Cholera Bacteria Kills Neighbors To Acquire Antibiotic Resistance Genes

Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne SwitzerlandMedicalResearch.com Interview with:
Melanie Blokesch PhD

Assistant Professor (tenure-track)
Laboratory of Molecular Microbiology
Global Health Institute, School of Life Sciences
Swiss Federal Institute of Technology Lausanne (EPFL)
Lausanne Switzerland

Medical Research: What is the background for this study? What are the main findings?

Dr. Blokesch: We have been studying the cholera-causing bacterium Vibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes of horizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information.

Medical Research: What are the main findings?

Dr. Blokesch: The main finding of our study is that the pathogen V. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes – killing of other bacteria and DNA uptake – are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it.

Medical Research: What should clinicians and patients take away from your report?

Dr. Blokesch: There is still a long way to go until we fully understand this process and can act accordingly. However, another important finding of our study was that the killing device (and the DNA uptake machinery) was triggered by a natural polysaccharide, chitin, which is the most abundant polymer in aquatic environments (e.g, it makes up the shell/exoskeleton of small crustaceans). Indeed, V. cholerae is a natural inhabitant of such environments and is therefore primarily transmitted to humans by contaminated water. It is tempting to speculate that the bacterium’s association with chitinous surfaces followed by the production of the killing device could render the bacteria more pathogenic when ingested by humans as it could kill the protective commensal bacteria in the human gut. Therefore, filtration methods that remove larger (chitinous) particles might be a good way to at least partially protect people from cholera infections. Indeed, such filtration studies have been performed by Rita Colwell (University of Maryland) and her collaborators in rural villages of Bangladesh. The scientists reported that folding sari cloth a few times followed by the filtration of water through them could remove V. cholerae bacteria attached to particles and significantly lower the number of cholera patients in this endemic area.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Blokesch: There is so much we don’t know yet about the causative agent of cholera even though the disease itself has been extensively studied over the last 100 years. Thus, in the future we and probably also others will focus on elucidating the environmental lifestyle of the pathogen. This will allow us to acquire new insights into cholera transmission and to better understand how an innocuous aquatic bacterium evolved towards being a dangerous human pathogen.

Citation:

The type VI secretion system of Vibrio cholerae fosters horizontal gene transfer
Sandrine Borgeaud, Lisa C. Metzger, Tiziana Scrignari, Melanie Blokesch
Science 2 January 2015:
Vol. 347 no. 6217 pp. 63-67
DOI: 10.1126/science.126006