Biology subjects

Hernandez, C. A.

Publications and source records attributed to Hernandez, C. A..

6 recordsLinked to original sources

bioRxiv2026

Prophage activity shapes the thermal ecology and evolution of a marine bacterial host

Predicting the response of populations to thermal change is challenging due to temperature-dependent interspecific interactions, such as those between bacteria and their integrated viruses (prophages). Temperature is known to modulate prophage activity, raising the question of whether and how prophages alter host responses to temperature. In this work, we explored how prophage infection shapes host thermal ecology and evolution in a novel marine bacterial isolate carrying a spontaneously inducing prophage. We first characterized the effect of temperature on bacteria and phage population dynamics, finding that high temperatures led to bacterial population crashes and reduced yield, with abundant phage production across all temperatures. To then determine the causal impacts of this phage, we infected a conspecific susceptible strain and found that performance in the novel lysogen was reduced across all temperatures and indistinguishable from the naturally infected strain. Further, we found that evolutionary rescue mutants of the naturally infected strain with an expanded upper thermal limit gained high temperature adaptation through a reduction in prophage activity. Overall, we found that intraspecific variation in thermal ecology was explained by prophage infection, and that adaptation to nonpermissive temperature occurred through modifications to prophage dynamics. This work demonstrates a critical link between viral mobile genetic elements and bacterial thermal responses, and emphasizes the importance of ecological interactions in thermal ecology and evolution.

ecology↗

bioRxiv2026

Mutations in filamentous bacteriophages spark eco-evolutionary feedbacks in Pseudomonas aeruginosa

Microbial populations strongly shape their environment, which can re-route adaptation toward organism-generated fitness optima. However, the conditions that promote these eco-evolutionary feedbacks are unclear. Here, we used experimental evolution to test whether high population density, by strengthening niche construction, drives eco-evolutionary feedbacks in the bacterial pathogen Pseudomonas aeruginosa MPAO1. We then tested for adaptation to organism-modified environments by measuring the relative performance of ancestral and endpoint populations in filtrate generated by each evolutionary line sampled across generations. Contrary to expectations, we found that endpoint populations had higher performance than the ancestral strain in filtrate across nearly all evolutionary lines regardless of population density. This was caused by the emergence of hyperactive filamentous bacterio(phage) mutants during experimental passaging that inhibited the ancestral strain but not endpoint populations in modified media. Hyperactive phages emerged from one of two avirulent prophages in MPAO1s genome (Pf4 or Pf6). Hyperactive phages drove the evolution of phage resistance in bacterial populations via mutations in the type IV pilus (TIVP), the phages binding receptor. In a follow-up experiment, we showed that these TIVP mutations pleiotropically reduced motility and decreased susceptibility to a TIVP-targeting virulent phage, both of which are important traits for P. aeruginosa infection and treatment. Overall, this work suggests that filamentous phage evolution can act as a driver of eco-evolutionary feedbacks in bacterial populations, causing phenotypic and genetic changes that would not be anticipated from adaptation to the extrinsic environment alone.

evolutionary biology↗

bioRxiv2024

Field-evolved resistance to neonicotinoids in the mosquito, Anopheles gambiae, is associated with downregulation and mutations of nicotinic acetylcholine receptor subunits combined with cytochrome P450-mediated detoxification

Neonicotinoid insecticides act selectively on their nicotinic receptor targets leading to variable sensitivity among arthropods. This study aimed to investigate the molecular mechanisms underlying contrasting susceptibility to neonicotinoids observed in wild populations of two mosquito sibling species. Bioassays and a synergism test revealed that the sister taxa, Anopheles gambiae and An. coluzzii, from Yaounde, Cameroon, rely on cytochrome P450s to detoxify neonicotinoids and develop resistance. However, contrary to An. coluzzii, An. gambiae populations are evolving stronger resistance to several active ingredients facilitated by mutations and reduced expression of nicotinic acetylcholine receptors. Six mutations were detected in coding sequences of the {beta}1 and 6 subunits, including two substitutions in one of the loops that modulate ligand binding and sensitivity. Allele frequencies were strongly correlated with a susceptibility gradient between An. coluzzii and An. gambiae suggesting that the mutations may play a key role in sensitivity. Messenger RNA expression levels of the {beta}1, 3, and 7 subunits decreased dramatically, on average by 23.27, 17.50, 15.80-fold, respectively, in wild An. gambiae populations compared to a susceptible insectary colony. By contrast, only the {beta}2 and 9-1 subunits were moderately downregulated (5.28 and 2.67-fold change, respectively) in field-collected An. coluzzii adults relative to susceptible colonized mosquitoes. Our findings provide critical information for the application and resistance management of neonicotinoids in malaria prevention.

