Daily Archives: 26 May 2024

Intelligent skin bacteria can produce and secrete molecules to combat acne

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An international research project, spearheaded by the Translational Synthetic Biology Laboratory within the Department of Medicine and Life Sciences (MELIS) at Pompeu Fabra University, has successfully engineered a strain of Cutibacterium acnes, a common skin bacterium, to produce and secrete a molecule aimed at alleviating acne symptoms. This engineered bacterium has been tested on skin cell lines, and experiments with mice have confirmed its effectiveness. This breakthrough paves the way for synthetic biology to transform non-engineerable bacteria into agents that can manage skin conditions and other diseases through biotherapeutic methods.

The research consortium includes eminent scientists from prestigious institutions such as the Bellvitge Biomedical Research Institute (Idibell), the University of Barcelona, the Protein Technologies Facility of the Centre for Genomic Regulation, Phenocell SAS, Medizinische Hochschule Brandenburg Theodor Fontane, Lund University, and Aarhus University.

Acne is a prevalent skin ailment caused by the clogging or inflammation of pilosebaceous follicles. Manifestations range from whiteheads and blackheads to more severe forms like pustules and nodules, predominantly affecting areas such as the face, forehead, chest, upper back, and shoulders. While acne commonly appears during adolescence, it does not discriminate by age.

For more severe acne cases, traditional treatments have included antibiotics to eradicate bacteria within the follicles or isotretinoin (also known as Accutane), a vitamin A derivative that promotes the death of sebocytes—epithelial cells producing sebum. Nevertheless, these treatments can disrupt the balance of skin microbiota due to their non-selective bacterial eradication or cause severe side effects like photosensitivity and congenital disabilities.

The study, published today in Nature Biotechnology, describes how the researchers modified the genome of Cutibacterium acnes to enable the secretion of the NGAL protein, which mimics the action of isotretinoin. This protein effectively reduces sebum production by promoting the apoptosis of sebocytes.

Nastassia Knödlseder, the study’s lead author and a postdoctoral researcher at the UPF Translational Synthetic Biology Laboratory, commented on the innovation: “We have devised a topical treatment that leverages what nature already provides. By engineering a naturally occurring skin bacterium to produce therapeutic agents, we have opened the door to treating not only acne but potentially other conditions as well.”

Engineering C. acnes, previously deemed intractable for genetic modification, was overcome by improving methods for DNA delivery, enhancing the stability of DNA within the cell, and optimizing gene expression. The research team, led by Marc Güell, employed regulatory strategies to develop a biocontainment approach that eliminates concerns related to mobile genetic elements, plasmids, or antibiotic resistance markers, ensuring the safety of the synthetic bacterium for potential therapeutic applications.

The synthetic C. acnes wereld secreted NGAL in tests, regulating sebum production in cell cultures. Although initially tested in mice, whose skin differs significantly from human skin, the researchers underscore the need for alternative models that more closely resemble human skin, such as 3D skin models, to validate these findings further.

Looking ahead, Güell highlights the broader implications of their work: “Our technology platform is not limited to treating acne. It can potentially be used to engineer any bacterium to treat a wide range of diseases, from skin conditions to immune system disorders, by delivering genetic modifications that enable bacteria to sense and respond to bodily changes.”

The ongoing research under the European ‘SkinDev’ project aims to extend this technology to tackle atopic dermatitis, a chronic inflammatory skin condition prevalent among young children, by engineering C. acnes to address this and potentially other dermatological disorders.

This innovative approach to creating living therapeutics holds promise for transforming the treatment of skin conditions and other diseases, offering a new realm of possibilities in medical science. Given the safe and effective history of non-engineered C. acnes in clinical settings, the researchers remain optimistic about the potential application of these engineered microbes in human patients.

More information: Nastassia Knödlseder et al, Delivery of a sebum modulator by an engineered skin microbe in mice, Nature Biotechnology. DOI: 10.1038/s41587-023-02072-4

Journal information: Nature Biotechnology Provided by Universitat Pompeu Fabra

Medicare is covering message-based e-visits. Are older adults utilising this service?

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At the onset of the pandemic, Medicare made a pivotal move, announcing its intention to reimburse healthcare providers for the time spent managing patients’ digital messages. This landmark initiative, which primarily focused on messages involving at least five minutes of medical decision-making, marked a significant shift in healthcare policy. While these asynchronous “e-visits” conducted through secure patient portals may have received less attention compared to video and phone telehealth visits, recent research indicates that they have become a routine aspect of healthcare for some of the 30 million older Americans under traditional Medicare. Approximately 1% of this demographic engaged in patient portal messaging, prompting their healthcare providers to bill Medicare for their time. However, these billed e-visits represented only a minuscule fraction (0.05%) of all visits aimed at evaluating or managing health conditions in this population.

The study, led by researchers from the University of Michigan and published in Health Affairs Scholar, revealed that nearly half of the billed e-visits involved primary care providers, primarily assisting patients with hypertension or diabetes. Following a surge at the pandemic’s onset, the rate of billed e-visits in traditional Medicare stabilised consistently until the end of 2022. Nonetheless, it’s important to note that a considerable volume of patient portal messages circulate daily without generating a bill, such as requests for prescription refills or updates on the patient’s well-being, which were not part of the study due to the unavailability of data without billing information.

The transformation in care delivery, particularly the increasing use of patient portal messaging, has significantly impacted the workflow of primary care clinicians. Dr Terrence Liu, the study’s lead author and a National Clinician Scholar at U-M’s Institute for Healthcare Policy and Innovation, emphasises the need for a deeper understanding of how such care modalities can be optimally utilised by both patients and providers. He highlights the potential implications on clinic operations, provider burnout, and patient outcomes. For instance, while e-visits offer a convenient tool for chronic disease management, they also pose challenges for clinicians, especially those managing large patient panels, as even a few lengthy e-visits can consume significant time not accounted for in their schedules.

To effectively handle the influx of patient portal messages, some clinics have implemented triage systems, assigning dedicated staff members to screen and allocate messages to appropriate responders. This strategic approach helps preserve physician and advanced-practice provider time for addressing inquiries that require their expertise the most. However, variations exist in how different clinics triage portal messages, underscoring the need for standardised protocols to ensure consistency and efficiency across healthcare settings. This discussion on managing patient portal messages presents an intriguing area for further research and development in healthcare delivery.

Despite the potential benefits of e-visits, concerns linger regarding the financial implications for patients. At the same time, Medicare covers e-visits and insurance coverage for such services varies, leading some providers to hesitate to bill portal exchanges to avoid passing costs onto patients. Dr Liu underscores the importance of further research to assess the impact of e-visits on overall healthcare utilisation and explore the content and outcomes of these interactions, particularly regarding chronic disease management. Additionally, it’s crucial to evaluate whether adopting patient portal e-visits exacerbates healthcare disparities, potentially widening the gap among patients with differential access to and proficiency in communication technologies.

More information: Terrence Liu et al, National trends in billing patient portal messages as e-visit services in traditional Medicare, Health Affairs Scholar. DOI: 10.1093/haschl/qxae040

Journal information: Health Affairs Scholar Provided by University of Michigan Health