In modern science, breakthrough results are often achieved by integrating knowledge and insights across diverse disciplines. This very approach underpins the new scientific hub established at the University of Georgia, which brings together three distinct fields: molecular medicine, One Health, and synthetic biology. The initiative aims to integrate Georgia’s scientific potential onto the international stage.
A pivotal component of this concept is the One Health Institute, founded in 2024 and built upon the modern paradigm that human, animal, plant, and environmental health are intrinsically interconnected. Dr. Mamuka Kotetishvili, Doctor of Biological Sciences and Director of the One Health Institute, discusses the institute’s objectives, significance, and the international achievements accomplished by the Georgian research team.
Dr. Kotetishvili, what are the primary research directions of the One Health Institute, what projects are currently underway, and how would you evaluate the institute’s first two years?
Over these two years, we have carried out extensive research across several core areas. These include the molecular-genetic mechanisms of antimicrobial resistance (AMR), the evolutionary divergence and dynamics of resistance genes, the evolution of human and animal pathogens, and the genomic study of bacteriophages.
I can confidently say that these efforts have yielded substantial success. Our findings have already been published in prestigious, high-impact international journals such as Frontiers in Microbiology, Springer Nature’s BMC Microbiology and Scientific Reports, as well as Oxford Academic’s Virus Evolution. Each of these falls into the Q1 category—ranking within the top 25% of scientific journals worldwide. To date, we have published eight scientific papers across these outlets, representing a milestone achievement, particularly within the context of Georgia.
Could you elaborate on the core substance of these studies? What key findings regarding antimicrobial resistance have you shared with the global scientific community through these publications?
One of our primary goals was to explore microbial networks—encompassing both human and animal pathogens as well as non-pathogenic microbes that do not cause disease themselves, but can serve as reservoirs and dissemination sources for antimicrobial resistance genes. We sought to map these AMR transmission networks and elucidate the pathways through which resistance genes disseminate.
Our investigations placed significant emphasis on genes conferring resistance to tetracyclines and macrolides. We uncovered a compelling pattern: our data suggest that some of these genes evolve via codon usage optimization. By better aligning with the pathogen’s intrinsic molecular-genetic machinery, this optimization may enhance their expression levels, potentially driving higher levels of antibiotic resistance within bacterial populations.
Antibiotic resistance is one of the world’s most pressing crises; the World Health Organization projects that by 2040, an additional 30 million lives could be lost to this issue. What biological and environmental factors fuel this escalating resistance, and what practical applications do your findings offer for prevention?
When examining molecular-genetic mechanisms, the crux of the problem becomes apparent. Biology follows a distinct pattern: under antimicrobial selection pressure, a pathogen acquires resistance genes or undergoes adaptive mutations to survive. However, once removed from the antimicrobial environment, it frequently sheds these resistance determinants. Paradoxically, while resistance elements facilitate bacterial survival under drug exposure, many of them impose a fitness cost, impairing replication efficiency and other vital physiological functions.
Our research reveals that certain resistance genes disseminate across bacterial species and even across genera. These genes not only confer protection against antibiotics but, as our findings suggest, also enhance the pathogen’s broader ecological fitness—facilitating environmental survival and colonization. Under this dynamic, pathogens no longer shed these determinants; they retain them permanently, rendering them markedly more resilient and hazardous to human and animal health.
In terms of practical application, we comprehensively characterized the interspecies and intergeneric microbial networks harboring these genes, identifying both donor and recipient taxa across global natural populations. Crucially, we pinpointed ostensibly “benign” commensals (such as non-pathogenic gut bacteria) that serve as active donors of resistance determinants. Our in silico modeling analyses, which forecast transmission trajectories, indicate that upon entering the human intestinal tract, pathogenic strains can acquire resistance genes directly from these commensal donors. Pinpointing these bacterial networks and transmission sources is critical for public health surveillance, enabling authorities to anticipate threats and design targeted prevention strategies.
Beyond antimicrobial resistance, part of your research centers on bacteriophage genomics. What differences were uncovered between the major phage lifestyles?
Bacteriophages are fundamentally categorized by their life cycles into virulent (lytic) and temperate phages. Virulent phages are widely harnessed in pharmaceuticals, veterinary medicine, biocontrol, and food safety. Conversely, temperate phages are generally avoided in applications because they frequently serve as vectors mediating the horizontal transfer of virulence factors, pathogenicity determinants, and antimicrobial resistance genes.
We aimed to interrogate genomic differences between these two phage cohorts, particularly regarding their molecular-genetic mechanisms of translational adaptation. Our in silico genomic analyses revealed an intriguing insight: in most cases (though not universally), codon usage in virulent phages is optimized for more efficient replication and translational adaptation within their bacterial hosts. Alongside other molecular-genetic mechanisms, this provides a biological explanation for the fundamental operational differences between these two phage classes.
