Helium Ion Microscopy Reveals Phage-Bacterium Interaction

Bacteria and viruses can be imaged with helium ions in contrast to electrons, which are the standard workhorse in nanoscale microscopy, an interdisciplinary research consortium from the Nanoscience Center at University of Jyvaskyla in Finland has found.

Helium ions, being more massive than electrons, can be focused to a much tighter spot down to the atomic length scales. By measuring the electrons generated by the ion bombardment, an image can be formed from the sample with biological features visible below the nanometer (one billionth of a meter) length.

The novel technique, known as helium ion microscopy (HIM), was used to image hard-to-see interaction between bacteria and viruses infecting bacteria, or so called bacteriophages. These phages are currently actively considered as a novel “smart weapon” against bacterial infections, which are becoming more and more difficult to treat with traditional antibiotics.

A scanning helium ion microscope (SHIM, HeIM or HIM) is an imaging technology based on a scanning helium ion beam. Similar to other focused ion beam techniques, it allows to combine milling and cutting of samples with their observation at sub-nanometer resolution.

Phage Attack

The images demonstrated in clear images the different stages of how the phages in question attacked the bacteria (E. coli), for example showing the process where the virus has latched onto the bacterial surface, grabbing it with a tentacle like structure, and being in the process of injecting its genome into the bacterial cell.

In addition to imaging, the researchers also demonstrated that the ions can be used as a nanoscale scalpel, to cut portions off individual bacterial cells, or to reveal bacterial colonies under the surfaces of samples. They feel confident that HIM offers many more possibilities in the future to help to study microbes and viruses in their natural state, interacting with each other and other cells.

Phage therapy or viral phage therapy is a therapeutic use of bacteriophages to treat pathogenic bacterial infections. Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture.

Bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism, but also to other beneficial bacteria, such as the gut flora, reducing the chances of opportunistic infections.

They have a high therapeutic index, that is, phage therapy would be expected to give rise to few side effects. Because phages replicate in vivo, a smaller effective dose can be used. On the other hand, this specificity is also a disadvantage: a phage will only kill a bacterium if it is a match to the specific strain.

Consequently, phage mixtures are often applied to improve the chances of success, or samples can be taken and an appropriate phage identified and grown.

M. Leppänen, L.-R. Sundberg, E. Laanto, G. M. de F. Almeida, P. Papponen, I. J. Maasilta,
Imaging Bacterial Colonies and Phage-Bacterium Interaction at Sub-Nanometer Resolution Using Helium-Ion Microscopy
Adv. Biosys. 2017, 1700070. https://doi.org/10.1002/adbi.201700070

Image: Bacteriophages (green) attached on E. coli bacteria (blue) on an agar substrate (brown), imaged with a helium ion microscope. Credit: University of Jyväskylä