Viruses are generally regarded as “enemies” that need to be eliminated by living organisms. However, many bacteria retain remnants of viruses in their genomes, and Assistant Professor Nagakubo has demonstrated that these remnants may confer benefits to their hosts. The present study reveals a new form of “coexistence” between organisms and viruses, and further suggests that the functions of these viral remnants have potential applications in various fields, such as antibiotic development and genome editing. 

The Roles of Viral Remnants 

Although bacteria are extremely small unicellular organisms, they possess various immune systems to eliminate invading viruses. One such system is the CRISPR/Cas system, which has been widely utilized as a genome-editing tool and was recognized with the Nobel Prize in Chemistry. 

Recent findings indicate that many bacteria retain viral genetic remnants in their genomes (Figure 1). These sequences likely derive from viruses that once infected the bacteria, escaped immune surveillance, and were retained throughout evolution. 

Figure 1. A typical virus that infects bacteria (left) consists of a head containing its genetic material and a tail that injects this material into the target cell.
In contrast, a viral remnant (right) lacks the head region and, thus, has lost its infectivity. (created by NAGAKUBO Toshiki) 

We previously demonstrated that viral remnants have undergone diverse evolutionary changes within bacteria and, in many cases, are beneficial for their host cells. Although viruses are generally regarded as “enemies” of living organisms, a long-term evolutionary perspective reveals a new relationship of “coexistence” emerging between the two. 

Potential Applications as a “Protein Delivery Tool” 

I have been investigating the functions of virus-like particles in actinomycetes, a group of soil-dwelling bacteria. The results of analyses revealed that these particles contain a wide variety of functional proteins (effectors), which are injected into the target cell through the cell membrane (Figure 2). These effectors exert multiple functions within the host bacterium, contributing to various cellular processes. 

Figure 2. Functions and mechanisms of virus-like particles 
Virus-like particles contain effectors (yellow) that are injected into the host cell through the cell membrane.
These effectors possess diverse functions, such as fragmenting genomic DNA, 
and contribute to enhancing the survival of the host bacterium. (Created by NAGAKUBO Toshiki)  

In recent years, there has been growing interest in applying this mechanism as a “protein delivery tool” capable of transporting specific proteins into target cells, with potential uses in medicine and related fields. 

　The proteins packaged within virus-like particles may be artificially replaced. For example, if a genome-editing enzyme is loaded into a virus-like particle, the particle may function as a tool for genome editing, an approach that has already been demonstrated by research teams overseas. 

　On the other hand, I am focusing on its application as an antibiotic. By enclosing proteins that attack specific microorganisms in virus-like particles, I am advancing research based on the idea that they may be used to eliminate microorganisms that cause diseases from the body or to attack specific microorganisms in the gut in order to improve the intestinal environment. 

　I am the only researcher in Japan who is examining virus-like particles in actinomycetes. This is because actinomycetes are difficult to handle, and analyzing the functions of the proteins in these particles is challenging. By making use of my experience in culturing and protein manipulation, I am building an original approach by combining a number of techniques. In addition, the virus-like particles I work with are different from those used by overseas teams, and the proteins they contain also differ; therefore, I may be able to develop tools with unique functions. 

　The functions of microorganisms may be used for various purposes because they are simple. I hope to obtain a more detailed understanding and draw out their potential value. 

　At the Microbial Sustainability Research Center (MiCS) at the University of Tsukuba, where I currently belong, we investigate microbial behavior from multiple perspectives, including physics and biochemistry. By collaborating with researchers in other fields, I hope to turn this into a project that may develop from basic research to applied research. 

(Date of interview: June 16, 2025)