Antimicrobial activity of “useless” or “toxic” molecules:

The past year saw expansion of a very important paradigm shift: a growing number of human compounds previously regarded as “useless” or “toxic” are actually potent antimicrobial peptides (peptides that form part of the innate immune response TOWARDS microbes in tissue + blood). Compounds shown to possess this antimicrobial activity include amlyoid beta (Alzheimer’s), alpha-synuclein (Parkinson’s) and even prions. Here are two important 2018 studies on the topic:

Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection.

Lead author: Robert Moir, MassGeneral Institute for Neurodegenerative Disease

In 2016 Moir and team showed that amyloid beta, a protein that accumulates in the Alzheimer’s brain, has potent antimicrobial activity against fungal and bacterial pathogens. In this 2018 study, the team found that amyloid beta also protects against herpesviruses commonly found in the brain. In fact, the team showed that amyloid beta can bind to proteins on herpesvirus membranes and clump into fibrils that entrap the virus and prevent it from entering human cells.

Antimicrobial and Antibiofilm Activity of Human Milk Oligosaccharides against Streptococcus agalactiae, Staphylococcus aureus, and Acinetobacter baumannii

Lead author: Steven Townsend, Vanderbilt University

The study adds to previous work showing that breast milk proteins called Human Milk Oligosaccharides (HMOs) have potent antimicrobial activity. This particular analysis found that HMOs possessed both antimicrobial and antibiofilm activity against strains of methicillin-resistant S. aureus and A. baumanniiThe absence of these HMOs (and other antimicrobial molecules) in infant formula may help explain why formula-feeding is associated with a number of negative health outcomes.

Infants Are Exposed to Human Milk Oligosaccharides Already in utero

Lead author: Lars Bode University of California, San Diego

The team detected HMOs in samples of amniotic fluid removed from women during and after pregnancy. The findings suggest that HMOs may additionally help control pathogens + organisms capable of persisting in the womb.

Prion-like Domains in Eukaryotic Viruses

Lead author: Victor Tetz, Human Microbiology Institute, New York

PrD enrichment in the proteomes of different viral orders (Tetz et al)

The team used a computational algorithm to show that viral prion-like proteins (PrDs) can be found in a range of human viral pathogens. They also revealed probable functional associations between PrDs and different steps of viral replication + interaction with host cells. Since prions have been shown to have antimicrobial activity, I wonder if some PrDs could play a role in viral defense? It’s also worth noting bacteria have been shown to produce amyloid (a similar pattern).

Paper highlight: “The predictive approach employed in this study revealed for the first time a large set of putative PrDs in numerous proteins of the emerging human viral pathogens, including those associated with persistent viral infections, oncogenic processes, hemorrhagic fevers, and others.”

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