Mutational and transcriptomic changes involved in the development of macrolide resistance in Campylobacter jejuni.

Dec 2012

Hao H, Yuan Z, Shen Z, Han J, Sahin O, Liu P, Zhang Q.

Source

National Reference Laboratory of Veterinary Drug Residues(HZAU)/MOA Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan 430070, P. R. China.

Abstract

Macrolide antibiotics are important for clinical treatment of infections caused by Campylobacter jejuni. Development of resistance to this class of  antibiotics in Campylobacter is a complex process and the dynamic molecular changes involved in this process remain poorly defined. Multiple lineages of macrolide-resistant mutants were selected by stepwise exposure of C. jejuni to escalating doses of erythromycin or tylosin. Mutations in target genes were determined by DNA sequencing and the dynamic changes in the expression of antibiotic efflux transporters and the transcriptome of C. jejuni were examined by real-time RT-PCR, immunoblotting, and DNA microarray. Multiple types of mutations in ribosomal proteins L4 and L22 occurred in the early stepwise selection. On the contrary, the mutations in 23S rRNA gene, mediating highly resistant to macrolides, were only observed in the late-stage mutants. Upregulation of antibiotic efflux genes was observed in the intermediate-level resistant mutants, and the magnitude of upregulation declined as the occurrence of mutations in the 23S rRNA. DNA microarray analysis revealed differential expression of 265 genes, most of which occurred in the intermediate mutant, including upregulation of genes encoding ribosomal proteins and downregulation of genes involved in energy metabolism and motility. These results indicate 1) that mutations in L4 and L22 along with temporal overexpression of antibiotic efflux genes precede and may facilitate the development of high-level macrolide resistance and 2) that the development of macrolide resistance affects the pathways important for physiology and metabolism in C. jejuni, providing an explanation for the reduced fitness of macrolide-resistant Campylobacter.

PubMed

Soil Bacteria May “Eat” Antibiotics

Soil Bacteria May “Eat” Antibiotics

By Dan Cossins | December 10, 2012

Long-term exposure to antibiotics from agricultural run off may encourage the evolution of soil bacteria that break down and consume the antibacterial agents.

Soil microbes exposed to antibiotics over a long period evolve the ability to detoxify the compounds, and may even derive nutritional benefit in the process, according to a report out last week (December 6) in the Journal of Environmental Quality.

Antibiotics administered to promote the growth and health of livestock find their way into agricultural soils through the manure of the treated animals, which is used as fertilizer. To see how long-term exposure to these medicines affect bacteria in the soil, researchers set up an experiment more than a decade ago in which plots of land were dosed every year with a mixture of three common veterinary antibiotics—sulfamethazine, tylosin, and chlortetracycline.

Ten years on, the team found that sulfamethazine and tylosin were degraded much more rapidly in soils with a history of antibiotic exposure than in untreated soils, suggesting that antibiotic-degrading microbes are selected for over time. They also found that residues of sulfamethazine were quickly mineralized to carbon dioxide in exposed soils, but not in controls, and subsequently isolated from the treated soil a new strain of Microbacterium, a microbe that uses sulfamethazine as source of carbon and nitrogen.

The findings led the team to propose that under the selective pressure of long-term exposure to antibiotics, microbes may evolve to not only break down the compounds, but also to use them to fuel its own growth. “I think it’s kind of a game changer in terms of how we think about our environment and antibiotic resistance,” lead study author Edward Topp of Agriculture and Agri-Food Canada in London, Ontario, said in a press release.

And although the evolution of antibiotic-eating bacteria means that drugs from agricultural wastes will not linger in the soil for long, the researchers warn that the trait could be transferred to a pathogenic microbe. “A reservoir of antibiotic resistance genes in the environment that is made larger through contamination with agricultural wastes may represent an enhanced threat to human health,” the authors wrote.

The Scientist