Researchers claim that antibiotics may not be able to sterilize a bacterial culture completely and that a small subpopulation of less than 1% of bacteria (persisters) can survive antibiotic treatment which, on removal of antibiotic, may undergo phenotypic shift and cause infections. Some strategies have been proposed to eliminate persisters that have the potential in the treatment of chronic infections and biofilm-related infections. One of the strategies is to wake the persisters from dormancy and make them succeptible to antibiotics.
Allison et al. (2011) proposed that addition of specific metabolites can kill persisters when given along with aminoglycosides. They reported that metabolites such as glucose, fructose or mannitol can induce proton motive force in persisters which will help in the uptake of aminoglycosides resulting in their killing. They noticed that this strategy might work in vivo also. In their experiment, catheters colonized with E.coli biofilms were implanted in the urinary tracts of mice and treated with antibiotic (gentamicin) alone and also with a combination of antibiotic and mannitol. After three days of treatment, catheter tubing was extracted to determine biofilm viability and kidneys were removed to determine bacterial load. They found that gentamicin alone was not effective, whereas gentamicin in combination with mannitol reduced the viability of the catheter biofilms by nearly 1.5 orders of magnitude. They also found that the kidney bacterial load was approximately 107 cfu/g of kidney for untreated animals, slightly higher than 106 cfu/g for gentamicin alone treatment group but only 105 cfu/g of kidney for the combination treatment group. Based on these findings, authors claimed that in vivo results demonstrate the feasibility of their approach for clinical use.
However, were the researchers able to eliminate persisters? Persisters are a small subpopulation of less than 1% bacteria that can survive antibiotic therapy and which undergo phenotypic shift once the antibiotics are removed. The number of bacteria that survived the combination treatment was still more than 1% of the total population of untreated control. How can the researchers claim that the above approach was successful against persisters?
What will happen to the 106 cfu/g of kidney that persisted following gentamicin alone treatment? Once the antibiotic is removed from the body, those persisters will undergo ‘phenotypic shift’, re-grow and cause infection.
And what will happen to the 105 cfu/g of kidney that persisted following the combination therapy? The same…..
Hence, is there any difference between antibiotic alone treatment and combination treatment as far as re-growth of persisters and treatment of biofilms or chronic infections are concerned? No...
In order to claim that their strategy is effective, the researchers should either
a. be able to sterilize the biofilms without leaving any persisters or
b. assume that 100% bacterial killing is not necessary (i.e. a reduction in bacterial load is sufficient for successful treatment). However, if this is the case, what is the significance of persisters?
Next- Can a spoonful of sugar helps in the treatment of persistent infections?
Allison et al. (2011). Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473: 216-220
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