Uri Gophna

Tel Aviv University | TAU · School of Molecular Cell Biology and Biotechnology

Cheater viruses cannot replicate on their own yet replicate faster than the wild type (WT) when the two viruses coinfect the same cell. Cheaters must possess dual genetic features: a defect, which leads to their inability to infect cells on their own, and a selective advantage over WT during co-infection. Previously, we have discovered two point-mu...

Archaeal viruses predominantly exhibit a chronic lifestyle, where viral particles are released without causing host cell death. Therefore, conventional plaque assays, which are well-suited for identifying lytic viruses, usually fail to detect chronically infecting viruses due to their non-lytic nature. To address this limitation, we developed an op...

CRISPR-Cas is a sophisticated defence system used by bacteria and archaea to fend off invaders. CRISPR-Cas systems vary in their Cas protein composition and have therefore been divided into different classes and types. Type I systems of bacteria have been shown to contain the small Cas11 protein as part of the interference complex. Here we show for...

Many cyclic-oligonucleotide-based antiphage signalling systems (CBASS) defend against viral infections using a TIR-SAVED domain protein that depletes cellular NAD ⁺ levels, eventually leading to cell dormancy or death. This abortive infection strategy is beneficial in stopping fast lytic infections, as cells die before spreading the virus to neighb...

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally f...

Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAF...

In this study, we use pan-genomics to characterize the genomic variability of the widely dispersed halophilic archaeal species Halorubrum ezzemoulense (Hez). We include a multi-regional sampling of newly sequenced, high-quality draft genomes. The pan-genome graph of the species reveals 50 genomic islands that represent rare accessory genetic capabi...

In some extreme environments, archaeal cells have been shown to have chronic viral infections, and such infections are well-tolerated by the hosts and may potentially protect against more lethal infections by lytic viruses. We have discovered that a natural Haloferax strain (48N), which is closely related to the model organism Haloferax volcanii ,...

Background Gut microbial composition in Crohn's disease (CD) is variable, changing with specific interventions. We aimed to explore the dynamics in microbial alterations in a cohort of patients with newly diagnosed Crohn's disease (ndCD) over one year. Methods This was a prospective longitudinal real-world study of patients with ndCD1 naïve to the...

Background Ultra-processed food (UPF) intake has been associated with the development of inflammatory bowel diseases (IBD), particularly Crohn’s disease (CD). Of UPF subgroups, commercially available breads showed greater risk, possibly due to the increasing presence of food additives (FA) like emulsifiers. As bread is a staple food worldwide, ofte...

Background The Mediterranean diet (MED) is hypothesized to play a protective role in Crohn’s disease (CD) etiology, yet the underlying mechanisms remain unclear. Here we explored the association between adherence to MED, CD course, clinical and inflammatory markers, and microbial and metabolite composition in patients with newly diagnosed CD. Meth...

The gill tissue of bivalve mollusks hosts rich symbiotic microbial communities that may contribute to host health. Spondylus spinosus is an invasive Lessepsian oyster in the Eastern Mediterranean Sea that has become highly abundant while constantly expanding its range northwestward. Using 16S rRNA gene amplicon sequencing, we examined how temperatu...

Inteins are mobile genetic elements that invade conserved genes across all domains of life and viruses. In some instances, a single gene will have several intein insertion sites. In Haloarchaea, the mini-chromosome maintenance (MCM) protein at the core of replicative DNA helicase contains four intein insertion sites within close proximity, where tw...

In this study, we use pan-genomics to characterize the organized variability from the widely dispersed halophilic archaeal species Halorubrum ezzemoulense . We include a multi-regional sampling of newly sequenced, high-quality draft genomes. Using the pan-genome graph of the species, we discover 50 genomic islands which represent rare accessory gen...

Background The gut microbiome might play a role in neurodevelopment, however, evidence remains elusive. We aimed to examine the relationship between the intestinal microbiome and cognitive development of school-age children. Methods This cross-sectional study included healthy Israeli Arab children from different socioeconomic status (SES). The mic...

Background: The skin microbiome is important for skin health and protection against solar damage. Sun exposure can cause long-term harm and increase the risk of skin aging and skin cancer. Here we examined the effects of daily exposure to sun radiation on the skin microbiome in order to determine whether skin microbiome bacteria can contribute to...

CRISPR-Cas systems provide heritable acquired immunity against viruses to archaea and bacteria. Cas3 is a CRISPR-associated protein that is common to all Type I systems, possesses both nuclease and helicase activities, and is responsible for degradation of invading DNA. Involvement of Cas3 in DNA repair had been suggested in the past, but then set...