molecular biology↗

bioRxiv2022

Hepatocellular carcinoma hosts immature neurons and cholinergic tumors that correlate with adverse molecular features and outcomes

Background & aimsThe unexplained interpatient variation in hepatocellular carcinoma (HCC) remains a major challenge. We aimed at addressing the under-explored association between the disease and the hepatic autonomic nervous system (ANS). Methods & ResultsWe in-depth characterized the innervation of French biobanks HCC samples by conventional biochemistry methods. We also applied bioinformatics approaches to the TCGA dataset in order to stratify samples according to neural features and molecular correlates. We highlighted the predominant parasympathetic polarity of HCC nerves, and demonstrated that a cirrhotic rat model of aggressive HCC hosts liver neurogenesis with cholinergic features. Using the TCGA dataset, we then defined an HCC neural signature, derived from adrenergic and cholinergic receptor levels, that allowed patient stratification into two classes. Cholinergic tumors correlated with TP53 mutations (p [≤] 0.05), shorter progression-free interval (PFI) and overall survival (OS), displayed more pathogenic molecular traits (e.g., AFP-rich, proliferative tumors, mitotic functions including DNA repair, EMT, Ras, and Akt/mTOR pathways), aggressive HCC signatures and B cell accumulation. Instead, adrenergic tumors, predominant in patients aged >60 and with mutated CTNNB1, were correlated with better OS and PFI (p < 0.05), and numerous immune pathways. ConclusionsOur results depict neural features of HCC and how the existing tumor classification may also be shaped by neural inputs. Altogether, we show that the parasympathetic branch of the ANS is implicated in the pathobiology of HCC, and advocate for the use of ANS-targeting drugs in HCC research, many of which are clinically safe and well characterized.

cancer biology↗

bioRxiv2021

Water Stress and Disruption of Mycorrhizae Induce Parallel Shifts in Phyllosphere Microbiome Composition

Water and nutrient limitation are key stressors that affect plant health and ecosystem function. These environmental factors impact both soil- and root-associated microbial communities, and systemically alter plant physiology, but it is less clear how they affect aboveground plant-microbe interactions. Through experimental manipulations in the field and growth chamber, we examined the interacting effects of irrigation, soil fertility, and root mycorrhizal associations on bacterial and fungal communities of the tomato phyllosphere (Solanum lycopersicum). Both water stress and mycorrhizal disruption reduced bacterial richness within plants, homogenized bacterial community diversity among plants, and reduced the relative abundance of dominant fungal taxa. We observed striking parallelism in the individual microbial taxa affected by irrigation and mycorrhizal associations. Given the increasingly understood role of the phyllosphere in shaping plant health and pathogen susceptibility, these results offer an additional mechanism by which belowground conditions shape plant fitness.

ecology↗

bioRxiv2020

Bacteriophage uptake by Eukaryotic cell layers represents a major sink for phages during therapy

For over 100 years, bacteriophages have been known as viruses that infect bacteria. Yet it is becoming increasingly apparent that bacteriophages, or phages for short, have tropisms outside their bacterial hosts. During phage therapy, high doses of phages are directly administered and disseminated throughout the body, facilitating broad interactions with eukaryotic cells. Using live cell imaging across a range of cell lines we demonstrate that cell type plays a major role in phage internalisation and that smaller phages (< 100 nm) are internalised at higher rates. Uptake rates were validated under physiological shear stress conditions using a microfluidic device that mimics the shear stress to which endothelial cells are exposed to in the human body. Phages were found to rapidly adhere to eukaryotic cell layers, with adherent phages being subsequently internalised by macropinocytosis and functional phages accumulating and stably persisting intracellularly. Finally, we incorporate these results into an established pharmacokinetic model demonstrating the potential impact of phage accumulation by these cell layers, which represents a major sink for circulating phages in the body. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.

microbiology↗