Auxiliary metabolic genes expand understanding of phages and their reprogramming strategy

Viruses that infect bacteria, called bacteriophages, could be used in a targeted manner to combat bacterial diseases. They also play an important ecological role in global biogeochemical cycles. Recent research by researchers at the University of Kaiserslautern-Landau (RPTU) has identified a previously unknown auxiliary metabolic gene in aquatic phages, significantly expanding previous understanding of these bacterial predators.

The work is published in the journal Natural communications.

Phages are viruses that attack bacteria exclusively. The goal of many scientists is to learn more about these tiny replicative units measuring between 20 and 300 nm (a hair is 80,000 nm thick).

“If we understand in detail how phages end up infecting and killing bacteria, we may be able to use them specifically against harmful bacteria in the future,” explains Professor Nicole Frankenberg-Dinkel from the RPTU. The microbiology team studies the different strategies used by phages to transform bacteria into “factories” intended for their replication, that is to say the production of hundreds of new phages.

“We are particularly interested in aquatic habitats, especially oceans and lakes, because phages are present in large numbers and play an important ecological role in nutrient recycling,” explains Professor Frankenberg-Dinkel.

The long-term goal of bacteriophage research is not only to apply phage therapy to combat “bad” disease-causing bacteria, but also, sticking to aquatic habitats, to address the ecological role of phages in global nutritional cycles.

Phages play a crucial ecological role in aquatic environments by controlling bacterial populations, maintaining microbial diversity, and influencing nutrient cycling through processes such as viral shunting. They also drive microbial evolution by promoting horizontal gene transfer – the transmission from one organism to another rather than, as is usually the case, from generation to generation – and by exerting selective pressure on bacteria.

In a recent study, Frankenberg-Dinkel’s team, in collaboration with researchers from Israel, the Netherlands, Tübingen and Stechlin/Potsdam, analyzed phage genetic material from environmental samples at the help of bioinformatics.

“Normally, this genetic material mainly contains the information necessary for the production of new phage particles. The phages then use the bacteria as factories,” explains the professor.

However, the researchers also discovered “helper metabolic genes” in the phage’s genetic material. These helper genes originally come from bacteria and were once hijacked by phages. They are not necessary for the assembly of new phage particles, but rather serve to “reprogram” the host, namely the bacteria, during phage infection.

“In our study, we discovered a previously unknown auxiliary metabolic gene in phages,” says Frankenberg-Dinkel, explaining his latest results. “We were able to show that this gene codes for an active protein important for the biosynthesis of the “pigments of life”.”

Tetrapyrroles are called the pigments of life. The most important representatives of these chemical compounds are heme, a component of blood hemoglobin for oxygen transport, and chlorophyll, the green pigment in leaves essential for photosynthesis.

Frankenberg-Dinkel notes: “Our results suggest that tetrapyrroles play an important role during phage infection. They seem so important that the phages carry this extra genetic material because it is beneficial to them in some way.

“The importance of tetrapyrroles in phage infection was not known to this extent before. Tetrapyrroles are essential for energy production in cells,” continues Frankenberg-Dinkel. “We suspect that there is an increased energy demand when bacteria need to produce phage particles. Therefore, more tetrapyrroles may be needed.”

The researchers were able to demonstrate that the helper metabolic gene is present in phages identified in both salt and fresh water.

According to Frankenberg-Dinkel, the results of the current study reveal another interesting discovery: there are two ways to produce the first precursor of tetrapyrroles, one of which is the so-called Shemin pathway. And it is precisely this pathway – or rather the genetic makeup that is necessary for it – that researchers have identified in phages.

“The Shemin pathway is only found in one group of bacteria, and otherwise only in birds and mammals. This means that phages must have acquired this gene from a particular group of bacteria. Perhaps because the pathway Shemin is more effective than the C5 alternative because it only requires one enzyme instead of two,” she concludes.