Metagenomics has improved our understanding of commensal bacteria that colonize human intestines yet relies almost exclusively on fecal samples. Thus, spatial information about the niche range of these gut microbes and the level of specialized adaptation that they undergo has been inaccessible to fecal metagenomic studies. Here, we leveraged metage...

Viroids and viroid-like covalently closed circular (ccc) RNAs are minimal replicators that typically encode no proteins and hijack cellular enzymes for replication. The extent and diversity of viroid-like agents are poorly understood. We developed a computational pipeline to identify viroid-like cccRNAs and applied it to 5,131 metatranscriptomes an...

Polyploidy, the phenomenon of having more than one copy of the genome in an organism, is common among haloarchaea. While providing short-term benefits for DNA repair, polyploidy is generally regarded as an ‘evolutionary trap’ that by the notion of the Muller’s ratchet will inevitably conclude in the species’ decline or even extinction due to a grad...

Type VI secretion systems are molecular syringes used by Gram-negative bacteria to kill heterospecific (non-kin) niche competitors. In this issue of Cell, Mashruwala et al. show that colonies of the pathogen Vibrio cholera can also exhibit T6SS-mediated cell killing of kin cells and that this process benefits emerging resistant mutants, thereby inc...

The Mediterranean diet (MED) is associated with the modification of gut microbial composition. In this pilot study, we investigate the feasibility of a microbiota-targeted MED-based lifestyle intervention in healthy subjects. MED intervention integrating dietary counseling, a supporting mobile application, and daily physical activity measurement us...

Archaea remains the least-studied and least-characterized domain of life despite its significance not just to the ecology of our planet but also to the evolution of eukaryotes. It is therefore unsurprising that research into horizontal gene transfer (HGT) in archaea has lagged behind that of bacteria. Indeed, several archaeal lineages may owe their...

High-throughput RNA sequencing offers broad opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA virus contigs. Analysis of >330,000 RNA-dependent RNA polymerases (RdRPs) shows that this expansion corresponds to a 5-fold increase of the known RNA virus diversity. Gene content analysis rev...

Viruses are important ecological, biogeochemical, and evolutionary drivers in every environment. Upon infection, they often cause the lysis of the host cell. However, some viruses exhibit alternative life cycles, such as chronic infections without cell lysis. The nature and the impact of chronic infections in prokaryotic host organisms remains larg...

Most known CRISPR‐Cas systems primarily provide acquired, heritable immunity to bacteria and archaea against invasion by selfish DNA elements. Consequently, the main activity of these systems is to destroy incoming DNA that matches their immune memory–spacers within the CRISPR array. This chapter discusses, the evidence for and against such a trade...

Here, we examined the skin microbiome of two groups of healthy volunteers living on the Mediterranean coast with different exposures to sun radiation. One group, exposed to the sun in the summer, was compared with a group covered with clothing throughout the year. The seasonal effects on the skin microbiome of three body sites were determined befor...

Viroids and viroid-like agents are unique, minimal RNA replicators that typically encode no proteins and hijack cellular enzymes for their genome replication. As the extent and diversity of viroid-like agents are poorly understood, we developed a computational pipeline to identify viroid-like covalently closed circular (ccc) RNAs and applied it to...

Background and Aims Escherichia coli is over-abundant in the gut microbiome of patients with IBD. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. Methods We investigated E. coli genomes from patients with UC, CD or a pouch and healthy subjects. The majority of which were reconstructed from metagenomic samples...

Background and aims: The Mediterranean diet (MED) is associated with the modification of gut microbial composition. Here we conducted a pilot study of a microbiota targeted MED-based nutritional education program investigating its feasibility and effects on dietary habits, inflammatory markers, and microbial composition of healthy individuals. Meth...

Polyploidy, the phenomenon of having more than one copy of the genome in an organism, is common among haloarchaea. While providing short-term benefits for DNA repair, polyploidy is generally regarded as an ‘evolutionary trap’ that by the notion of the Muller’s ratchet will inevitably conclude in the species’ decline or even extinction due to a grad...

The development of the gut microbiome occurs mainly during the first years of life; however, little is known on the role of environmental and socioeconomic exposures, particularly within the household, in shaping the microbial ecology through childhood. We characterized differences in the gut microbiome of school-age healthy children, in associatio...

