probiotics but can endure the impact of cancer treatment and antibiotics was important."

Anti-inflammatory drugs as faux-biotics

The team explored 5-aminosalicylic acid (5-ASA) as a safer way to control C. Albicansin the gut. 5-ASA, also known as mesalamine, is an anti-inflammatory drug. It is used to treat inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis.

The team tested 5-ASA in mice treated with antibiotics. They found that the drug could replace the work of probiotics by preventing oxygen in the colon and C. Albicans from expanding in the gut.

"Limiting oxygen in the gut by replacing the function of good bacteria could be a strategy for reducing invasive candidiasis," Bäumler said. "Our study opens a totally new treatment option for fatal fungal infections, especially for patients with cancer. After all, fungi cannot become resistant against hypoxia."

The team proposed the term "faux-biotics" to refer to products, such as 5-ASA, that mimic the function of probiotics like Clostridia.

The first coauthors of the study are Hannah Savage, Derek Bays and Connor Tiffany. The other co-authors are Mariela Gonzalez, Eli Bejarano, Thaynara Carvalho, Zheng Luo, Hugo Masson, Henry Nguyen, Renato Santos, Krystle Reagan and George Thompson of UC Davis.

2 New Fungal Infections Emerge In US, What To Know

Experts at New York City-based NYU Langone Health are warning healthcare providers to be aware of two highly contagious fungal infections causing rashes, according to a June 5 news release shared with Becker's.

NYU Langone Health researchers honed in on two separate studies to draw these conclusions. One focused on the spread of a sexually transmitted fungal infection, tinea, found to be caused by Trichophyton mentagrophytes type VII and the other focused on Trichophyton indotineae.

Both fungi species can lead to ringworm rashes, jock itch and athlete's foot, but there are changes in how some of these rashes are now presenting, according to the research, published June 5 in JAMA Dermatology. 

"Healthcare providers should be aware that Trichophyton mentagrophytes type VII is the latest in a group of severe skin infections to have now reached the United States,"  Avrom Caplan, MD, study lead author and dermatologist at NYU Grossman School of Medicine said in the release.

Until now, the fungal infection has not been identified in the U.S., but has been increasingly spotted across Europe in recent months, with 13 cases confirmed in France in 2023. It's usually diagnosed in men who have male sexual partners.

While cases of Trichophyton mentagrophytes type VII are challenging to treat and can take several weeks or months to clear up, so far, those infections have been responding to terbinafine as a treatment, according to NYU Langone researchers. 

However, infections with Trichophyton indotineae have become harder to treat, a separate study, also by NYU Langone, published May 15 in JAMA Dermatology, found. 

Trichophyton indotineae infections, while newer, have been reported in the U.S. Before. But, instances of infections have spread globally since, and it often is a strain that does resist typical terbinafine treatments. Some success has been reported in patients treated for the fungal infection with another antifungal called itraconazole. Although, it is a drug that can have uncomfortable side effects if used long term for treatment.

"These findings offer new insight into how some of the fungal skin infections spreading from South Asia can evade our go-to therapies," Dr. Caplan said in the release. "Beyond learning to recognize their misleading signs, physicians will need to ensure their treatment addresses each patient's quality-of-life needs."

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