Biology subjects

Ausubel, F. M.

Publications and source records attributed to Ausubel, F. M..

6 recordsLinked to original sources

bioRxiv2026

Lysosome-related organelle genes are required for mitochondrial transformations during bacterial infections in Caenorhabditis elegans.

Detecting and responding to pathogenic bacteria is an essential function of eukaryotic cells. As bacteria-derived organelles, mitochondria carry lipids, proteins, and other molecules such as iron which are required for bacterial growth, and thus are subject to pathogenic bacterial attack. In fact, mitochondrial morphology and function are often altered during early bacterial infection. However, the mechanism by which bacterial pathogen attack triggers mitochondrial responses is unknown. Here, we demonstrate that infection by the pathogenic bacterium Staphylococcus aureus or Pseudomonas aeruginosa or hypoxia leads to remodeling of the mitochondrial network in the host Caenorhabditis elegans. Our analysis discovers that lysosome-related organelle (LRO) genes are required for this remodeling and indicates that LROs also precipitate downstream infection-response gene expression.

immunology↗

bioRxiv2022

Chaotic signatures in host-microbe interactions

Host-microbe interactions constitute dynamical systems that can be represented by mathematical formulations that determine their dynamic nature, and are categorized as deterministic, stochastic, or chaotic. Knowing the type of dynamical interaction is essential for understanding the system under study. Very little experimental work has been done to determine the dynamical characteristics of host-microbe interactions and its study poses significant challenges. The most straightforward experimental outcome involves an observation of time to death upon infection. However, in measuring this outcome, the internal parameters, and the dynamics of each particular host-microbe interaction in a population of interactions are hidden from the experimentalist. To investigate whether a time-to-death (time to event) dataset provides adequate information for searching for chaotic signatures, we first determined our ability to detect chaos in simulated data sets of time-to-event measurements and successfully distinguished the time-to-event distribution of a chaotic process from a comparable stochastic one. To do so, we introduced an inversion measure to test for a chaotic signature in time-to-event distributions. Next, we searched for chaos, in time-to-death of Caenorhabditis elegans and Drosophila melanogaster infected with Pseudomonas aeruginosa or Pseudomonas entomophila, respectively. We found suggestions of chaotic signatures in both systems, but caution that our results are preliminary and highlight the need for more fine-grained and larger data sets in determining dynamical characteristics. If validated, chaos in host-microbe interactions would have important implications for the occurrence and outcome of infectious diseases, the reproducibility of experiments in the field of microbial pathogenesis and the prediction of microbial threats. ImportanceIs microbial pathogenesis a predictable scientific field? At a time when we are dealing with Coronavirus Disease 2019 (COVID-19) there is intense interest in knowing about the epidemic potential of other microbial threats and new emerging infectious diseases. To know whether microbial pathogenesis will ever be a predictable scientific field requires knowing whether a host-microbe interaction follows deterministic, stochastic, or chaotic dynamics. If randomness and chaos are absent from virulence, there is the hope for prediction in the future regarding the outcome of microbe-host interactions. Chaotic systems are inherently unpredictable although it is possible to generate shortterm probabilistic models, as is done in applications of stochastic processes and machine learning to weather forecasting. Information on the dynamics of a system is also essential for understanding the reproducibility of experiments, a topic of great concern in biological sciences. Our study finds preliminary evidence for chaotic dynamics in infectious diseases.

microbiology↗

bioRxiv2021

A screen for mutants deficient in coronatine-mediated suppression of root immunity identifies Arabidopsis SDA1 as a novel integrator of immunity and phytohormone signaling

Despite the importance of the root immune system in the interaction with rhizosphere microbes, the majority of genetic screens for immunity regulators have been performed in leaves. A previous screen identified 27 hsm (hormone-mediated suppression of MAMP-triggered immunity) mutants that are impaired in jasmonic acid (JA)-mediated suppression of pattern-triggered immunity (PTI) in roots. Here we characterized 16 of the hsm mutants that retain JA sensitivity and are potential negative regulators of root immunity. We found that the majority of hsm mutants show enhanced resistance to Fusarium, a root fungal pathogen; however, only a subset are more resistant to a foliar pathogen. Surprisingly, 12 of 16 hsm mutants are also impaired in abscisic acid (ABA)-mediated suppression of PTI, suggesting a largely shared pathway between JA- and ABA-mediated immune suppression in roots. Although all hsm mutants are insensitive to JA-mediated suppression of root immunity, hsm4 shows hypersensitivity to JA-mediated root growth inhibition and JA-induced gene expression. Consistently, hsm4 is more resistant to leaf pathogens, suggesting that HSM4 is a negative regulator of both root and leaf immunity. Hsm4 was mapped to a mutation in a conserved ARM-repeat protein homologous to yeast SDA1, which has been reported to regulate 60S ribosome biogenesis. As translational reprogramming is a critical layer of immune regulation, this work suggests that AtSDA1 is a novel negative translational regulator of immunity. Additionally, a comprehensive characterization of all 16 hsm mutants provides a genetic toolkit to identify novel mechanisms that regulate root immunity.

