Recently I was discussing the issue of antibiotics in the environment with someone on this site who I rather enjoy - many of my interactions here are, um, unpleasant and frankly depressing to the point of hopelessness - about the issue of the ubiquity of antibiotic use. We were discussing the issue of whether the age of antibiotics is likely to be short lived, owing to the development of resistance, by evolutionary mechanisms. My friend, who, however we might differ on particular, joins me in deploring the rise in popular contempt for science, suggested that antibiotic resistance is an ancient matter, and that modern technology will allow humanity to keep ahead in the biochemical race to find new antibiotics as old ones become useless. I on the other hand am not so sanguine on that topic.
For the record, my grandmother died as a relatively young woman around the time of the Second World War from a bacterial infection that would have easily been cured just a few years after her death by an antibiotic prescription. She left 10 children and a husband. One of those children was my mother.
I won't live to see this whole game played out, but, I do think that there is cause for concern on this score, the long term viability of the "age of antibiotics."
Today I was reading the ASAP sections of one of my favorite journals, Environmental Science and Technology a publication of the American Chemical Society and came across a paper that relates to this topic. The paper I will discuss tonight in this brief diary is entitled, Toxicity and Reductions in Intracellular Calcium Levels Following Uptake of a Tetracycline Antibiotic in Arabidopsis
Right now in this country, according to the text, 27.85 million pounds (about 13,000 metric tons) of the antibiotics are sold each each year. Of this, about 38% is used in is in the general class of tetracyclines, and the majority of this 38% is used in animal feed.
Tetracyclines, it turns out, are highly stable in the environment, and degrade rather slowly, and as a result, they tend to accumulate in some media. Agricultural fields that have been fertilized with animal manure for instance have show concentrations as high as 20 mg/kg in the soils of chlortetracycline.
The authors cited a recent paper showing that tetracyclines are routinely found in Colorado River water, which of course, supplies the drinking water supplies for much of the American Southwest. (This is not by the way, meant to imply that there are toxicological implications of these concentrations, but they are routinely detectable.)
The concern of course, is that these low level concentrations can and do lead to resistant species. For the record there are now strains of things like, say, tuberculosis, for which few - and in some case no - antibiotics can treat.
The authors of the paper I reference here however were not concerned so much with resistant species but rather sought to review a toxicological implication of this widespread accumulation.
Arabidopsis is a flowering plant - native to Europe and Asia - that has a particularly small genome, and - for this reason is often used as a laboratory investigation species, much as the simple organism Drosphilia - the fruit fly - is used to study animal species.
If you have ever had a prescription for tetracycline, you may have been advised not to take it with milk. The reason for this is that tetracycline strongly interacts with calcium. Apparently this happens when tetracycline interacts with cells of the Arabidopsis plant.
Some excerpts from the text:
CTC Toxicity in Arabidopsis. For this study plants were
exposed to the highest levels detected in contaminated field soils, 20 mg/kg.7 Treated plants began to show toxicity effects after 34 days of CTC exposure, including stunted growth, reduced leaf expansion, and yellowing. These effects were not observed in control (untreated) plants. Figure 1 (top two panels) shows a comparison of CTC-treated versus untreated plants after 9 days of CTC watering. The CTC-treated Arabidopsis clearly showed toxicity effects (left panel), with reduced overall weights (right panel) when compared to control plants...
...Uptake of TC and CTC from roots into leaves was investigated by analyzing leaf extracts from plants treated with these antibiotics using liquid chromatography/mass spectrometry (LC/MS)...
...Whereas only small differences between treated and untreated Arabidopsis were observed for the representative proteins described above, there were detectable differences in accumulation of the NAD-dependent malic enzyme (NAD-ME). The accumulation of this protein was reduced approximately 2=3 fold (determined using phosphorimager quantification) in the leaves of 9-day treated plants, relative to control plants (Figure 2B, N, middle panel). At the same time, NAD-ME protein levels in roots of CTC-treated plants increased approximately 2 - 3 fold over control plants (Figure 2C, N, middle panel). In contrast, another mitochondrial enzyme, the organelle-encoded CoxII, did not shown any changes in abundance (Figure 2A, Co, bottom panel)...
...Chelation of Intracellular Calcium by CTC. Calcium chelation in plants by TC antibiotics is well-known2325 and calcium signaling affects many aspects of plant evelopment and gene expression, especially those relating to abiotic stress.4146 For this study we made use of transgenic Arabidopsis that constitutively expresses a YC3.6 cameleon protein47 from a CaMV 35-S promoter, to measure FRET in response to CTC exposure
Oh. Oh. Transgenic species. Someone should call the assholes at Greenpeace about this.
The use of these transgenic species did = I'll not bore you with the details - that certain calcium dependent proteins were reduced significantly using tetracycline, and this effect was supported by showing even greater reductions in growth using other calcium chelating agents.
It is known, by the way, that not all species are affected in the same way by tetracyclines. Some species of corn seem not to be affected while other species, like pinto beans, are affected.
Interesting paper, and I thought in this brief throwaway diary I'd discuss it. The accumulation of other pharmaceuticals in the environment, by the way, is now well known and this is simply one example of this issue.