We thank Weaver et al¹ for the interest in our study focusing on antibiotic use patterns and safety profile in a cohort of patients with ulcerative colitis who underwent total abdominal proctocolectomy with ileal pouch–anal anastomosis.² We read with interest their letter describing antibiotic regimen choice and duration in patients with chronic an...

High-throughput RNA sequencing offers unprecedented opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA viral contigs. Via analysis of the 330k novel RNA-dependent RNA polymerases (RdRP), this expansion corresponds to a five-fold increase of RNA virus diversity. Extended RdRP phylogeny s...

Locust plagues are a notorious, ancient phenomenon. These swarming pests tend to aggregate and perform long migrations, decimating cultivated fields along their path. When population density is low, however, the locusts will express a cryptic, solitary, non‐aggregating phenotype that is not considered a pest. Although the transition from the solita...

Background Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention afte...

Objective Escherichia coli is over-abundant in the gut microbiome of patients with IBD, yet most studies have focused on the adherent-invasive E. coli pathotype. Here, we aimed to identify IBD-specific or phenotype-specific genomic functions of diverse E. coli lineages. Design We investigated E. coli from patients with UC, CD and a pouch and healt...

Introduction Pouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-...

Prolonged exposure to psychiatric pharmacological agents is often associated with marked gastrointestinal phenomena, including changes in food intake, bowel motility, gastric emptying, and transit time. Those changes are reflected in the gut microbiota composition of the patient and can, therefore, be objectively measured. This is in contrast to th...

The intestinal microbiome continues to shift and develop throughout youth and could play a pivotal role in health and wellbeing throughout adulthood. Environmental and interpersonal determinants are strong mediators of the intestinal microbiome during the rapid growth period of preadolescence. We aim to delineate associations between the gut microb...

Interest and controversy surrounding the evolutionary origins of extremely halophilic Archaea has increased in recent years, due to the discovery and characterization of the Nanohaloarchaea and the Methanonatronarchaeia. Initial attempts in explaining the evolutionary placement of the two new lineages in relation to the classical Halobacteria (also...

Background and Aims Bacterial urease is a major virulence factor of human pathogens, and murine models have shown that it can contribute to the pathogenesis of inflammatory bowel diseases [IBD]. Methods The distribution of urease-producing bacteria in IBD was assessed using public fecal metagenomic data from various cohorts, including non-IBD cont...

Background: Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention aft...

Microbial fuel cells (MFCs) generate energy while aiding the biodegradation of waste through the activity of an electroactive mixed biofilm. Metabolic cooperation is essential for MFCs’ efficiency, especially during early colonization. Thus, examining specific ecological processes that drive the assembly of anode biofilms is highly important for sh...

Crohn's disease (CD), ulcerative colitis (UC), and pouchitis are multifactorial and chronic inflammatory bowel diseases (IBD). Pouchitis develops in former UC patients after proctocolectomy and ileal-pouch-anal anastomosis and is characterized by inflammation of the previously normal small intestine comprising the pouch. The extent to which microbi...

A hallmark of the desert locust's ancient and deserved reputation as a devastating agricultural pest is that of the long-distance, multi-generational migration of locust swarms to new habitats. The bacterial symbionts that reside within the locust gut comprise a key aspect of its biology, augmenting its immunity and having also been reported to be...

Prolonged exposure to psychiatric pharmacological agents is often associated with marked gastrointestinal phenomena, including changes in food intake, bowel motility, gastric emptying, and transit time. Those changes are reflected in the gut microbiome composition of the patient and can therefore be objectively measured. This is in contrast to the...

Horizontal gene transfer is a means by which bacteria, archaea, and eukaryotes are able to trade DNA within and between species. While there are a variety of mechanisms through which this genetic exchange can take place, one means prevalent in the archaeon Haloferax volcanii involves the transient formation of cytoplasmic bridges between cells and...

The gill tissue of bivalve mollusks hosts rich symbiotic microbial communities that may contribute to the host wellbeing. Spondylus spinosus is a Lessepsian invasive oyster to the eastern Mediterranean Sea that has become highly abundant, while constantly expending its range northwestward. Using 16S rRNA gene amplicon sequencing we examined how tem...

Microbial fuel cells (MFCs) can generate electricity simultaneously with wastewater treatment. For MFCs to be considered a cost-effective treatment technology, they should quickly re-establish a stable electroactive microbial community in the case of system failure. In order to shorten startup times, temporal studies of anodic biofilm development a...

