Biology subjects

Qiu, W.

Publications and source records attributed to Qiu, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

TinA enables kinesin-14/KlpA to exhibit processive minus-end-directed motility

Kinesin-14 motors contribute to spindle assembly by localizing to spindle poles and anchoring the minus ends of spindle microtubules. Unlike other kinesin-14 motors, KlpA uniquely exhibits plus-end-directed motility on single microtubules as individual homodimers. However, the mechanism by which KlpA achieves minus-end-directed motility on single microtubules remains elusive. Here, we report that TinA, a highly conserved microtubule-anchoring protein, serves as an activator of KlpA for minus-end-directed motility. TinA directly interacts with KlpA to form minus-end-directed complexes that exhibit continuous movement on microtubules with two distinct velocity modes. The assembly of KlpA-TinA complexes depends on TinA binding to the central stalk of KlpA. Furthermore, TinA is a microtubule-binding protein, with its C-terminal region playing a critical role in microtubule interaction. Deletion of the C-terminus of TinA markedly reduces its microtubule-binding ability and severely impairs the formation of KlpA-TinA complexes. Nonetheless, KlpA-TinA complexes formed without the C-terminus of TinA still exhibit minus-end-directed motility, albeit with a single velocity mode. Collectively, these findings provide critical mechanistic insights into how TinA modulates KlpA, enabling the kinesin-14 motor to achieve minus-end-directed motility.

biophysics↗

bioRxiv2024

Data Release: High-Resolution Imaging and Segmentation of P7 Mouse Tissue Microarchitecture Using FIB-SEM and Machine Learning

This report presents a comprehensive data release exploring the tissue microarchitecture of P7 aged mice using Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) combined with machine learning-based segmentations of nuclei. The study includes high-resolution 3D volumes and nucleus segmentations for seven vital tissues--pancreas, liver, kidney, heart, thymus, hippocampus, and skin--from a single mouse. The detailed datasets are openly accessible onOpenOrganelle.org, providing a valuable resource for the scientific community to support further research and collaboration.

cell biology↗

bioRxiv2024

A telosma mosaic virus-based vector for foreign gene expression and virus-induced gene silencing in the perennial woody vine, passion fruit (Passiflora edulis)

Passion fruit (Passiflora edulis) is a perennial, woody, tropical vine crop. It produces edible round to oval fruit that has been increasingly favored for its unique aroma and taste, and richness in antioxidants, vitamins and minerals. However, the functional genomic study of passion fruit lags far behind due to a lack of simple and efficient genetic tools. Here, we report the development of virus-mediated protein overexpression (VOX) and virus-induced gene silencing (VIGS) vector based on telosma mosaic virus (TelMV), an emerging potyvirus infecting passion fruit plants worldwide. This vector, designated pTelMV-GW, incorporates the Gateway-compatible recombination sites for rapid gene cloning. We show that this vector allows for the systemic stable expression of two heterologous proteins, green fluorescent protein (GFP) and bacterial phytoene synthase (crtB) in passion fruit plants, and pTelMV-GW containing different fragments of GFP can also induce systemic gene silencing on the GFP-transgenic N. benthamiana plants. Moreover, we demonstrated that in passion fruit plants, this vector can trigger gene silencing of endogenous phytoene desaturase (PDS) to a limited extent. Furthermore, we upgraded the vector by using a mild TelMV strain that does not induce noticeable symptoms in plants. We show that the upgraded vector (pTelMV-R181K-GW) containing PDS or ChlI fragments induces the robust silencing of the corresponding endogenous gene in passion fruit plants. Together, we reported the first development of VIGS and VOX vectors in passion fruit plants, as the first step in our endeavor to discover horticulturally important genes for improving passion fruit production and quality.

plant biology↗

bioRxiv2024

Promoted Read-through and Mutation Against Pseudouridine-CMC by an Evolved Reverse Transcriptase

Pseudouridine ({Psi}) is an abundant RNA chemical modification that can play critical roles in the biological functions of RNA, and RNA-therapeutic applications. Current {Psi} detection methods are limited in identifying {Psi}s at base-resolution in U-rich sequence contexts, where {Psi} occurs frequently. The N-cyclohexyl N-(2-morpholinoethyl)carbodiimide (CMC) can selectively label {Psi} in RNA by forming the CMC-{Psi} adduct. Here we report that an evolved reverse transcriptase ("RT-1306") shows promoted read-through and mutation against the CMC-{Psi}. The mutation signature can resolve the occurrence of {Psi}s within UU-containing sequences. We developed "Mut-{Psi}-seq" utilizing CMC and RT-1306 for transcriptome-wide mapping of {Psi} at base-resolution. The mutation signatures robustly identify reported {Psi}s in human rRNAs via the ROC analysis, and elongated CMC reaction duration increases the detection sensitivity of {Psi}. We report a high-confidence list of {Psi} sites in polyA-enriched RNAs from HEK-293T cells identified by orthogonal chemical treatments (CMC and bisulfite). The mutation signatures resolve the position of {Psi} in UU-containing sequences, revealing diverse occurrence of {Psi}s in such sequences. This work provides new methods and datasets for biological research of {Psi}, and demonstrates the potential of combining the reverse transcriptase engineering and selective chemical labeling to expand the toolkit for RNA chemical modifications studies.

