Biology subjects

Hudson, A. O.

Publications and source records attributed to Hudson, A. O..

10 recordsLinked to original sources

bioRxiv2024

Unraveling the Genetic Complexity of Invasive Lonicera spp.: Evidence of Hybridization from Nuclear and Chloroplast Genome Analysis

Members of the Lonicera genus, commonly known as honeysuckles, encompass both native and invasive species in North America, the latter posing significant ecological challenges. Invasive honeysuckles can disrupt native ecosystems by outcompeting local flora, altering habitats, and affecting wildlife populations. Effective management and control of these species are critical but hindered by the difficulty of accurate identification due to overlapping morphological traits. Traditional control measures recommended by government agencies, such as cutting, burning, and chemical treatments, have proven only partially effective, sometimes complicated by misidentification of species. The morphological identification of invasive honeysuckles is notoriously challenging. Key distinguishing features are often subtle, variable, and sometimes only discernible during specific developmental stages, complicating field identification efforts. This taxonomic ambiguity underscores the urgent need for more precise identification methods that transcend conventional morphological assessments. In this study, we explore the molecular identity of a Lonicera isolate collected from the Finger Lakes region of Western New York. Through detailed genetic analysis, we demonstrate that the specimen likely possesses maternal inheritance from Lonicera tatarica while the majority of its nuclear genome is associated with Lonicera insulara. Both species are prevalent in the region and known for their invasive potential. Our findings highlight the utility of molecular techniques as a complementary tool for species identification within the Lonicera genus. By providing a clearer genetic framework for distinguishing between morphologically similar species, this approach can enhance conservation strategies, inform management decisions, and improve ecological restoration efforts. As invasive species continue to threaten biodiversity, integrating molecular diagnostics with traditional methods offers a promising path toward more effective environmental stewardship.

ecology↗

bioRxiv2024

Whole-Genome Sequencing of a Janthinobacterium sp. Isolated from the Patagonian Desert

Janthinobacterium is a genus of Gram-negative environmental bacteria that survive extreme conditions by forming biofilms and producing pigments. Janthinobacterium sp. LS2A, an extremophile isolated from soil in the Chilean Patagonia, contains seven known biosynthetic gene clusters, including the purple pigment violacein, which may aid in its survival in harsh environments.

genomics↗

bioRxiv2023

Genetic drift and genome reduction in the plant pathogen Candidatus Liberibacter solanacearum shapes a new enzyme in lysine biosynthesis.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid--a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the effects of genome reduction and genetic drift on the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyses the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased [~]2-fold in the insect host compared to in planta. CLsoDHDPS has increased aggregation propensity, implying mutations have destabilised the enzyme but are compensated for through elevated chaperone expression and a stabilised oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study reveals the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary association. We suggest that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.

evolutionary biology↗

bioRxiv2021

Constrained evolutionary paths to macrolide resistance in a Neisseria commensal converge on ribosomal genes through sequence duplication

