Disassembling bacteria’s protective walls

A multidisciplinary team of GlycoNet investigators is making strides towards taking down drug-resistant bacteria

By Alexandria Daum

A bacterial or fungal infection is difficult enough to treat, but when these infections form protective biofilms, it makes them even more stubborn. Now, the solution being explored by GlycoNet scientists is to prevent the biofilm from forming in the first place.

“Bacteria and fungi can produce a force field or matrix around themselves,” says Dr. Lynne Howell, lead investigator of the project and a researcher at The Hospital for Sick Children
 in Toronto. This force field – the biofilm – is a protective barrier composed of proteins, DNA and sugar polymers that makes bacteria or fungi 1,000 times more tolerant of antibiotics.

The team, made up of eight network investigators, is studying four different sugar polymers found in microbial biofilms, with the aim of influencing polymer composition and biofilm production. For these polymers, the addition or removal of acetate is critical for the virulence of the bacteria. A fifth polymer being studied is crucial for the structural integrity
 of the bacteria and in this case, the addition
of acetate allows resistance to host defence mechanisms.

“The general concept is that if you can prevent the removal or addition of acetate, then you have a means of modulating the biofilm that’s formed and reducing the virulence of the bacteria, or removing their resistance to innate immune response,” says Howell.

By disrupting the biofilm’s production, the overall goal is to make a bacterial or fungal infection more treatable.

“We would use these inhibitors in conjunction with traditional antimicrobials. This could prevent bacteria from forming biofilms in
the first place, which will make conventional antibiotics much more effective,” says Howell. “We would have the ability to target a very large number of different pathogens through the various polymers that we’re hitting.”

This approach could be particularly effective in chronic bacterial infections, such as cystic fibrosis. About 80 per cent of chronic bacterial infections are thought to produce biofilms.

“We need alternative ways of treating chronic infections,” says Howell. “It’s increasingly appreciated that targeting free-swimming bacteria or fungi is not relevant to the types of infections in which the bacteria or fungi are now embedded in a biofilm.”

In addition, Howell and her team suspect that this approach may help slow antibiotic resistance, which has been identified by the Centers for Disease Control and Prevention in the United States as one of the most pressing health issues of our time.

“If you’re not putting a selective pressure on the bacteria to be killed, then resistance to the compounds we’re developing should develop more slowly.”