Researchers at Boston University have reported (Nature) a new adjuvancy effect – the use of sugars to enhance the behavior of (aminoglycoside) antibiotics.  Dr James Collins, along with co-researchers Drs. Allison and Brynildsen, all also affiliated with the Howard Hughes Medical Institute, as well, went about trying to determine how to kill persistent microbes survive in biofilms.  Thinking the bacterial cells were dormant, they considered adding various sugars to the antibiotic mixes.  It was hoped the presence of the sugars would “activate” the dormant cells, and, as they were now active, they would be killed off by the antibiotics.

The results proved the test- but not the hypothesis.  If the cells were dormant, it would take some time for the sugars to “activate” them; however, antibiotic kill enhancements were observed after times as short as 1 hour.   (Antibiotics kill growing cells; they destroy the cell walls or disrupt critical cellular metabolism.)  Cells would not begin actively dividing, after such a short incubation period.

It turns out that the addition of the sugars promotes hydrogen ion transport across the cell membrane (which generates ATP, the energy source of the cells).  This is called a ‘proton motive force’, which is a component in the  aminoglcoside uptake in cells.  The phenomenon also explains why there was no adjuvant effects observed for the β-lactam-active antibiotic, ampicillin, or the fluoroquinolone, ofloxacin.  Neither of these types of antibiotics involve proton motive forces.

The results were found to be enhanced for both E. coli and Staphylococcus aureus.  Using the adjuvant combination augmented the effects of gentamycin 50 fold (mannitol) for E. coli and 100 fold (fructose)  for  S. aureus.  This finding should prove useful in the treatment of recalcitrant microbial infections (such as MRSA).

This effect may also be of use in the treatment of cystic fibrosis (CF) patients.  The problem with CF patients is that the mucus in their lungs is very viscous (sticky, slow to move, like thick motor oil); the microbes that are entrained in the lung mucosa cannot be expelled, as would be done for normal patients.  This is why nearly all young CF patients have Pseudomonas infections; the microbes form biofilms in the mucus and the patient succumbs to those infections.  By adding mannitol to the antibiotic concoction, an aerosolized administration could help eradicate this problem, as well.

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