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Ortiz de Ora, L.

Publications and source records attributed to Ortiz de Ora, L..

4 recordsLinked to original sources

Capsular Polysaccharide Safeguards a Prophage-Bacterium Symbiosis by Preventing Collateral Attack and Promoting Viral Transmission

Many symbioses exist along a continuum from cooperation to conflict. Latent bacterial viruses known as prophages embody this duality. Acting as both partner and predator, they can enhance bacterial fitness while retaining the capacity to kill their hosts through lytic replication. Yet what determines the balance between cooperation and conflict in prophage-bacterium symbioses, and how these associations avoid collapse, remains poorly characterized. To identify mechanisms that stabilize prophag-bacterium partnerships, we used experimental evolution to perturb a natural association through repeated cycles of transmission and reinfection. This perturbation consistently selected mutant hosts lacking capsular polysaccharide production and exposed a hidden conflict that proved detrimental to both partners. During lytic outbreaks, host cells suffered lethal collateral prophage attack while dispersing virions became entrapped on neighboring cells and lysis debris, severely restricting transmission. Genetic and imaging-based studies revealed that capsular polysaccharides suppress these maladaptive interactions by limiting phage readsorption at the cell surface. We term this host-mediated safeguard the Hyperion effect, after the Greek Titan of light. Hyperion interactions enable phages to radiate outward from host populations, thereby averting collateral attack and promoting viral transmission. Our findings demonstrate that conflicts between prophages and their hosts can extend beyond individual cells to whole populations, with consequences that scale to shape patterns of prophage spread and microbial community assembly. More broadly, our work illustrates how mutually beneficial prophage-bacterium interactions can arise not only through cooperation, but also through the suppression of mutually detrimental conflicts.

microbiology↗

Imaging the impact of rotifer consumption on bacterial behaviors in the zebrafish gut

The gut microbiota influence many aspects of their hosts health and physiology including the digestion of food, and food intake in turn influences the composition of the gut microbiome. However, the ways in which food can alter the behavior of intestinal bacteria remain largely unknown, due in large part to the difficulty of assessing behavior in situ. Larval zebrafish provide a model for addressing this gap because of their optical transparency and their ability to be prepared germ-free and then associated with specific microbial species. Using light sheet fluorescence microscopy to visualize bacteria inside the intestines of live zebrafish larvae, we examine the properties of two commensal strains with markedly different physical characteristics. One is a zebrafish-commensal Enterobacter species that forms large aggregates in unfed larvae, and the other is a pathobiont Vibrio species that is motile and planktonic. Following host consumption of rotifers, a common food, Enterobacter clusters disintegrate into motile individuals. Vibrio remains planktonic in fed larvae but decreases the activity of its Type VI Secretion System, leading to a strong decrease in damage to host tissue. Our results reveal that feeding can have major impacts on bacterial behavior that should be considered in models of normal gut microbiome dynamics as well as pathogenesis.

microbiology↗

Phollow: Visualizing Gut Bacteriophage Transmission within Microbial Communities and Living Animals

Bacterial viruses (known as "phages") shape the ecology and evolution of microbial communities, making them promising targets for microbiome engineering. However, knowledge of phage biology is constrained because it remains difficult to study phage transmission dynamics within multi-member communities and living animal hosts. We therefore created "Phollow": a live imaging-based approach for tracking phage replication and spread in situ with single-virion resolution. Combining Phollow with optically transparent zebrafish enabled us to directly visualize phage outbreaks within the vertebrate gut. We observed that virions can be rapidly taken up by intestinal tissues, including by enteroendocrine cells, and quickly disseminate to extraintestinal sites, including the liver and brain. Moreover, antibiotics trigger waves of interbacterial transmission leading to sudden shifts in spatial organization and composition of defined gut communities. Phollow ultimately empowers multiscale investigations connecting phage transmission to transkingdom interactions that have the potential to open new avenues for viral-based microbiome therapies.

microbiology↗

Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation and Neurodegeneration

Parkinsons disease (PD) etiology is associated with aggregation and accumulation of -synuclein (- syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that in certain subtypes of PD, -syn aggregates originate in the gut and subsequently spread to the brain. However, the mechanisms that instigate -syn aggregation in the gut have remained elusive. In the brain, the aggregation of -syn is induced by oxidized dopamine. Such a mechanism has not been explored in the gastrointestinal (GI) tract, a niche harboring 46% of the bodys dopamine reservoirs. Here, we report that gut bacteria Enterobacteriaceae induce -syn aggregation. More specifically, our in vitro data indicate that respiration of nitrate by Escherichia coli K-12 yields nitrite, a potent oxidizing agent that creates an oxidizing redox potential in the bacterial environment. In these conditions, Fe2+ was oxidized to Fe3+, enabling formation of dopamine-derived quinones and -syn aggregates. Exposing nitrite, but not nitrate, to enteroendocrine STC-1 cells induced aggregation of -syn that is natively expressed in these cells, which line the intestinal tract. Finally, we examined the in vivo relevance of bacterial nitrate respiration to the formation of -syn aggregates using Caenorhabditis elegans models of PD. We discovered that nematodes exposed to nitrate-reducing E. coli K-12 displayed significantly enhanced neurodegeneration as compared to an E. coli K-12 mutant that could not respire nitrate. This neurodegenerative effect was absent when -syn was mutated to prevent interactions with dopamine-derived quinones. Taken together, our findings indicate that gut bacterial nitrate reduction may be critical to initiating intestinal - syn aggregation. Table of Contents Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/495350v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@258b2org.highwire.dtl.DTLVardef@d3b42org.highwire.dtl.DTLVardef@ad6b1borg.highwire.dtl.DTLVardef@152d39b_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