The Path of Least Resistance

Microbes that cause us health problems and considerable expense often live in a biofilm. Inside a biofilm microbes become highly resistant to antibiotics and other methods of eradication – solving this issue is of paramount importance to the healthcare sector…

Microbes are often thought of as free floating, singular, life forms, devoid of senses and very much alone in life. The vast majority of bacteria actually exist in biofilms; which in the simplest definition is the point at which a free-floating bacterium attaches to a surface and starts multiplying. Within biofilms, micro-organisms relay signals that create parts of the biofilm – structures such as water channels and the slime it is protected by. These highly specialised and complex biological systems have been identified in 3.2-billion-year-old rocks in Pilbara Craton, Australia. This early appearance in nature exhibits how integral biofilm production is to microbial organisms. It is not exaggerating to suggest that the biofilm mode of life is the most successful biological system on the planet.

The matrix of slime that the bacteria surround themselves in is composed of carbohydrates, fats, proteins, DNA and other small compounds. This slime protects bacteria from the environment, attaches them to surfaces, allows digestion inside the biofilm and connects cells to one another. It is not surprising that the sticky matrix can constitute up to 90% of biofilm dry mass – it is vitally important to the microbes that live in a biofilm. The components of this slime vary depending on the microbes that are present. Currently our knowledge of the slime matrix is poor; its complexity and the difficulty of measuring substances have caused this.

A fungal biofilm living on a surface.

Biofilms are highly resistant to the immune system, viral attack, UV radiation, physical forces, water loss, biocides, and antibiotics. Increased resistance to the drugs used in hospitals is due to many factors: 1) restricted penetration of the drugs through the slime, 2) slow growth of bacteria (most antibiotics work on microbes that are multiplying), 3) resistant microbes (super bugs), and 4) altered chemical microenvironments. The bacteria within a biofilm can exhibit extremely complex and coordinated behaviour. Cell signalling and quorum sensing, a way of bacterial communication, allows the microbes to sense and respond to the local environment, thereby increasing survival chances. High levels of resistance are therefore related to three major factors – the slime “wall”, bacterial behaviour, and the communities within the matrix. Complexity means the biofilm is extraordinarily resistant to severe conditions.

A biofilm is a major obstacle - defended by its slime "wall".

Bacterial biofilms often form on living tissues (like a sinus cavity or open wound) or on the inert surfaces of medical devices (like pacemakers or replacement hips). A common example of this would be the plaque that is forming on your teeth this very minute – a biofilm that is only kept in check by the mechanical action of a toothbrush. Of the bacterial infections treated by physicians, some 60% are thought to be biofilm related. Conventional medicine treats planktonic bacteria well but traditional therapy can have little effect on biofilms; it is not surprising that after billions of years of adaptation that the biofilm manner of life is resistant to many deleterious agents. Typically chronic diseases arise from biofilm infections; they remain hard to treat, costing health services time and money whilst reducing patient quality of life.

So as mentioned, biofilms cause a variety of infectious diseases and are resistant to conventional healthcare therapy – to solve this problem we need novel ideas. One such promising idea actually hopes to turn the biofilm microbes against themselves. It makes sense that the microbes that form biofilms should have a means of escape, either for spreading to a new location or running from environmental problems. The release of cells requires modification of the slime, usually by enzymes produced from the microbes living inside the biofilm. These enzymes break apart the carbohydrates or proteins that form the sticky, impenetrable slime – thus dissolving it and thereby releasing the microbes from within. Recently scientists have begun to take these enzymes and use them against biofilms, biofilm warfare of the 21st century kind – this appears to be the most promising avenue in the treatment of biofilm infections.

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