Toothpaste ingredient linked to antibiotic resistance


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"A common ingredient of soap and toothpaste could be causing antibiotic resistance and fuelling the spread of superbugs," the Mail Online reports.


This news follows the results of a study that looked at whether there could be a common reason why some gut bacteria have resistance to both the quinolone class of antibiotics and the chemical triclosan.


Triclosan has antibacterial properties and is found in a wide range of products, ranging from soap to cleaning products to children's toys. It's also found in some brands of toothpaste as it protects against gum disease. Quinolones are antibiotics often used to treat digestive infections such as E. coli and salmonella.


This study found E. coli and salmonella bacteria with mutations to a particular gene (gyrA) had some degree of resistance to both triclosan and quinolones. The mechanism of resistance was slightly different for the two substances.


The researchers also found that when certain mutant E. coli strains were exposed to low levels of triclosan, they became more dominant (grew more) than other bacteria, but only if they were already present.


Reassuringly, triclosan exposure didn't lead to new mutations developing in previously normal E. coli bacteria. But this doesn't rule out the possibility that triclosan could contribute to bacterial resistance in other ways.


In an accompanying press release, the researchers point out that traditional cleaning methods, such as soap, water and bleach, can be just as effective as antimicrobial branded products – and they don't contribute to the increasing threat of antibiotic resistance


Where did the story come from?


The study was carried out by researchers from the Institute of Microbiology and Infection at the University of Birmingham, and the Quadram Institute and John Innes Centre at Norwich Research Park.



It was supported by training grants received by individual researchers, and published in the peer-reviewed Journal of Antimicrobial Chemotherapy.


The Mail Online's coverage was accurate, and included some useful background information on how the US Food and Drug Agency has recently banned triclosan from personal cleaning products such as soap and body gel because of concerns about safety and antibiotic resistance.


The chemical is still used in some brands of toothpaste, both in the US and the UK, and has not been banned in the UK.


What kind of research was this?


This laboratory study aimed to see whether there could be a common link between bacterial resistance to quinolone antibiotics and resistance to triclosan.


Antimicrobial resistance is a global public health problem. As bacteria develop resistance to increasingly stronger antibiotics, we're reaching a point where this is overtaking the rate at which new antibiotics can be developed.


A world without effective antibiotics would see a return to a situation where routine surgeries become far riskier, and some conditions become untreatable.


Triclosan is a biocide – a chemical that can destroy micro-organisms. It's found in many household and cosmetic products like antiseptic soaps, body washes and toothpastes.


Quinolones are a group of commonly used antibiotics, including drugs like ciprofloxacin. Drugs in this group are used to treat a wide range of digestive tract infections, such as salmonella, as well as various respiratory, skin and urinary tract infections.


Quinolones mainly destroy bacteria by targeting a particular bacterial enzyme called DNA gyrase. The gyrA gene codes for this enzyme, and bacteria with mutations to this gene are resistant to quinolones because the antibiotics can no longer bind to this site.


A recent study has shown that salmonella bacteria with gyrA mutations were also less susceptible to triclosan.


The researchers aimed to investigate what mechanism could be causing the bacteria to become more tolerant to quinolone after being exposed to triclosan (a process known as "cross resistance"). 


What did the research involve?


This study involved normal (wild type) strains of E. coli and salmonella bacteria, as well as those with gyrA gene mutations.


Researchers looked at how well the bacteria were able to grow in the presence of quinolones and triclosan, and the minimum concentration of each drug or chemical needed to prevent bacterial growth.


They used laboratory methods to introduce new gyrA mutations and see how drug resistance differed by specific mutation.


As triclosan isn't known to directly target DNA gyrase in the same way as quinolones, they investigated the mechanism by which gyrA mutations could influence triclosan resistance.


The researchers finally tested the possibility that a suboptimal concentration of triclosan – below the level normally needed to stop bacterial growth – might support the growth of bacteria with gyrA mutations.


What were the basic results?


The research showed that both E. coli and salmonella bacteria with gyrA mutations were resistant to some degree to both the quinolone ciprofloxacin and to triclosan.


Eight times the ciprofloxacin concentration was needed to prevent bacterial growth, and four times the concentration of triclosan.


The researchers showed that there was some difference in the susceptibility of E. coli and salmonella to ciprofloxacin depending on the specific mutation the bacteria carried.


They confirmed that, as expected, triclosan doesn't directly target DNA gyrase. They found gyrA mutations in E. coli bacteria increased activity of the bacteria's main "stress response pathways", and this was how they were resistant to triclosan.


Stress response pathways is a term used to describe molecular "defences" that protect against environmental stresses or "threats".


The mechanism was slightly different for salmonella. In the "competitive fitness" tests, researchers found that exposure to low concentrations of triclosan led to E. coli bacteria with a specific gyrA mutation (Asp87Gly) becoming more dominant than other bacteria. The same effect wasn't seen with salmonella.


However, a promising finding was that previous exposure to low-concentration triclosan didn't lead to new quinolone-resistant mutations developing among the wild type bacteria. 


How did the researchers interpret the results?


The researchers concluded that, "Our data suggest gyrA mutants are less susceptible to triclosan due to up-regulation of stress responses. The impact of the gyrA mutation differs between E. coli and Salmonella."


They went on to say that, "The impacts of the gyrA mutation beyond quinolone resistance have implications for the fitness and selection of gyrA mutants in the presence of non-quinolone antimicrobials." 


Conclusion


This study mainly explored why bacterial resistance could be common for both quinolone antibiotics like ciprofloxacin and the antibacterial triclosan.


It confirmed previous findings that one cause seems to be bacteria developing mutations in the gyrA gene.


In the case of quinolones, the mutation alters the enzyme that they normally bind to. Triclosan resistance is largely because the already-mutant bacteria have boosted stress response pathways, or molecular defences.


The main finding of this research was that small triclosan concentrations led to resistant E. coli bacteria becoming the more dominant strains more likely to survive and reproduce.


This may cause concern that low concentrations in everyday products like toothpastes and body washes could lead to the development of antibiotic-resistant bacteria.


But this study didn't find direct evidence for this. Certain mutant E. coli strains did become more dominant, but only if they were already present.


Importantly, triclosan exposure didn't lead to new mutations developing in previously normal E. coli bacteria. This means that this research didn't demonstrate that triclosan causes the development of drug-resistant bacteria.


Nevertheless, there could be other mechanisms that cause resistance, aside from gyrA gene mutations. And triclosan exposure could also have an effect on the effectiveness of other antimicrobials.


This study will undoubtedly be an important contribution to the body of evidence on triclosan.


In 2016, the US Food and Drug Administration (FDA) banned the sale of antiseptic washes containing triclosan (and other ingredients) because of concerns that exposure could carry risks to human health, including being a possible cause of cancer, as well as potentially contributing to antimicrobial resistance.


The EU is also phasing out its use in domestic products, and European agencies are monitoring evidence on its safety and effectiveness.


Triclosan is still used in some brands of toothpaste, as it's thought to prevent gum disease.


Links To The Headlines

Common disinfectant found in soap and toothpaste could be causing antibiotic resistance. Mail Online, June 4 2017


Links To Science

Webber MA, Buckner MMC, Redgrave LS, et al. Quinolone-resistant gyrase mutants demonstrate decreased susceptibility to triclosan. Journal of Antimicrobial Chemotherapy. Published online July 3 2017



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by GetDoc Team

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