A founding vision of the scientific hub and institute—championed by the late Mr. Tsotne Javakhishvili—was the integration of young Georgian scientists into the global scientific community. What role do early-career researchers play in your work?
Our institute is primarily driven by early-career researchers, ranging from PhD and Master’s candidates to undergraduate students. We follow a clear principle: regardless of their academic degree, each young researcher is entrusted with their own distinct project. Alongside myself, Dr. Tinatin (Tiko) Elbakidze, who heads the Laboratory of Microbial Genetics and Ecology, and Saba Kobakhidze, MPH, who leads the In Silico Laboratory of Functional Genomics and Proteomics, work side by side with them, providing mentorship and strategic direction. However, the bulk of the investigative work is carried out independently and executed brilliantly by these young scientists.
Young researchers actively involved in these studies include Megi Tsereteli, Lilia Jimsherishvili, Davit Janelidze, Ana Gamkrelidze, and Teona Kheladze. Their contributions were so substantial that they rightfully earned first-author positions on the published papers. This recognition provided a major boost to their career trajectories: over the past two to three years, four researchers from our team won competitive grants and enrolled in Master’s or doctoral programs at leading international institutions, including the University of Bonn. Similarly, I would like to highlight the success of Gvantsa Bragvadze, a researcher at the Tsotne Javakhishvili Institute of Synthetic Biology at the University of Georgia, who received an invitation from a renowned university in London. While this reflects significant international recognition, our parallel goal is to retain a strong core scientific team locally, with the expectation that researchers will return after gaining international experience to continue their work in Georgia.
As for Mr. Tsotne Javakhishvili, who is sadly no longer with us—his vision endures and has produced tangible results. While Tsotne was still with us, we maintained active communication and jointly designed a comprehensive study on antimicrobial resistance. Nino Kuchuloria, one of his talented young researchers, was closely involved in this project. The research was successfully concluded and subsequently published in a prominent Western scientific journal.
What are the institute’s current priorities, and what upcoming studies can we anticipate?
At present, we are pursuing several compelling new avenues:
The first line of inquiry focuses on genetic loci encoding prion-like proteins across bacterial populations. To clarify, these are distinct from prions responsible for neurodegenerative diseases in humans; bacterial prions predominantly facilitate microbial environmental adaptation, aligning more closely with microbial ecology. We are investigating whether loci encoding prion-like proteins in enteric bacteria play a role in inducing or provoking severe intestinal inflammatory pathologies in humans.
Our second major project examines the pathogen Brucella abortus, carried out in collaboration with colleagues from Chongqing Medical University in China. We sequenced and analyzed the genomes of both Georgian and Chinese isolates, delineating their molecular mechanisms of evolutionary divergence, genetic kinship, and estimated divergence timelines. Concurrently, using computational in silico approaches, we are investigating an unaddressed frontier: the translational adaptation mechanisms of genes encoding transposases, which are key mobile genetic elements. In natural bacterial populations, transposons actively drive the acquisition and enhancement of virulence, pathogenicity, antimicrobial resistance, and ecological adaptability. We are analyzing codon usage trends within predominant transposase-encoding genes to identify signatures of translational selection. Insights from this work will clarify the evolutionary trajectories of this pathogen, informing global control and containment efforts.
Additionally, we continue our comparative genomic research into temperate versus virulent phages. Concurrently, our wet lab facility is approaching completion, where we plan to conduct metagenomic profiling of bacterial communities across Georgia’s recreational waters, rivers, and lakes to evaluate their role as natural environmental reservoirs of antimicrobial resistance.
Looking forward, what are the institute’s long-term objectives and the scope of its international partnerships?
Moving forward, our objective is to expand our capacities in microbial phylogenetics and genomic surveillance. In Georgia, the population-genetic architectures of foodborne, zoonotic, and human bacterial and viral pathogens remain largely uncharacterized. Without these baseline genomic datasets, designing targeted, high-efficacy prevention and containment strategies against infectious diseases is exceptionally difficult.
Regarding international engagement, our expertise has drawn significant interest from foreign institutions. Beyond our partnership with Chongqing Medical University—where we have delivered presentations and Dr. Tinatin Elbakidze conducted an introductory bioinformatics course for students—an associate professor from a Turkish university completed bioinformatics training with us this year, initiating a collaborative in silico research project. Most recently, the Kazakh National Agrarian Technical University reached out to invite our team to serve as external international co-advisors on doctoral research investigating pathogen dissemination and antimicrobial resistance across animal and human populations.
Furthermore, our institute is a member of the European One Health Association, which unites leading European universities and public health bodies. Under the auspices of this association, we are hosting an international conference and workshop at the University of Georgia on November 5–6, bringing together Georgian scientists and distinguished colleagues from Europe and the United States.
