Disinfectants Can Make Bacteria Resistant To Treatment

Society for General Microbiology

Chemicals used in the environment to kill bacteria could be making them stronger, according to a paper published in the October issue of the journal Microbiology. Low levels of these chemicals, called biocides, can make the potentially lethal bacterium Staphylococcus aureus remove toxic chemicals from the [bacterial] cell even more efficiently, potentially making it resistant to being killed by some antibiotics.


Biocides are used in disinfectants and antiseptics to kill microbes. They are commonly used in cleaning hospitals and home environments, sterilizing medical equipment and decontaminating skin before surgery. At the correct strength, biocides kill bacteria and other microbes. However, if lower levels are used the bacteria can survive and become resistant to treatment.

"Bacteria like Staphylococcus aureus make proteins that pump many different toxic chemicals out of the [bacterial] cell to interfere with their antibacterial effects," said Dr Glenn Kaatz from the Department of Veterans Affairs Medical Center in Detroit, USA. "These efflux pumps can remove antibiotics from the cell and have been shown to make bacteria resistant to those drugs. We wanted to find out if exposure to biocides could also make bacteria resistant to being killed by the action of efflux pumps."

The researchers exposed S. aureus taken from the blood of patients to low concentrations of several biocides and dyes, which are also used frequently in hospitals. They looked at the effect of exposure on the bacteria and found that mutants that make more efflux pumps than normal were produced.

"We found that exposure to low concentrations of a variety of biocides and dyes resulted in the appearance of resistant mutants," said Dr Kaatz. "The number of efflux pumps in the bacteria increased. Because the efflux pumps can also rid the cell of some antibiotics, pathogenic bacteria with more pumps are a threat to patients as they could be more resistant to treatment."

If bacteria that live in protected environments are exposed to biocides repeatedly, for example during cleaning, they can build up resistance to disinfectants and antibiotics. Such bacteria have been shown to contribute to hospital-acquired infections.

"Scientists are trying to develop inhibitors of efflux pumps. Effective inhibitors would reduce the likelihood of additional resistance mechanisms emerging in bacteria," said Dr Kaatz. "Unfortunately, inhibitors evaluated to date do not work on a wide range of pathogens so they are not ideal to prevent resistance."

"Careful use of antibiotics and the use of biocides that are not known to be recognised by efflux pumps may reduce the frequency at which resistant strains are found," said Dr Kaatz. "Alternatively, the combination of a pump inhibitor with an antimicrobial agent or biocide will reduce the emergence of such strains and their clinical impact."

Contact: Lucy Goodchild
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Society for General Microbiology
 

Adapted from materials provided by Society for General Microbiology, via EurekAlert!, a service of AAAS.

 

Disinfectants Can Make Bacteria Resistant To Treatment:  Created on October 7th, 2008.  Last Modified on October 7th, 2008

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· 10 years ago

The Kaatz paper [1] should be considered in conjunction with an earlier paper by Hassan [2]. These 2 papers refer strictly to the development of resistance to biocides by Gram-positive bacteria. The Hassan paper shows that, in addition to mutations in plasma membrane-bound drug transporters that lead to antibiotic resistance, resistance to certain common small-molecule biocides such as quaternary ammonium compounds, biguanidines, and diamidines can be developed in these transporters.

Both papers refer to the effects of sub-lethal concentrations of biocides. The drug resistance being referred to for non-antibiotic biocides in Gram-positive bacteria arises from mutations in the drug transporter proteins that decrease the uptake of a biocide or facilitate the more rapid efflux of the biocide molecules from the cell cytoplasm.

The mechanisms leading to the development of small molecule biocide resistance appear to be similar to the mechanism leading to the development of antibiotic resistance in Gram-positive bacteria: Namely, gene transfer between bacterial cells that confers drug resistance via bacterial conjugation.

There has been much recent interest in these drug transporters of Gram-positive bacteria because if a way were found to design molecules that could inhibit the drug efflux transporters in a wide variety of bacterial specie, the efficacy of known biocides could be greatly increased. So far, no such inhibitors with practical uses have been designed.

The Kaatz paper has shown is that for S. aureus moderate increases in the minimum inhibitory concentrations (MICs) for the common biocide benzalkonium chloride (BAC) can be observed after populations of the bacterium are exposed to sub-lethal doses of the biocide.
This is a very interesting paper provided that the results and conclusions reported in it are not over-interpreted. First, it only refers to Gram-positive species—in fact, only one species. Second, it does refer to treatment of the bacterium with sub-lethal concentrations of BAC. Resistance does not develop in bacteria exposed to sufficient doses of biocide. Third, the increases in MICs were relatively small.

The cautionary tale that the Kaatz paper relates is that biocides used in disinfection to remove Gram-positive microbials should be of sufficient concentration to kill them quickly and, if at all possible, biocides that kill by straight chemical reactions on the bacteria without the necessity of the biocide being taken up into the cell cytoplasm should be used.

References

[1] Huet, A. A., J. L. Raygada, et al. (2008). Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes. Microbiology 154(Pt 10): 3144-53.

[2] Hassan, K. A., R. A. Skurray, et al. (2007). Active export proteins mediating drug resistance in staphylococci. J Mol Microbiol Biotechnol 12(3-4): 180-96.

October 8th, 2008 | 2:07pm Reply

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The objective of the Society for General Microbiology (SGM) is to advance the art and science of microbiology. SGM provides a common meeting ground for scientists working in research and in fields with applications in microbiology, including medicine, veterinary medicine, pharmaceuticals, numerous industries, agriculture, food, the environment and education. The majority of members are employees of universities, research institutes, health services, government agencies and small to multinational companies.

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