Archive : Fall 2006


A TOPOLOGY OF BIOFILMS:
Bacteria, as many as 600 cohabitating species // Autoinducers, the chemicals through which the beasties communicate // A polymeric matrix, the defense force that makes these gooey infections nearly impossible to subdue.

Slime and the City [page 3]


Given evidence that cholera might form biofilms in humans, Watnick speculates that biofilms might fuel cholera’s rapid spread of infection by concentrating its toxin, which invades the cells lining human intestines and prompts ion channels in those cells to open wide. Fluid pours out into the intestines, causing victims to die of dehydration. The cholera germ is shed into the environment in feces, and may be picked up by other humans or returned to seawater to form another biofilm.

Other, less exotic human pathogens also form biofilms. Staphylococcus epidermidis, which lives as a harmless commensal, or fellow traveler, on human skin, shows an unnerving capacity to form low-grade—but stubborn and dangerous—biofilm infections on artificial implants. According to Paul Fey, associate professor at the University of Nebraska Medical Center in Omaha, S. epidermidis appears to be able to bind to any surgical material—stainless steel, zirconium, ultra-high-molecular-weight polyethylene—though when it comes to infection, not all S. epidermidis strains are created equal.

The strains of this normally harmless germ that cause infection all seem to contain a special packet of genes, or an operon, that codes for the formation of S. epidermidis biofilms, while cultures grown from S. epidermidis that has been taken from human skin generally lack it. Though no one is sure where the biofilm-forming genes came from, bacterial strains with the operon have clearly evolved to thrive in the hospital environment. In fact, Fey believes many S. epidermidis germs infecting catheters worldwide may be members of a single clone.

In patients these staph biofilms (with the operon) produce chronic infections that are almost impossible to cure. This is because biofilms have several ways to fight off attacks by antibiotics and antiseptics, says Philip Stewart, director of the Center for Biofilm Engineering at Montana State University in Bozeman. For example, the usually potent antiseptic chlorine bleach (which has been tried against biofilms that form in pipes and cooling systems) loses its killing power as it filters through a biofilm’s dense network of organic matter. In the human body, white blood cells normally kill bacterial invaders with tiny bursts of oxygen in the form of superoxide, peroxide and hydrochloric acid. But this mechanism too seems powerless against biofilms. It may deactivate surface layers, but it can’t get to all of the cells embedded in the matrix.

Antibiotics, effective against free-moving planktonic bacteria, also seem unable to destroy those that reside in biofilms. It appears that the exopolysaccharide matrix does not block the drug from reaching the bacterial cells, so there must be some other mechanism by which the biofilm neutralizes the antibiotic’s effect.

Part of the problem, says Stewart, is that antibiotics typically target only growing, metabolically active cells—for example, by preventing the cells from reproducing. But many of the bacterial inhabitants of biofilms exist in a dormant or inactive state—and thus are unaffected by an onslaught of antibiotics. As a result, even if a drug kills almost all of the bacteria in a biofilm, a few dormant cells may live to infect another day, re-forming a pernicious biofilm on an implant.

With conventional therapies thwarted, doctors are left with only one radical choice: to cut out the infected implant. For a patient with an infected artificial hip, that means having the entire implant removed, with a spacer left behind that must stay in place until the infection has been completely eradicated. Only then can a new implant be installed. This extreme approach is a throwback to the days before antibiotics, when surgeons had to cut out pockets of infection, and adds up to a lot of surgery—with all of the risks and pain that come with it.


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