Bacteria Modulate Orsay Virus Transmission and Infection in Caenorhabditis elegans

Core Concepts

Distinct bacterial species in the C. elegans microbiome can dramatically modulate the transmission and infection rates of the Orsay virus through host susceptibility mechanisms involving bacterial quorum sensing and virulence pathways.

Abstract

The study investigates how bacteria isolated from the natural environment of the nematode Caenorhabditis elegans affect the transmission and infection of the Orsay virus, a naturally occurring virus that infects C. elegans. The key findings are: Ochrobactrum species promote Orsay virus transmission, while Pseudomonas lurida MYb11 and Pseudomonas aeruginosa strains PA01 and PA14 attenuate virus transmission. The presence of Ochrobactrum vermis MYb71 reduces the amount of Orsay virus required to infect 50% of the C. elegans population by over three orders of magnitude compared to P. lurida MYb11. P. aeruginosa PA14 further attenuates host susceptibility. Genetic analysis reveals that the attenuation of Orsay virus transmission and infection by P. aeruginosa and P. lurida is dependent on bacterial quorum sensing regulators like gacA, as well as other virulence-related genes. Mutation of the gacA regulator in P. lurida MYb11 suppresses the attenuation of Orsay virus transmission and infection, suggesting a conserved role for quorum sensing in modulating virus-host interactions across different bacterial species. Electron microscopy suggests that Ochrobactrum vermis MYb71 may disrupt the intestinal brush border and glycocalyx of C. elegans, potentially promoting viral infection. Overall, the study provides quantitative evidence for the critical role of tripartite host-virus-bacteria interactions in determining viral transmission and infection rates.

Stats

The dose of Orsay virus required to infect 50% of the C. elegans population (ID50) was 14-fold higher in the presence of E. coli OP50 compared to O. vermis MYb71, and 120-fold and 1800-fold higher compared to P. lurida MYb11. The incidence proportion of Orsay virus transmission was 2.7-fold and 2.9-fold higher in the presence of Ochrobactrum species compared to E. coli OP50, and 4.1-fold and 11-fold lower in the presence of P. lurida MYb11. Mutation of quorum sensing regulators like gacA, rhlR, and lasI in P. aeruginosa suppressed the attenuation of Orsay virus infection by 6-fold to 19-fold.

Quotes

"Exposure to many of the naturally associated bacterial strains resulted in transmission that was comparable to the incidence proportion observed with E. coli OP50 with some prominent exceptions." "On average, 3.6 μL of Orsay virus stock was required to infect 50% of a population of ZD2611 animals in the presence of E. coli OP50 after 24 hours." "The ID50 observed in the presence of P. lurida was 120-fold and 1800-fold higher than the ID50 in the presence of E. coli OP50 or O. vermis MYb71 respectively."

Key Insights Distilled From

Bacteria Are a Major Determinant of Orsay Virus Transmission and Infection in Caenorhabditis elegans

by Vassallo,B. ... at www.biorxiv.org 09-05-2023

https://www.biorxiv.org/content/10.1101/2023.09.05.556377v2

Deeper Inquiries

How do the specific mechanisms by which Ochrobactrum, P. lurida, and P. aeruginosa modulate Orsay virus transmission and infection compare to the ways other microbiome constituents or pathogens may influence viral infections in other host-virus systems

Ochrobactrum, P. lurida, and P. aeruginosa exhibit distinct mechanisms in modulating Orsay virus transmission and infection, highlighting the diverse ways in which microbiome constituents or pathogens can influence viral infections in host-virus systems. Ochrobactrum species, such as O. vermis MYb71, promote Orsay virus transmission by potentially disrupting the brush border region of epithelial cells, facilitating viral entry and infection. This mechanism is reminiscent of enhancin produced by Serratia marcescens, which degrades the mucus layer covering epithelial cells in mosquitoes, promoting viral infection. On the other hand, P. lurida MYb11 and pathogenic P. aeruginosa strains, like PA01 and PA14, attenuate Orsay virus transmission and infection. These bacteria may suppress viral infection through quorum sensing systems, such as gacA, which regulate virulence factors and quorum signaling in Pseudomonads. Additionally, mutations in genes like ptsP, prpC, and kinB in P. aeruginosa PA14 can also suppress the attenuation of Orsay virus infection, indicating a complex interplay between bacterial factors and viral dynamics.

What are the broader ecological and evolutionary implications of bacteria being able to dramatically alter viral transmission and infection rates within a host population

The ability of bacteria to significantly alter viral transmission and infection rates within a host population has profound ecological and evolutionary implications. Firstly, these findings underscore the intricate interplay between host, virus, and microbiota in shaping disease dynamics. Bacteria like Ochrobactrum, P. lurida, and P. aeruginosa can act as key determinants of viral susceptibility or resistance, influencing the spread and impact of viral infections within host populations. This highlights the importance of considering the microbiome composition in understanding disease outcomes and transmission dynamics. From an evolutionary perspective, the ability of bacteria to modulate viral infections suggests a co-evolutionary arms race between hosts, viruses, and microbiota, driving the diversification of strategies to enhance or suppress viral transmission. Such interactions may contribute to the maintenance of host-microbiota-virus equilibrium and the evolution of host defense mechanisms against viral pathogens.

Could the insights gained from studying tripartite host-virus-bacteria interactions in the C. elegans model system be leveraged to develop novel antiviral strategies or improve our understanding of viral disease dynamics in human and animal populations

Insights gained from studying tripartite host-virus-bacteria interactions in the C. elegans model system hold significant potential for informing novel antiviral strategies and enhancing our understanding of viral disease dynamics in human and animal populations. By elucidating the specific mechanisms by which bacteria like Ochrobactrum, P. lurida, and P. aeruginosa modulate viral transmission and infection, researchers can identify key targets for intervention. Understanding how bacteria influence viral susceptibility in a host can lead to the development of targeted therapies that manipulate the microbiome to enhance host resistance to viral infections. Additionally, the knowledge gained from studying these interactions can provide valuable insights into the broader dynamics of viral diseases, shedding light on the complex interplay between host immunity, viral pathogenesis, and microbial factors. This knowledge can be leveraged to design more effective strategies for managing viral diseases, predicting disease outcomes, and potentially developing new antiviral therapies with broader applicability across different host-virus systems.