Friday, November 09, 2012
Fighting bacteria with mucus
Fighting bacteria with mucus
Nov 9 2012
Nov 9 2012
Slimy layers of bacterial growth, known as biofilms, pose a significant hazard in industrial and medical settings. Once established, biofilms are very difficult to remove, and a great deal of research has gone into figuring out how to prevent and eradicate them.
Results from a recent Massachusetts Institute of Technology (MIT) study suggest a possible new source of protection against biofilm formation: polymers found in mucus. The MIT biological engineers found that these polymers, known as mucins, can trap bacteria and prevent them from clumping together on a surface, rendering them harmless.
"Mucus is a material that has developed over millions of years of evolution to manage our interactions with the microbial world. I'm sure we can find inspiration from it for new strategies to help prevent infections and bacterial colonization," says Katharina Ribbeck, the Eugene Bell Career Development Assistant Professor of Biological Engineering and senior author of the paper, which appears online in Current Biology.
Mucin coatings may help prevent biofilm formation on medical devices and could also find applications in personal hygiene: Incorporating them into products such as toothpaste or mouthwash may supplement the body's own defenses, especially in people whose natural mucus has been depleted, Ribbeck says.
Lead authors of the Current Biology paper are former MIT postdoctoral researcher Marina Caldara and Ronn Friedlander, a graduate student in the Harvard-MIT Division of Health Sciences and Technology. Other authors are Nicole Kavanaugh, an MIT graduate student in biology; Joanna Aizenberg, a professor of materials science at Harvard University; and Kevin Foster, a professor of evolutionary biology at the University of Oxford.
How to stop bacteria from teaming up
Mucus normally lines most of the wet surfaces of the body, including the respiratory and digestive tracts. "The textbook view of mucus is that it forms a barrier to infection, but it's not at all clear how it does so," Ribbeck says.
Mucus normally lines most of the wet surfaces of the body, including the respiratory and digestive tracts. "The textbook view of mucus is that it forms a barrier to infection, but it's not at all clear how it does so," Ribbeck says.
To investigate that question, Ribbeck and her colleagues observed the behavior ofPseudomonas aeruginosa bacteria in a growth medium that contained soluble purified mucins—long proteins with many sugar molecules attached.
For bacteria to effectively penetrate the mucus layer and infect the tissues below, they need to form clusters that can adhere to the tissue surface. Clumps of bacteria are much more difficult for the immune system to clear, because immune cells are specialized to attack individual bacterial cells.
"In general, you want to have bacteria around, you just don't want them to team up," Ribbeck says. "You want to them to be mixed with many other bacteria that are good for you. You don't want a single species to take over, because then they may overgrow the system."
In the new study, the researchers found that mucins block bacterial cluster formation by preventing them from adhering, which is necessary for them to clump together. When bacteria stay motile, they end up suspended in a gooey mix and can do less harm.
"The mucins have the ability to suppress virulence by keeping the cells separate. It's like keeping your kids in separate rooms, so they will stay out of trouble," Ribbeck says.
However, bacteria are sometimes able to break through this defense system and cause infections. This can be accelerated by reductions in mucus due to aging, dehydration, or chemotherapy, Ribbeck says. Or it may be that the mucus does not get replaced often enough, as happens in the mucus-clogged lungs of cystic fibrosis patients.
The finding contradicts a long-held belief that mucus is merely a sticky substance that traps more or less everything, says Gunnar C. Hansson, a professor of medical biochemistry at the University of Gothenburg in Sweden. It also "opens a new window for studies of mucins and their properties, which will help us to develop new medical therapies and biotechnological applications," says Hansson, who was not part of the research team.
'Managing microbial behavior'
One advantage of using mucins as antimicrobial coatings is that the substance disarms pathogenic bacteria without killing them. This makes it less likely that bacteria could evolve resistance to mucins, as they do to antibiotic drugs. It would also spare the beneficial bacteria that live on mucus membranes.
One advantage of using mucins as antimicrobial coatings is that the substance disarms pathogenic bacteria without killing them. This makes it less likely that bacteria could evolve resistance to mucins, as they do to antibiotic drugs. It would also spare the beneficial bacteria that live on mucus membranes.
"This is a nice mechanism where you just suppress the virulence traits without killing the bacteria," Ribbeck says. "It's nature's way of managing microbial behavioral in a way that could be useful to take advantage of."
Her laboratory is now investigating exactly how mucins prevent bacteria from losing their motility, and also how they block infection by nonmotile bacteria. Mucins seem to have wide-ranging antimicrobial properties: Ribbeck has previously shown that they can trap viruses and keep them from infecting cells, and she is now studying mucin interactions with other pathogenic organisms, such as yeasts.
Labels: antimicrobial properties, bacteria, bacterial colonization, biofilms, hygiene, immune system, mucus, polymers
# posted by Pat O'Connor @ 7:45 AM
Monday, October 22, 2007
Childhood asthma after bacterial colonization of the airway in neonates.
Childhood asthma after bacterial colonization of the airway in neonates.
N Engl J Med. 2007 Oct 11
Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen. bisgaard@copsac.dk
BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.
METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.
RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).
CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.
Copyright 2007 Massachusetts Medical Society.
N Engl J Med. 2007 Oct 11
Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen. bisgaard@copsac.dk
BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life.
METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age.
RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively).
CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.
Copyright 2007 Massachusetts Medical Society.
Labels: asthma, bacterial colonization, H. influenzae, or M. catarrhalis, S. pneumoniae
# posted by Pat O'Connor @ 10:04 AM
