More Like this

1. A bacterial quorum sensing signal is a potent inhibitor of de novo pyrimidine biosynthesis in the globally abundant Emiliania huxleyi

   https://doi.org/10.3389/fmicb.2023.1266972  

   Garrett, Oscar; Whalen, Kristen E. (October 2023, Frontiers in Microbiology)

   Interactions between marine phytoplankton, viruses, and bacteria drive biogeochemical cycling, shape marine trophic structures, and impact global climate. Microbially produced compounds have emerged as key players in influencing eukaryotic organismal physiology, and in turn, remodel microbial community structure. This work aimed to reveal the molecular mechanism by which the bacterial quorum sensing molecule 2-heptyl-4-quinolone (HHQ), produced by the marine gammaproteobacteriumPseudoalteromonasspp., arrests cell division and confers protection from virus-induced mortality in the bloom-forming coccolithophoreEmiliania huxleyi. Previous work has established alkylquinolones as inhibitors of dihydroorotate dehydrogenase (DHODH), a fundamental enzyme catalyzing the fourth step in pyrimidine biosynthesis and a potential antiviral drug target. An N-terminally truncated version ofE. huxleyiDHODH was heterologously expressed inE. coli, purified, and kinetically characterized. Here, we show HHQ is a potent inhibitor (K_iof 2.3 nM) ofE. huxleyiDHODH.E. huxleyicells exposed to brequinar, the canonical human DHODH inhibitor, experienced immediate, yet reversible cellular arrest, an effect which mirrors HHQ-induced cellular stasis previously observed. However, brequinar treatment lacked other notable effects observed in HHQ-exposedE. huxleyiincluding significant changes in cell size, chlorophyll fluorescence, and protection from virus-induced lysis, indicating HHQ has additional as yet undiscovered physiological targets. Together, these results suggest a novel and intricate role of bacterial quorum sensing molecules in tripartite interdomain interactions in marine ecosystems, opening new avenues for exploring the role of microbial chemical signaling in algal bloom regulation and host-pathogen dynamics. 

   more » « less
2. Bacterial Quorum-Sensing Signal Arrests Phytoplankton Cell Division and Impacts Virus-Induced Mortality

   https://doi.org/10.1128/mSphere.00009-21  

   Pollara, Scott B.; Becker, Jamie W.; Nunn, Brook L.; Boiteau, Rene; Repeta, Daniel; Mudge, Miranda C.; Downing, Grayton; Chase, Davis; Harvey, Elizabeth L.; Whalen, Kristen E. (June 2021, mSphere)

   McMahon, Katherine (Ed.)

   ABSTRACT Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems by controlling primary production, structuring marine food webs, mediating carbon export, and influencing global climate. Phytoplankton-bacterium interactions are facilitated by secreted compounds; however, linking these chemical signals, their mechanisms of action, and their resultant ecological consequences remains a fundamental challenge. The bacterial quorum-sensing signal 2-heptyl-4-quinolone (HHQ) induces immediate, yet reversible, cellular stasis (no cell division or mortality) in the coccolithophore Emiliania huxleyi ; however, the mechanism responsible remains unknown. Using transcriptomic and proteomic approaches in combination with diagnostic biochemical and fluorescent cell-based assays, we show that HHQ exposure leads to prolonged S-phase arrest in phytoplankton coincident with the accumulation of DNA damage and a lack of repair despite the induction of the DNA damage response (DDR). While this effect is reversible, HHQ-exposed phytoplankton were also protected from viral mortality, ascribing a new role of quorum-sensing signals in regulating multitrophic interactions. Furthermore, our data demonstrate that in situ measurements of HHQ coincide with areas of enhanced micro- and nanoplankton biomass. Our results suggest bacterial communication signals as emerging players that may be one of the contributing factors that help structure complex microbial communities throughout the ocean. IMPORTANCE Bacteria and phytoplankton form close associations in the ocean that are driven by the exchange of chemical compounds. The bacterial signal 2-heptyl-4-quinolone (HHQ) slows phytoplankton growth; however, the mechanism responsible remains unknown. Here, we show that HHQ exposure leads to the accumulation of DNA damage in phytoplankton and prevents its repair. While this effect is reversible, HHQ-exposed phytoplankton are also relieved of viral mortality, elevating the ecological consequences of this complex interaction. Further results indicate that HHQ may target phytoplankton proteins involved in nucleotide biosynthesis and DNA repair, both of which are crucial targets for viral success. Our results support microbial cues as emerging players in marine ecosystems, providing a new mechanistic framework for how bacterial communication signals mediate interspecies and interkingdom behaviors. 

   more » « less
3. Bacterial quorum sensing signal arrests phytoplankton cell division and impacts virus-induced mortality

   Scott B. Pollara, Jamie W. (January 2021, mSphere)

   null (Ed.)

   Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems by controlling primary production, structuring marine food webs, mediating carbon export, and influencing global climate. Phytoplankton-bacteria interactions are facilitated by secreted compounds; however, linking these chemical signals, their mechanisms of action, and resultant ecological consequences remains a fundamental challenge. The bacterial quorum sensing signal 2-heptyl-4-quinolone (HHQ), induces immediate, yet reversible, cellular stasis (no cell division nor mortality) in the coccolithophore, Emiliania huxleyi, however, the mechanism responsible remains unknown. Using transcriptomic and proteomic approaches in combination with diagnostic biochemical and fluorescent cell-based assays, we show that HHQ exposure leads to a prolonged S-phase arrest in phytoplankton coincident with the accumulation of DNA damage and lack of repair despite the induction of the DNA damage response (DDR). While this effect is reversible, HHQ-exposed phytoplankton were also protected from viral mortality, ascribing a new role of quorum sensing signals in regulating multi-trophic interactions. Furthermore, our data demonstrate in situ measurements of HHQ coincide with areas of enhanced micro- and nanoplankton biomass. Our results suggest bacterial communication signals as emerging players that may be one of the contributing factors that help structure complex microbial communities throughout the ocean. 

   more » « less
4. Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets

   https://doi.org/10.3390/v13081635  

   Vaidya, Naveen K.; Bloomquist, Angelica; Perelson, Alan S. (August 2021, Viruses)

   null (Ed.)

   The pre-clinical development of antiviral agents involves experimental trials in animals and ferrets as an animal model for the study of SARS-CoV-2. Here, we used mathematical models and experimental data to characterize the within-host infection dynamics of SARS-CoV-2 in ferrets. We also performed a global sensitivity analysis of model parameters impacting the characteristics of the viral infection. We provide estimates of the viral dynamic parameters in ferrets, such as the infection rate, the virus production rate, the infectious virus proportion, the infected cell death rate, the virus clearance rate, as well as other related characteristics, including the basic reproduction number, pre-peak infectious viral growth rate, post-peak infectious viral decay rate, pre-peak infectious viral doubling time, post-peak infectious virus half-life, and the target cell loss in the respiratory tract. These parameters and indices are not significantly different between animals infected with viral strains isolated from the environment and isolated from human hosts, indicating a potential for transmission from fomites. While the infection period in ferrets is relatively short, the similarity observed between our results and previous results in humans supports that ferrets can be an appropriate animal model for SARS-CoV-2 dynamics-related studies, and our estimates provide helpful information for such studies. 

   more » « less
5. Virus infection of phytoplankton increases average molar mass and reduces hygroscopicity of aerosolized organic matter

   https://doi.org/10.1038/s41598-023-33818-4  

   Diaz, Ben P; Gallo, Francesca; Moore, Richard H; Bidle, Kay D (December 2023, Scientific Reports)

   Abstract Viral infection of phytoplankton is a pervasive mechanism of cell death and bloom termination, which leads to the production of dissolved and colloidal organic matter that can be aerosolized into the atmosphere. Earth-observing satellites can track the growth and death of phytoplankton blooms on weekly time scales but the impact of viral infection on the cloud forming potential of associated aerosols is largely unknown. Here, we determine the influence of viral-derived organic matter, purified viruses, and marine hydrogels on the cloud condensation nuclei activity of their aerosolized solutions, compared to organic exudates from healthy phytoplankton. Dissolved organic material derived from exponentially growing and infected cells of well-characterized eukaryotic phytoplankton host-virus systems, including viruses from diatoms, coccolithophores and chlorophytes, was concentrated, desalted, and nebulized to form aerosol particles composed of primarily of organic matter. Aerosols from infected phytoplankton cultures resulted in an increase in critical activation diameter and average molar mass in three out of five combinations evaluated, along with a decrease in organic kappa (hygroscopicity) compared to healthy cultures and seawater controls. The infected samples also displayed evidence of increased surface tension depression at realistic cloud water vapor supersaturations. Amending the samples with xanthan gum to simulate marine hydrogels increased variability in organic kappa and surface tension in aerosols with high organic to salt ratios. Our findings suggest that the pulses of increased dissolved organic matter associated with viral infection in surface waters may increase the molar mass of dissolved organic compounds relative to surface waters occupied by healthy phytoplankton or low phytoplankton biomass. 

   more » « less