Neisseria commensals are an indisputable source of resistance for their pathogenic relatives; however, the evolutionary paths commensal species take to reduced susceptibility in this genus have been relatively underexplored. Here, we leverage in vitro selection as a powerful screen to identify the genetic adaptations that produce azithromycin resistance ([≤] 2 g/mL) in the Neisseria commensal, N. elongata. Across multiple lineages (n=7/16), we find mutations encoding resistance converge on the gene encoding the 50S ribosomal L34 protein (rpmH) and the intergenic region proximal to the 30S ribosomal S3 protein (rpsC) through duplication events. Importantly, one of the laboratory evolved mutations in rpmH is identical, and two nearly identical, to those recently reported to confer high-level resistance to azithromycin in N. gonorrhoeae. Transformations into the ancestral N. elongata lineage confirmed the causality of both rpmH and rpsC mutations. Though most lineages inheriting duplications suffered in vitro fitness costs, one variant showed no growth defect, suggesting the possibility that it may be sustained in natural populations. Finally, we assessed the potential of horizontal transfer of derived resistance mutations into multiple strains of N. gonorrhoeae. Though we were unable to transform N. gonorrhoeae in this case, studies like this will be critical for predicting commensal alleles that are at risk of rapid dissemination into pathogen populations. ImportanceCommensal bacterial populations have been increasingly recognized for their importance as sources of resistance for pathogens, however the collection of antimicrobial resistance (AMR) mechanisms within these communities are often understudied. The risk of reduced antibiotic susceptibility as a result of horizontal gene transfer (HGT) is amplified in highly recombinogenic genera, such as the Neisseria. Indeed, there have been multiple documented cases of macrolide and beta-lactam resistance acquisition in the pathogen N. gonorrhoeae from close commensal relatives. This work uncovers multiple novel azithromycin resistance-conferring mutations in a Neisseria commensal through experimental evolution, investigates their fitness impacts, and explores the possibility of transfer to N. gonorrhoeae. Ultimately these types of studies will illuminate those resistance mutations that may rapidly be acquired across species boundaries.

microbiology↗

bioRxiv2020

A comparative survey of betacoronavirus strain molecular dynamics identifies key ACE2 binding sites

Comparative functional analysis of the dynamic interactions between various Betacoronavirus mutant strains and broadly utilized target proteins such as ACE2 and CD26, is crucial for a more complete understanding of zoonotic spillovers of viruses that cause diseases such as COVID-19. Here, we employ machine learning to replicated sets of nanosecond scale GPU accelerated molecular dynamics simulations to statistically compare and classify atom motions of these target proteins in both the presence and absence of different endemic and emergent strains of the viral receptor binding domain (RBD) of the S spike glycoprotein. Machine learning was used to identify functional binding dynamics that are evolutionarily conserved from bat CoV-HKU4 to human endemic/emergent strains. Conserved dynamics regions of ACE2 involve both the N-terminal helices, as well as a region of more transient dynamics encompassing K353, Q325 and a novel motif AAQPFLL 386-92 that appears to coordinate their dynamic interactions with the viral RBD at N501. We also demonstrate that the functional evolution of Betacoronavirus zoonotic spillovers involving ACE2 interaction dynamics are likely pre-adapted from two precise and stable binding sites involving the viral bat progenitor strains interaction with CD26 at SAMLI 291-5 and SS 333-334. Our analyses further indicate that the human endemic strains hCoV-HKU1 and hCoV-OC43 have evolved more stable N-terminal helix interactions through enhancement of an interfacing loop region on the viral RBD, whereas the highly transmissible SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1) have evolved more stable viral binding via more focused interactions between the viral N501 and ACE2 K353 alone.

biophysics↗

bioRxiv2020

Exploration of the Neisseria resistome reveals resistance mechanisms in commensals that may be acquired by N. gonorrhoeae through horizontal gene transfer

Non-pathogenic Neisseria have repeatedly been demonstrated to transfer antibiotic resistance genes to their pathogenic relative, Neisseria gonorrhoeae. However, the resistance genotypes and subsequent phenotypes of non-pathogens within the genus have been studied and described less frequently. Here, we use Etests to characterize the minimum inhibitory concentrations (MICs) of a panel of Neisseria (n=26) - including several commensal species - acquired from the CDC & FDAs Antibiotic Resistance (AR) Isolate Bank to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database (CARD) Resistance Gene Identifier (RGI) platform to predict possible causal resistance-encoding mutations. Within this panel, resistant isolates to all tested antimicrobials including penicillin (n=5/26), ceftriaxone (n=2/26), cefixime (n=3/26), tetracycline (n=10/26), azithromycin (n=11/26), and ciprofloxacin (n=4/26) were found. In total we identify 63 distinct mutations predicted by RGI to be involved in resistance. The presence of several of these mutations had clear associations with increases in MIC such as: DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type {beta}-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by non-pathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.

microbiology↗

bioRxiv2020

Function and evolution of B-Raf loop dynamics relevant to cancer recurrence under drug inhibition

