- Microbial biofilm is a sticky
substance formed by microorganisms to colonize body surfaces; it prevents
antibiotic penetration and protects microbes from host immunity.
- New enzyme technique that
prevents formation as well as destroys formed biofilm improves treatment
efficacy by exposing the organisms to antibiotics and host defense.
enzymatic mechanism to tackle microbial biofilm has been developed by a research
team led by the Research Institute of the McGill University Health Centre
(RI-MUHC) and The Hospital for Sick Children.
The results of the study, published in Proceedings of the
National Academy of Sciences
(PNAS) may lead to the development of fresh treatment strategies
to manage several infections.
biofilm is a slimy sticky substance secreted
by microorganisms such as bacteria and fungi to colonize and establish
themselves on the surface of tissues, as well as on devices introduced into the
such as catheters, tubes, and implants such as heart valves, and
‘Tackling microbial biofilms increases the efficacy of treatment by improving penetration of antimicrobial agents and exposing the organisms to host defense mechanisms.’
biofilm forms a sticky coating on the
surface of tissues or implants and protects the underlying organisms
being acted on by host immune mechanisms or antimicrobial agents.
the biofilm acts both as a physical and
and poses a major challenge for successful eradication of
hospital acquired infections such as urinary tract infections
, lung infections
) and bloodstream infections.
associated infections are associated with high rates of mortality
and cause numerous deaths across North America each year.
does the Microorganism Make the Biofilm?
The biofilm consists of a matrix of sugar
molecules such as galactosaminogalactan and Pel
secreted by opportunistic pathogens such
as Pseudomonas spp and Aspergillus spp which are associated with recurrent
respiratory infections in persons with chronic lung diseases.
The research team studied the ways by which these two organisms
formed the biofilm during the course of the infection.
The microbes used certain enzymes (glycoside hydrolases) to cut the released sugar
molecule in places and reattach it at some other site
in an effort to remodel
the sticky matrix.
"Microbes use these enzymes to move
sugar molecules around and cut them into pieces in order to build and remodel
the biofilm matrix," says Dr. Sheppard, who is also a professor in the
departments of Medicine and Microbiology and Immunology at McGill University.
Own Tool To Break Down The Biofilm
This study is the result of a four-year
successful joint venture between Dr. Sheppard's team and scientists in the
laboratory of Dr. P. Lynne Howell, senior scientist in the Molecular Medicine
program at SickKids.
a cue from their observations, the team of scientists developed a
technique to use the very same enzymes used by the bacteria to remodel the
sugar armor, but to prevent formation and cause degradation of the biofilm
and expose the organism to antibiotics and host defense in patients.
"We were able to use the microbe's own tools against
them to attack and destroy the sugar molecules that hold the biofilm
together," says the study's co-principal investigator, Dr. Don Sheppard,
director of the Division of Infectious Diseases at the MUHC and scientist from
the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC.
interesting observation was that the enzymes found in the bacteria were
used against fungal biofilm, it successfully degraded the fungal biofilm as
well, indicating cross-species
attempts in combating biofilms were only partially successful in that they
prevented biofilm formation. The authors claim that their study is the
first successful attempt at breaking down the formed biofilm which was
verified in mouse models.
"We made these enzymes into a
biofilm destroying machine that we can use outside the microbe where the sugar
molecules are found," explains co-first study author Brendan Snarr, a PhD
student in Dr. Sheppard's laboratory. "These enzymes chew away all of the
sugar molecules in their path and don't stop until the matrix is destroyed."
of The Study
The outcome of the study indicates that glycoside hydrolases enzymes can
break down the sugar matrix
of the biofilm of diverse microbes and could be used as possible therapeutic
agents to increase antibiotic efficacy and to weaken the virulence of the
Says Dr Sheppard, "Over 70 percent
of hospital-acquired infections are actually associated with biofilms and we
simply lack tools to treat them!"
In conclusion, this could indeed be a golden opportunity and the lead scientists hope
to commercialize it in the not too distant future.
- Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity - (http://biorxiv.org/content/early/2017/03/04/113696)