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Sugars in mother's milk a new class of antibacterials
"This is the first example of generalized, antimicrobial activity on the part of the carbohydrates in human milk. One of the remarkable properties of these compounds is that they are clearly non-toxic, unlike most antibiotics."
Steven D. Townsend PhD, Assistant Professor of Chemistry, Department of Chemistry, Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, USA, and director of the study.
The growing problem of bacterial resistance to antibiotics is the motivation for the research. The Center for Disease Control and Prevention estimates approximately 23,000 deaths annually from antibiotic resistance. The proportions of Group B Streptococcus (group B strep, GBS) with in vitro resistance to clindamycin or erythromycin have increased over the past 20 years. "We started to look for different methods to defeat infectious bacteria, turning to one - Group B Strep - in particular. We wondered whether its common host, pregnant women, produce compounds that can either weaken or kill strep, a leading cause of infections in newborns worldwide," explains Townsend. Centers for Disease Control and Prevention, Fast Facts.
Townsend and his colleagues turned their attention to milk sugars, which are considerably more difficult to study. "For most of the last century, biochemists argued that proteins are more important and sugars are an afterthought — even though there's no data to support this," Townsend adds. "Far less is known about the function of sugars and, as a trained glycoprotein chemist, I wanted to explore their role."
Researchers collected and ranked human milk carbohydrates, also called oligosaccharides, using mass spectrometry to identify thousands of large biomolecules. Researchers then added these biomolecules to strep cultures. Not only did some of these oligosaccharides kill the bacteria directly — some also physically broke down the biofilms that bacteria form for protection.
In a small pilot study, Townsend's lab set up five tests on strep. In one, breast milk sugars killed almost an entire colony. In a second, the sugars appeared moderately effective. In the remaining three, there was a lower level of activity. As a follow-up, they tested more than two dozen samples. Two broke down the bacterial biofilms and killed all bacteria, four broke down biofilms but did not kill the bacteria, and two killed the bacteria without breaking down the biofilms.
"Our results show that these sugars have a one-two punch. First, they sensitize the target bacteria and then they kill them. Biologist sometimes call this 'synthetic lethality.' There is a major push to develop new antimicrobial drugs with this capability."
Steven D. Townsend PhD
By dosing strep cultures with a mixture of breast milk sugars and antimicrobial peptides from human saliva, researchers found breast milks' ability to break down biofilms also enhances the effectiveness of other antimicrobial agents in mother's milk, including two of the six "ESKAPE" pathogens that are leading causes of hospital infections worldwide.
Townsend is collaborating with colleagues in Vanderbilt's Mass Spectrometry Research Center to identify specific carbohydrate molecules responsible for the antibacterial effects discovered.
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillbirth, and neonatal sepsis. Recently, breastfeeding has been thought to represent a potential mode of GBS transmission from mother to newborn, which might increase the risk for late-onset sepsis. Little is known, however, about the molecular components of breast milk that may support or prevent GBS colonization. In this study, we examine how human milk oligosaccharides (HMOs) affect the pathogenesis of GBS. HMOs from discrete donor samples were isolated and profiled by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Growth and biofilm assays show that HMOs from mothers of specific milk groups can modulate the growth and biofilm formation of GBS. High-resolution field-emission gun scanning electron microscopy (SEM) and confocal laser scanning microscopy confirmed the quantitative biofilm assays and demonstrated cell arrangement perturbations in bacterial cultures treated with specific oligosaccharides. These findings demonstrate that HMOs affect the growth and cell biology of GBS. Finally, this study provides the first example of HMOs functioning as antibiofilm agents against GBS.
Keywords: antibiofilm; antimicrobial; bacteriostatic; GBS; Group B Streptococcus; HMO; human milk oligosaccharides
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Breast milk's blend of proteins, fats and sugars somehow helps
protect babies against bacterial infections.
Image credit: Public domain