The Human Milk Glycome as a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities

Abstract

Each year over 3 million people die from infectious diseases with most of these deaths being poor and young children who live in low- and middle-income countries. Infectious diseases emerge for a multitude of reasons. On the social front, reasons include a breakdown of public health standards, international travel, and immigration (for financial, civil, and social reasons). At the molecular level, the modern rise of infectious diseases is tied to the juxtaposition of drug-resistant pathogens and a lack of new antimicrobials. The consequence is the possibility that humankind will return to the preantibiotic era wherein millions of people will perish from what should be trivial illnesses. Given the stakes, it is imperative that the chemistry community take leadership in delivering new antibiotic leads for clinical development. We believe this can happen through innovation in two areas. First is the development of novel chemical scaffolds to treat infections caused by multidrug-resistant pathogens. The second area, which is not exclusive to the first, is the generation of antibiotics that do not cause collateral damage to the host or the host’s microbiome. Both can be enabled through advances in chemical synthesis. It is with this general philosophy in mind that we hypothesized human milk oligosaccharides (HMOs) could serve as novel chemical scaffolds for antibacterial development. We provide herein a personal account of our laboratory’s progress toward the goal of using HMOs as a defense against infectious diseases.

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

“…As such, we feel that HMOs possessing narrow-spectrum antibacterial activity represent particularly exciting tools to combat infectious disease. 54 …”

Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents

“…It contains lysozyme, an enzyme which destroys the structural peptidoglycan layer surrounding bacterial cells and which is recognized to be a key component of innate immunity (81). It also contains oligosaccharides which can inhibit bacterial growth and biofilm formation and sensitize them to antibiotics via membrane permeabilization (82)(83)(84)(85). Further, it contains the protein lactoferrin, which sequesters vital iron away from pathogenic bacteria.…”

Mehr als 200 gute Gründe für das Stillen

“…Neben dem großen Gebiet der Babynahrung werden HMO auch für den Einsatz auf anderen Feldern untersucht. Es besteht die Möglichkeit, HMO als neue chemische Bausteine für die Entwicklung von dringend erforderlichen Antimikrobiotika einzusetzen [ sowie darin (57): Ackerman 2017].…”

“…Um diese Forschungen zu ermöglichen, werden Chemiker, Biologen und Ingenieure weiter Wege finden, komplexe HMO‐Verbindungen aber auch potente analoge Substanzen [ darin (46): Ackerman 2017) zu identifizieren und in sowohl kleinen als auch industriell verfügbaren Mengen zu synthetisieren.…”