Background Mediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery. Methods Consecutive patients after pouch surgery due to ulcerative...

Crohn's disease (CD), ulcerative colitis (UC) and pouchitis are multifactorial and chronic inflammatory bowel diseases (IBD). Pouchitis develops in former patients with UC after total proctocolectomy and ileal pouch-anal anastomosis and is characterized by inflammation of the previously normal small intestine comprising the pouch. It has been shown...

As one of the world's most infamous agricultural pests, locusts have been subjected to many in-depth studies. Their ability at one end of their behavioral spectrum to live as solitary individuals under specific conditions, and at the other end of the spectrum to form swarms of biblical scale, has placed them at the focus of vast research efforts. O...

Locust plagues are an ancient phenomenon, with references going back to the Old Testament. These swarming pests are notorious for their tendency to aggregate and perform long migrations, consuming vast amounts of vegetation and decimating the cultivated fields on their path. However, when population density is low, locusts will express a solitary,...

A hallmark of the desert locust’s ancient and deserved reputation as a devastating agricultural pest is that of the long-distance, multi-generational migration of locust swarms to new habitats. The bacterial symbionts that reside within the locust gut comprise a key aspect of its biology, augmenting its immunity and having also been reported to be...

Inteins are selfish genetic elements residing in open reading frames that can splice post-translationally, resulting in the ligation of an uninterrupted, functional protein. Like other inteins, the DNA polymerase B (PolB) intein of the halophilic archaeon Haloferax volcanii has an active homing endonuclease (HEN) domain, facilitating its horizontal...

Inter-subject variability in human milk microbiome is well known; however, its origins and possible relationship to the mother’s diet are still debated. We investigated associations between maternal nutrition, milk fatty acids composition and microbiomes in mother–infant dyads. Breast milk and infant fecal samples were collected across three time p...

Cheater viruses, also known as defective interfering viruses, cannot replicate on their own yet replicate faster than the wild type upon coinfection. While there is growing interest in using cheaters as antiviral therapeutics, the mechanisms underlying cheating have been rarely explored. During experimental evolution of MS2 phage, we observed the p...

Haloferax volcanii is to our knowledge the only prokaryote known to tolerate CRISPR-Cas mediated damage to its genome in the wild type background; the resulting cleavage of the genome is repaired by homologous recombination restoring the wild type version. In mutant Haloferax strains with enhanced self-targeting, cell fitness decreases and microhom...

Horizontal gene transfer is a means by which bacteria, archaea, and eukaryotes are able to trade DNA within and between species. While there are a variety of mechanisms through which this genetic exchange can take place, one means prevalent in the archaeon Haloferax volcanii involves the transient formation of cytoplasmic bridges between cells and...

Halobacteria have been observed to be highly recombinogenic, frequently exchanging genetic material. Several barriers to mating in the Halobacteria have been examined, such as CRISPR-Cas, glycosylation, and archaeosortases, but these are low barriers that do not drastically reduce the recombination frequency. Another potential barrier could be rest...

Colibactin is a genotoxic molecule, produced primarily by Escherichia coli. Colibactin causes DNA damage that may lead to colorectal cancer. Here we review recent advances in the study of colibactin and propose a focus on patients with inflammatory bowel diseases (IBD) who have higher levels of colibactin-producing bacteria in their intestines.

The important role that locust gut bacteria play in their host biology is well accepted. Among other, gut bacteria were suggested to be involved in the locust swarming phenomenon. In addition, in many insect orders, the reproductive system was reported to serve as a vector for trans-generation bacterial inoculation. Knowledge of the bacterial fauna...

Microbial fuel cells (MFCs) are devices that can generate energy while aiding biodegradation of waste through the activity of an electroactive mixed biofilm. Metabolic cooperation is considered essential for MFCs’ efficiency, especially during early-anode colonization. Yet, the specific ecological processes that drive the assembly of an optimized a...

Antibiotic resistance is one of the major challenges facing modern medicine worldwide. The past few decades have witnessed rapid progress in our understanding of the multiple factors that affect the emergence and spread of antibiotic resistance at the population level and the level of the individual patient. However, the process of translating this...

Background: Mycoplasma bovis is an important etiologic agent of bovine mycoplasmosis affecting cattle production and animal welfare. In the past in Israel, M. bovis has been most frequently associated with bovine respiratory disease (BRD) and was rarely isolated from mastitis. This situation changed in 2008 when M. bovis-associated mastitis emerge...