Non-antibiotic drugs promote antibiotic resistance

The study, published this week in Nature, has revealed an unexpected avenue by which gut bacteria can become resistant to antibiotics: exposure to drugs that were designed to act on human cells rather than microbial ones.

The researchers noticed too that the strains of bacteria most resistant to the effects of drugs not aimed at them were also those most resistant to antibiotics.They found many cases where proteins (and thus genes) which protected bacteria from these seven drugs were ones already known to make them resistant to antibiotics. (In the case of antipsychotics, these chemically diverse drugs seemed to affect many of the same strains of gut bacteria.

Some strains she looked at which were resistant to antibiotics nevertheless succumbed to one or more of the non-antibiotic drugs thrown at them.This means the gut bacteria of patients consuming (say) painkillers or proton-pump inhibitors might evolve a resistance that they then passed on to a pathogen that subsequently infected the body.

Apparently, Coli carrying tolC were resistant to the effects of both antibiotic and non-antibiotic drugs, and that E. To check if that was indeed the case, Dr Maier and her colleagues first looked at a particular strain of a common gut bacterium, Escherichia coli, which they knew carried an antibiotic-resistance gene called tolC.

Since most antibiotics are administered by mouth, the many bacteria that live peacefully in the human gut are particularly susceptible to such evolutionary pressures. They studied the effects of seven non-antibiotic drugs on each of these strains. They have then gone on to expose those cultures to hundreds of drugs for a range of ailments, at the sorts of concentrations that might be encountered in the human intestine.

This could be a starting point for the development of new antimicrobial agents which would eliminate bacteria that have proved intractable to other means. This observation implied that these bacteria were using similar means to defend themselves against both sorts of medicine.

The medical consequences of this are ill-understood, in part because most gut bacteria are anaerobes (meaning they flourish only in the absence of oxygen) and so are difficult to culture. Given that all the drugs tested have already been approved for human use, albeit for unrelated conditions, this is a path well worth exploring.

These accidental bactericides included proton-pump inhibitors such as omeprazole (used to treat acid reflux), calcium-channel blockers (to lower blood pressure), antihistamines, painkillers and antipsychotics.

Of the drugs in the study, 156 were antibacterials (144 antibiotics and 12 antiseptics).

But Lisa Maier of the European Molecular Biology Laboratory, in Heidelberg, and her colleagues have, nevertheless, grown 40 of the most common strains of them in anaerobic conditions. In sum, their work suggests that bacteria often use similar mechanisms to evade all classes of drug.

Bacteria that possess tolC can make a protein which works as an antibiotic-expulsion pump. THE widespread use of antibiotics encourages the pathogens they are directed against to become inured to their effects.