Biology subjects

Love, M. S.

Publications and source records attributed to Love, M. S..

4 recordsLinked to original sources

bioRxiv2025

Prevalence of the parasitic copepod, Sarcotaces sp., infection in British Columbia rockfishes (Sebastes sp.) and implications for rockfish life-history

Marine fishes often suffer detrimental effects of parasitism, which can affect multiple life-history traits, such as maturity, growth, fecundity, and mortality. Rockfishes (genus Sebastes), in the northeast Pacific Ocean, are commonly parasitized by copepods in the genus Sarcotaces. These copepods form large cysts within the body cavity, or in the musculature of individuals. There is a lack of baseline data on the prevalence of Sarcotaces sp. infection and the effect of infection on rockfish health and life-history. Here, we present data on Sarcotaces sp. infection in 23 rockfish species (including two thornyhead species, genus Sebastolobus) that includes over 37,000 individual records collected on Fisheries and Oceans Canadas (Pacific Region) groundfish research surveys. Sarcotaces sp. were found in all geographic areas covered by the surveys (the coastal waters of British Columbia), and at all depths fish were encountered. Infection rates in the various species ranged from 0% to 10%, and were highest for Pacific Ocean Perch (POP), Silvergray, Rougheye/Blackspotted Complex (REBS), Yellowmouth, and Yelloweye rockfishes. We found that Sarcotaces sp. infection shifted the length-at-maturity ogive, with infected individuals maturing at larger sizes--particularly for males, who exhibited a 22.3 mm increase (95% CrI [credible interval]: 5.5, 39.8) in length-at-maturity across species. For most species, this effect was greater in males than in females, and the effect was most pronounced in POP, Silvergray, and REBS rockfish. Moreover, we found that immature males were 2.5 times more likely to be infected than mature males (95% CrI: 1.3, 4.7) and immature females were 1.7 times more likely to be infected than mature females (95% CrI: 0.9, 3.0). While speculative, this is consistent with Sarcotaces sp. infection acting as a co-morbidity, possibly affecting fish health and the probability of perishing before reaching maturity. Body condition was largely unrelated to infection status; however, a slight increase ({approx} 5%) in condition was associated with infection in REBS, Yelloweye, and Yellowmouth rockfishes. To our knowledge, this is the first large-scale report on Sarcotaces sp. infection within rockfishes and on rockfish life-history traits. Future work is needed to elucidate how infection influences other life-history traits and, importantly, whether these changes affect key stock assessment parameters and, ultimately, catch advice provided to fisheries managers.

ecology↗

bioRxiv2023

Cryptosporidium Life Cycle Small Molecule Probing Implicates Translational Repression And An Apetala 2 Transcription Factor In Sexual Differentiation

The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans, Cryptosporidium spp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate sexual differentiation and maturation. mRNA-seq studies confirmed selective modulation of sexual differentiation for 10 hit compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompanies Cryptosporidium sexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in sexual differentiation. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for gamont formation.

microbiology↗

bioRxiv2021

Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis

There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo. Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3, 5-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required for cholesterol metabolism. Finally, in this work the pharmacokinetic properties of Rv1625c agonists are optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a novel role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies. Author SummaryThe recalcitrance of Mycobacterium tuberculosis (Mtb) to conventional antibiotics has created a need to identify novel pharmacological mechanisms to inhibit Mtb pathogenesis. There is a growing understanding of the metabolic adaptations Mtb adopts during infection to support its survival and pathogenesis. This has generated interest in identifying small molecule compounds that effectively inhibit these in vivo metabolic adaptations, while overcoming challenges like poor pharmacokinetic properties or redundancy in target pathways. The Mtb cholesterol utilization pathway has repeatedly been speculated to be a desirable antibiotic target, but compounds that successfully inhibit this complex pathway and are suitable for use in vivo are lacking. Here, we establish that stimulating cAMP synthesis in Mtb is a mechanism that is sufficient to block cholesterol utilization by the bacterium, preventing the release of key metabolic intermediates that are derived from breakdown of the cholesterol molecule. For the first time, we identify small molecule agonists of the Mtb adenylyl cyclase Rv1625c that have promising pharmacological properties and are suitable for use during in vivo studies. These Rv1625c agonists increase cAMP synthesis, inhibit cholesterol utilization by Mtb, and disrupt Mtb pathogenesis in mouse models of chronic infection.

microbiology↗

bioRxiv2021

Defining the Yeast Resistome through in vitro Evolution and Whole Genome Sequencing

In vitro evolution and whole genome analysis were used to comprehensively identify the genetic determinants of chemical resistance in the model microbe, Saccharomyces cerevisiae. Analysis of 355 curated, laboratory-evolved clones, resistant to 80 different compounds, demonstrates differences in the types of mutations that are identified in selected versus neutral evolution and reveals numerous new, compound-target interactions. Through enrichment analysis we further identify a set of 137 genes strongly associated with or conferring drug resistance as indicated by CRISPR-Cas9 engineering. The set of 25 most frequently mutated genes was enriched for transcription factors and for almost 25 percent of the compounds, resistance was mediated by one of 100 independently derived, gain-of-function, single nucleotide variants found in 170-amino-acid domains in two Zn2C6 transcription factors, YRR1 and YRM1 (p < 1x 10 -100). This remarkable enrichment for transcription factors as drug resistance genes may explain why it is challenging to develop effective antifungal killing agents and highlights their important role in evolution.

genetics↗