Biology subjects

Huerta, C.

Publications and source records attributed to Huerta, C..

5 recordsLinked to original sources

bioRxiv2025

Symbiont virulence is a poor predictor of impacts on host population dynamics

Symbionts are classified as parasites or mutualists based on their impacts on host individuals, but timescale, ecological context, and level of biological organization can all influence symbiosis outcomes, and hence whether they are deemed harmful or beneficial. We designed experiments exposing the key freshwater grazer Daphnia dentifera to two symbionts varying in virulence, to test how well individual-level effects translate into population-level patterns. We found that a seemingly mildly virulent microsporidian strongly reduced host population size, with consequences for primary production, while a yeast that was highly virulent to individuals had no detectable negative effects on host population size. Our experiments show that studies that fail to consider the impacts of symbionts at multiple scales risk focusing mitigation and control measures on the wrong symbionts.

ecology↗

bioRxiv2024

Microsporidian coinfection reduces fitness of a fungal pathogen due to rapid host mortality

Infection outcomes can be strongly context-dependent, shifting a host-symbiont relationship along a parasitism-mutualism continuum. Numerous studies show that under stressful conditions, symbionts that are typically mutualistic can become parasitic. The reverse possibility - a parasite becoming mutualistic - has received much less study. We investigated whether the parasitic microsporidium Ordospora pajunii can become beneficial for its host Daphnia dentifera in the presence of the more virulent fungal pathogen Metschnikowia bicuspidata. We found that, even though infection with O. pajunii reduces the frequency of penetration of M. bicuspidata spores into the host body cavity, it does not improve the survival or reproduction of the host; conversely, coinfection increased the mortality of Daphnia. However, the shorter lifespan of coinfected hosts disrupted the life cycle of M. bicuspidata, greatly reducing its fitness. Thus, coinfection with both pathogens was detrimental to the host at the individual level, but might be beneficial for the host population as a result of greatly reduced production of M. bicuspidata spores. If so, this would mean that O. pajunii outbreaks should delay or prevent M. bicuspidata outbreaks. In support of this, in an analysis of dynamics of naturally occurring outbreaks in two lakes where these pathogens co-occur, we found a time lag in occurrence between O. pajunii and M. bicuspidata, with M. bicuspidata epidemics only occurring after the collapse of O. pajunii epidemics. Thus, these results suggest that the interaction between co-occurring symbionts - and the net impact of a symbiont on a host - might be qualitatively different at different scales. ImportanceUnderstanding the factors that modify infection probability and virulence is crucial for identifying the drivers of infection outbreaks and modeling disease epidemic progression, and increases our ability to control diseases and reduce the harm they cause. One factor that can strongly influence infection probability and virulence is the presence of other pathogens. However, while coexposures and coinfections are incredibly common, we still have only a limited understanding of how pathogen interactions alter infection outcomes, or whether their impacts are scale-dependent. We used a system of one host and two pathogens to show that sequential coinfection can have a tremendous impact on the host and on the infecting pathogens, and that the outcome of (co-)infection can be negative or positive depending on the focal organization level.

ecology↗

bioRxiv2023

Phylogeny, morphology, virulence, ecology, and host range of Ordospora pajunii (Ordosporidae),a microsporidian symbiont of Daphnia spp.