plant biology↗

bioRxiv2021

Natural variation in Arabidopsis ISR1 affects iron localization and induced systemic resistance

Beneficial root-associated bacteria can induce systemic resistance (ISR) to foliar pathogens and there is known transcriptional and genetic overlap in the root response to iron deficiency and ISR. A previous study found that there is natural variation in ISR among Arabidopsis accessions. The Ws accession is deficient in ISR, and the responsible recessive genetic locus, named ISR1, was mapped to chromosome 3. To find candidate genes that may underlie ISR deficiency in Ws, we identified genes that are induced in response to the ISR-triggering bacterium Pseudomonas simiae WCS417 and to iron stress and that have non-synonymous mutations in the Ws genome with respect to the ISR-responsive Col-0. We identified a kelch-domain containing protein encoded by At3g07720 that has a genomic rearrangement in Ws. We found that overexpression of Col-0 At3g07720 restores ISR to Ws, indicating that At3g07720 encodes ISR1. Isr1 loss of function mutants do not affect plant growth under iron limiting conditions but have increased levels of apoplastic iron. We found that iron supplementation, P. simiae WCS417, or a loss of isr1 enhance ROS production in a non-additive manner, suggesting they work through the same mechanism to enhance resistance. Our findings show that ISR1 is required for iron localization, immunity, and ISR, and suggest that increased iron uptake induced by ISR-eliciting bacteria may directly contribute to immunity through increased reactive oxygen production.

plant biology↗

bioRxiv2019

The Pseudomonas aeruginosa accessory genome elements, including bacterial immune systems effect virulence towards C. elegans

Multicellular animals and bacteria frequently engage in predator-prey and host-pathogen interactions, such as the well-studied relationship between Pseudomonas aeruginosa and the nematode Caenorhabditis elegans. This study investigates the genomic and genetic basis of bacterial-driven variability in P. aeruginosa virulence towards C. elegans. Natural isolates of P. aeruginosa that exhibit diverse genomes display a broad range of virulence towards C. elegans. Using gene association and genetic analysis, we identified accessory genome elements that correlate with virulence, including both known and novel virulence determinants. Among the novel genes, we found a viral-like mobile element, the teg block, that impairs virulence and whose acquisition is restricted by CRISPR-Cas systems. Further genetic and genomic evidence suggests that spacer-targeted elements preferentially associate with lower virulence and suggest a positive, albeit indirect, role for host CRISPR-Cas systems in the restriction of accessory genome elements that may be detrimental to virulence.

evolutionary biology↗

bioRxiv2017

RhlR, but not RhlI, allows P. aeruginosa bacteria to evade Drosophila Tep4- mediated opsonization

When Drosophila flies feed on Pseudomonas aeruginosa strain PA14, some bacteria cross the intestinal barrier and start proliferating inside the hemocoel. This process is limited by hemocytes through phagocytosis. We have previously shown that the PA14 quorum-sensing regulator RhlR is required for these bacteria to elude the cellular immune response. RhlI synthesizes the auto-inducer signal that activates RhlR. Here, we compare the null mutant phenotypes of rhlR and rhlI in a variety of infection assays in Drosophila and in the nematode Caenorhabditis elegans. Surprisingly, in Drosophila, unlike{Delta} rhlR mutants,{Delta} rhlI mutants are only modestly attenuated for virulence and are poorly phagocytosed and opsonized in a Thioester-containing Protein4-dependent manner. Likewise, {Delta}rhlI but not {Delta}rhlR mutants colonize the digestive tract of C. elegans and kill it as efficiently as wild-type PA14. Thus, RhlR has an RhlI-independent function in eluding detection or counter-acting the action of the immune system. In contrast to the intestinal infection model, Tep4 mutant flies are more resistant to PA14 in a septic injury model, which also depends on rhlR. Thus, the Tep4 putative opsonin can either be protective or detrimental to host defense depending on the infection route.

immunology↗