Sep 17, 2007

Antibiotics and viruses: a natural alliance?

At the right concentration, an antibiotic may be effective enough to kill a microbe, or at least to stop its growth. But lower antibiotic concentrations may have subtler effects on microorganisms. For instance, some bacteria respond in a funny way to very low, sub-lethal amounts of those antibiotics inhibiting cell division (such as penicillins): instead of dividing, cells become longer and longer, forming filaments. In this situation, cells are stressed but alive and still growing. Now, researchers from Université Paul Sabatier-Toulouse, France, have noticed that bacterial viruses (or phages) have also adapted to these circumstances.

ResearchBlogging.orgWhen infected by these viruses, filamenting cells produce more offspring phages than the "healthier" cells do. The increased production of phages seems to be the result of faster lysis (due to defects on cell wall caused by the antibiotic) and a higher phage assembly. From the point of view of a phage making its living off bacteria, filamenting cells might be a warning sign: "hey, watch out, something is going wrong, the cells may die soon, so we better sack the place while we can."

The discovery of this phenomenon (where serendipity played a part) may have implications for medicine and biotechnology. For instance, the use of a combination of antibiotics and phages might be a new effective treatment for some bacterial infections. But the findings also bring out a possible, unexpected relationship between antibiotics and phages in the natural environment. It suggests that phages may work as amplifiers of the deadly effects of antibiotics, which are naturally produced by microorganisms such as actinomycetes. Both the phage and the antibiotic producer get some benefit: the former gets an extra burst from its unhealthy, filamenting host; while the latter gets rid of bacterial rivals in the neighborhood. Here, the antibiotic- and phage-sensitive bacteria get the worst part. But it's a cruel world.

Comeau, A.M., Tétart, F., Trojet, S.N., Prère, M., Krisch, H.M., Fox, D. (2007). Phage-Antibiotic Synergy (PAS): β-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth. PLoS ONE, 2(8), e799. DOI: 10.1371/journal.pone.0000799

Image: The PAS effect of phage ΦMFP on Escherichia coli MFP. Disks containing the β-lactam antibiotics (indicated by “+” symbols) produced large phage plaques in their proximity.

On Sept. 19, I added the following comment at the article site:

In addition to the potential implications for medicine (i.e., antibiotics+phages combination therapy), I like the thought-provoking idea of a possible co-evolution of certain traits in antibiotic-producing microbes and in phages infecting antibiotic-sensitive bacteria. One can imagine (have a look at Figure 1) several concentric, inhibition zones surrounding the cells (or mycelia) of an antibiotic producer. Inner zones, where antibiotic concentration is deadly for different microbes (depending on their respective sensitivities). And outer zones, where the antibiotic concentration is only sub-lethal but stimulate phage production in sensitive phage-microbe couples; we might picture it as a "defensive barrier" consisting of a higher local concentration of phages, ready to attack sensitive newcomers. Given that we really don't know the antibiotic concentrations that are actually produced by microorganisms in natural environments (at least I don't know), the sub-lethal effects of secondary metabolites may be more significant than their "antibiotic" effects. Just let your imagination fly...

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