Impacts of microsporidia on host individuals are frequently subtle and can be context dependent. A key example of the latter comes from a recently discovered microsporidian symbiont of Daphnia, the net impact of which was found to shift from negative to positive based on environmental context. Given this, we hypothesized low baseline virulence of the microsporidian; here, we investigated the impact of infection on hosts in controlled conditions and the absence of other stressors. We also investigated its phylogenetic position, ecology and host range. The genetic data indicates that the symbiont is Ordospora pajunii, a newly described microsporidian parasite of Daphnia. We show that O. pajunii infection damages the gut, causing infected epithelial cells to lose microvilli and then rupture. The prevalence of this microsporidian could be high (up to 100% in the lab and 77% of adults in the field). Its overall virulence was low in most cases, but some genotypes suffered reduced survival and/or reproduction. Susceptibility and virulence were strongly host-genotype dependent. We found that North American O. pajunii were able to infect multiple Daphnia species, including the European species D. longispina, as well as Ceriodaphnia spp. Given the low, often undetectable virulence of this microsporidian, and potentially far reaching consequences of infections for the host when interacting with other pathogens or food, this Daphnia - O. pajunii symbiosis emerges as a valuable system for studying the mechanisms of context-dependent shifts between mutualism and parasitism, as well as for understanding how symbionts might alter host interactions with resources. ImportanceThe net outcome of symbiosis depends on the costs and benefits to each partner. Those can be context dependent, driving the potential for an interaction to change between parasitism and mutualism. Understanding the baseline fitness impact in an interaction can help us understand those shifts; for an organism that is generally parasitic, it should be easier for it to become a mutualist if its baseline virulence is relatively low. Recently, a microsporidian was found to become beneficial to its Daphnia hosts in certain ecological contexts, but little was known about the symbiont (including its species identity). Here, we identify it as the microsporidium Ordospora pajunii. Despite the parasitic nature of microsporidia, we found O. pajunii to be, at most, mildly virulent; this helps explain why it can shift towards mutualism in certain ecological contexts and helps establish O. pajunii is a valuable model for investigating shifts along the mutualism-parasitism continuum.

ecology↗

bioRxiv2020

NK cells promote cancer immunoediting through tumor-intrinsic loss of interferon-stimulated gene expression

Natural killer (NK) cells are innate lymphocytes that constantly patrol host tissues against transformed cells in a process known as cancer immunosurveillance. Previous evidence in mice has demonstrated that NK cell-derived IFN-{gamma} can promote immunoevasion by sculpting the immunogenicity of developing tumors in a process known as cancer immunoediting. This process involves the elimination of highly immunogenic "unedited" tumor cells followed by the eventual escape of less immunogenic "edited" tumor cell variants that are able to escape recognition or elimination by the immune system. Here, we show that NK cell-edited fibrosarcomas decrease the expression of 17 conserved IFN-{gamma}-inducible genes compared to unedited tumor cells. High expression of 3 of these identified genes (Psmb8, Trim21, Parp12) in human tumor samples correlates with enhanced survival in breast cancer, melanoma, and sarcoma patients. While NK cell-edited fibrosarcomas displayed resistance to IFN-{gamma} growth suppression in vitro, functional knockouts of individual interferon stimulated genes (ISGs) were not required for outgrowth of unedited tumor cell lines in vitro and in vivo compared to complete loss of IFN signaling. Furthermore, knockout of IFN-{gamma}-intrinsic signaling via deletion of Ifngr in edited B16 F10 and E0771 LMB metastatic cancer cell lines did not impact host survival following lung metastasis. Together, these results suggest that unedited tumors can be selected for decreased IFN-{gamma} signaling to evade immune responses in vivo, and as a consequence, tumor-extrinsic IFN signaling may be more important for potentiating durable anti-tumor responses to advanced solid tumors.

immunology↗

bioRxiv2019

Structural basis of recruitment of RBM39 to DCAF15 by a sulfonamide molecular glue E7820

E7820 and indisulam are two examples of aryl sulfonamides that recruit RBM39 to Rbx-Cul4-DDA1-DDB1-DCAF15 E3 ligase complex, leading to its ubiquitination and degradation by the proteasome. In order to understand their mechanism of action, we carried out kinetic analysis on the recruitment of RBM39 to DCAF15 and solved a crystal structure of DDA1-DDB1-DCAF15 in complex with E7820 and the RRM2 domain of RBM39. E7820 packs in a shallow pocket on the surface of DCAF15 and the resulting modified interface binds RBM39 through the 1 helix of RRM2 domain. Our kinetic studies revealed that aryl sulfonamide and RBM39 bind to DCAF15 in a synergistic manner. The structural and kinetic studies confirm aryl sulfonamides as molecular glues in the recruitment of RBM39 and provide a framework for future efforts to utilize DCAF15 to degrade other protein of interests.

biophysics↗