Oncogenic mutations in the kinase domain of the B-Raf protein have long been associated with cancers involving the MAPK pathway. One constitutive MAPK activating mutation in B-Raf, the V600E (valine to glutamate) replacement occurring adjacent to a site of threonine phosphorylation (T599) occurs in many types of cancer, and in a large percentage of certain cancers, such as melanoma. Because ATP binding activity and the V600E mutation are both known to alter the physical behavior of the activation loop in the B-Raf ATP binding domain, this system is especially amenable to comparative analyses of molecular dynamics simulations modeling various genetic and drug class variants. Here, we employ machine learning enabled identification of functionally conserved protein dynamics to compare how the binding interactions of four B-Raf inhibitors impact the functional loop dynamics controlling ATP activation. We demonstrate that drug development targeting B-Raf has progressively moved towards ATP competitive inhibitors that demonstrate less tendency to mimic the functionally conserved dynamic changes associated with ATP activation and leading to the side effect of hyperactivation (i.e. inducing MAPK activation in non-tumorous cells in the absence of secondary mutation). We compare the functional dynamic impacts of V600E and other sensitizing and drug resistance causing mutations in the regulatory loops of B-Raf, confirming sites of low mutational tolerance in these regions. Lastly, we investigate V600E sensitivity of B-Raf loop dynamics in an evolutionary context, demonstrating that while sensitivity has an ancient origin with primitive eukaryotes, it was also secondarily increased during early jawed vertebrate evolution.

biophysics↗

bioRxiv2019

Whole-genome sequencing of five proteobacteria isolated from Lechuguilla Cave, New Mexico, USA: Insights into taxonomy and quorum-sensing

Genomic resources remain scarce for bacteria isolated from oligotrophic caves. We sequenced the genomes of five Proteobacteria isolated from Lechuguilla Cave in New Mexico, USA. Genome-based phylogeny indicates that each strain belongs to a distinct genus. Two Rhizobiaceae isolates possess the genomic potential for the biosynthesis of acyl-homoserine lactone.

genomics↗

bioRxiv2019

Insight into the resistome and quorum sensing system of a divergent Acinetobacter pittii isolate from an untouched site of the Lechuguilla Cave

Acinetobacter are Gram-negative bacteria belonging to the sub-phyla Gammaproteobacteria, commonly associated with soils, animal feeds and water. Some members of the Acinetobacter have been implicated in hospital-acquired infections, with broad-spectrum antibiotic resistance. Here we report the whole genome sequence of LC510, an Acinetobacter species isolated from deep within a pristine location of the Lechuguilla Cave. Pairwise nucleotide comparison to three type strains within the genus Acinetobacter assigned LC510 as an Acinetobacter pittii isolate. Scanning of the LC510 genome identified two genes coding for {beta}-lactamase resistance, despite the fact that LC510 was isolated from a portion of the cave not previously visited by humans and protected from anthropogenic input. The ability to produce acyl-homoserine lactone (AHL) signal in culture medium, an observation that is consistent with the identification of the luxI and luxR homologs in its genome, suggests that cell-to-cell communication remains important in an isolated cave ecosystem.

microbiology↗

bioRxiv2019

The gene annotated by the locus tag At3g08860 encodes a β-alanine/L-alanine aminotransferase in Arabidopsis thaliana

The aminotransferase gene family in the model plant Arabidopsis thaliana consists of 44 genes some of which remain uncharacterized. This study elucidates the function of an uninvestigated aminotransferase annotated by the locus tag At3g08860. The cDNA was shown to functionally complement two E. coli mutants auxotrophic for the amino acids {beta}-alanine (non-proteogenic) and L-alanine (proteogenic). The elucidation of At3g08860 activity has the potential to facilitate experiments for the optimization of plant lines involved in nitrogen utilization efficiency, response to hypoxia, osmo-protection, vitamin B5 and coenzyme A metabolism.

plant biology↗