Effects of Biocides on antibiotic resistance

4. How can bacteria become resistant to biocides or antibiotics?

• 4.1 How can bacteria become resistant to biocides?
• 4.2 How can bacteria become resistant to antibiotics?
• 4.3 Which resistance mechanisms are common to both biocides and antibiotics?

4.1 How can bacteria become resistant to biocides?

Bacteria become resistant to biocide exposure when they are able to limit their internal concentration of active biocide to harmless levels. Bacteria can do this by a number of methods and may combine several.

For instance, some bacteria become resistant by changing the structure of their cell envelope so that it lets in smaller amounts of biocides. This is particularly the case of bacteria that grow as biofilms attached to surfaces. The outer layers of biofilms are considerably less permeable than those of free bacteria, and this could lead them to be much less easily affected by biocides and antibiotics.

Some bacteria become more tolerant to biocides by activating a system that “pumps out” toxic compounds generally termed efflux pump. This reduces the efficacy of biocides.

Some bacteria use enzymes to cause chemical changes in biocides and to degrade them so that they are less effective, but it is not clear whether this mechanism is relevant for the high concentrations of biocides used in practice.Some bacteria use enzymes to cause chemical changes in biocides and to degrade them so that they are less effective, but it is not clear whether this mechanism is relevant for the high concentrations of biocides used in practice.

Bacteria can modify the parts of their structure that biocides attach to and attack. However, there are many different sites that biocides can target so modifying one of these does not have a large effect on increased resistance.

Bacteria that could previously be controlled by a biocide can develop resistance by acquiring resistance genes and this is a serious cause for concern. In some cases, exposure to a low biocide concentration leads to genetic changes that make the bacteria resistant to several unrelated compounds, but the mechanism for this is unknown.

Recent studies have demonstrated that some biocides are able to activate several genes that are involved in the control of resistance mechanisms affecting the activity of biocides and antibiotics.

Sometimes bacteria become resistant once they reach sufficiently high numbers. Bacteria secrete certain “signal” molecules that other bacteria can detect. Once bacteria detect enough of these from neighbouring bacteria, the whole colony activates specific genetic cascades involved in the formation of biofilms. This mechanism is involved in the development of resistance to biocides and antibiotics but more research is needed in this field. More...

4.2 How can bacteria become resistant to antibiotics?

Antibiotics work either by altering the bacterial envelope or by interfering with important physiological processes inside the bacteria as well as with their growth.

Table 10: Mechanisms of action of antibiotics

Bacteria may be “insusceptible” or intrinsically resistant to an antibiotic because they have no sites that the molecule can attack, because the envelope does not let the antibiotic in, because some efflux pumps expel the antibiotic, or because the bacteria produce enzymes that destroy it.

An increasing and ongoing concern are bacterial strains that become resistant by mutation, by changing their gene expression or by transfer of resistance genes from other bacteria. The transfer of genes can take place in different ways but usually involves genes that can move between different parts of the genome. Some of these acquired genes enable the bacterium to destroy the antibiotic or to expel it and others change the parts of the bacteria that antibiotics attack. There are three possible mechanisms:

1. Bacteria can make their membrane less permeable to the antibiotic or “pump out” any antibiotic from the cell before it starts to act by producing an efflux pump.
2. Bacteria can attack the antibiotic (alter the structure) and make it ineffective by producing detoxifying enzymes.
3. Bacteria can protect or modify the parts of their structure that antibiotics attack (target mutation) or can produce decoys that antibiotics attack instead of the real target sites.

“Multi-drug resistant bacteria” that become simultaneously resistant to different classes of antibiotics are a cause for serious concern in hospitals, where they are commonly found. They mainly act by pumping out any compounds harmful to them so that their concentration inside the bacteria becomes harmless in addition to other resistance mechanisms including target mutation or detoxifying enzymes.

Once resistant bacteria emerge, using antibiotics can help resistant strains thrive by killing other strains so that bacteria with resistance genes can grow and reproduce without competition from other strains. These bacteria can also transfer their resistance genes to other bacteria of similar or different species. More...

4.3 Which resistance mechanisms are common to both biocides and antibiotics?

There are many similarities in the ways that biocides and antibiotics penetrate bacteria and work. Both diffuse into bacteria, they can modify or destroy the bacterial membrane, i.e. the layer that encloses the bacterium, and can disrupt key steps in bacterial chemical reactions. Therefore, some bacterial mechanisms of defence are effective against both antibiotics and biocides such as the decrease of membrane permeability that reduce the uptake of active molecules, or the production of efflux pumps that expel antibiotic and biocide molecules.

Genes that confer resistance to antibiotics can also be involved in biocide resistance such as efflux pump genes, so bacteria that acquire resistance genes sometimes become resistant to both types of antimicrobials at the same time. In other cases, genes that confer resistance to different antimicrobial products (such as beta-lactams and quaternary ammonium products) are very close to each other in a same genetic element (plasmid, transposon, etc) transferable from one bacterium to another. As a result, when this genetic element passes from one bacteria to another, both types of resistance genes (to antibiotics and to biocides) are transmitted together.

In yet other cases, exposing bacteria to some biocides can activate the genes responsible for resistance against both biocides and antibiotics.

This raises concerns over the indiscriminate and often inappropriate use of biocides in situations where they are unnecessary, because it can contribute to the development of resistance mechanisms. This is especially important in cases where potentially harmful bacteria, such as those found in hospitals, are exposed to biocides. More...