biochemistry↗

bioRxiv2024

How does the ion concentration affect the functions of kinesin BimC

BimC family proteins are bipolar motor proteins belonging to the kinesin superfamily which promote mitosis by crosslinking and sliding apart antiparallel microtubules. Understanding the binding mechanism between the kinesin and the microtubule is crucial for researchers to make advances in the treatment of cancer and other malignancies. Experimental research has shown that the ion concentration affects the function of BimC significantly. But the insights of the ion-dependent function of BimC remain unclear. By combining molecular dynamics (MD) simulations with a series of computational approaches, we studied the electrostatic interactions at the binding interfaces of BimC and the microtubule under different KCl concentrations. We found the electrostatic interaction between BimC and microtubule is stronger at 0 mM KCl compared to 150 mM KCl, which is consistent with experimental conclusions. Furthermore, important salt bridges and residues at the binding interfaces of the complex were identified, which illustrates the details of the BimC-microtubule interactions. Molecular dynamics analyses of salt bridges identified that the important residues on the binding interface of BimC are positively charged, while those residues on the binding interface of the tubulin heterodimer are negatively charged. The finding in this work reveals some important mechanisms of kinesin-microtubule binding, which helps the future drug design for cancer therapy.

biophysics↗

bioRxiv2024

Connectome-driven neural inventory of a complete visual system

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brains volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the flys visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the [~]53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

neuroscience↗

bioRxiv2024

A deep profile of gene expression across 18 human cancers

Clinically and biologically valuable information may reside untapped in large cancer gene expression data sets. Deep unsupervised learning has the potential to extract this information with unprecedented efficacy but has thus far been hampered by a lack of biological interpretability and robustness. Here, we present DeepProfile, a comprehensive framework that addresses current challenges in applying unsupervised deep learning to gene expression profiles. We use DeepProfile to learn low-dimensional latent spaces for 18 human cancers from 50,211 transcriptomes. DeepProfile outperforms existing dimensionality reduction methods with respect to biological interpretability. Using DeepProfile interpretability methods, we show that genes that are universally important in defining the latent spaces across all cancer types control immune cell activation, while cancer type-specific genes and pathways define molecular disease subtypes. By linking DeepProfile latent variables to secondary tumor characteristics, we discover that tumor mutation burden is closely associated with the expression of cell cycle-related genes. DNA mismatch repair and MHC class II antigen presentation pathway expression, on the other hand, are consistently associated with patient survival. We validate these results through Kaplan-Meier analyses and nominate tumor-associated macrophages as an important source of survival-correlated MHC class II transcripts. Our results illustrate the power of unsupervised deep learning for discovery of cancer biology from existing gene expression data.

bioinformatics↗

bioRxiv2024

A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO CHROMATIN

The influence of the metastasis promoting proteins mutant p53 (mtp53) and MDM2 on Cancer Persistent Repair (CPR) to promote cancer cell survival is understudied. Interactions between the DNA repair choice protein 53BP1 and wild type tumor suppressor protein p53 (wtp53) regulates cell cycle control. Cancer cells often express elevated levels of transcriptionally inactive missense mutant p53 (mtp53) that interacts with MDM2 and MDM4/MDMX (herein called MDMX). The ability of mtp53 to maintain a 53BP1 interaction while in the context of interactions with MDM2 and MDMX has not been described. We asked if MDM2 regulates chromatin-based phosphorylation events in the context of mtp53 by comparing the chromatin of T47D breast cancer cells with and without MDM2 in a phospho-peptide stable isotope labeling in cell culture (SILAC) screen. We found reduced phospho-53BP1 chromatin association, which we confirmed by chromatin fractionation and immunofluorescence in multiple breast cancer cell lines. We used the Proximity Ligation Assay (PLA) in breast cancer cell lines and detected 53BP1 in close proximity to mtp53, MDM2, and the DNA repair protein MDC1. Through disruption of the mtp53-MDM2 interaction, by either Nutlin 3a or a mtp53 R273H C-terminal deletion, we uncovered that mtp53 was required for MDM2-53BP1 interaction foci. Our data suggests that mtp53 works with MDM2 and 53BP1 to promote CPR and cell survival.

cancer biology↗

bioRxiv2024

IOBR2: Multidimensional Decoding Tumor Microenvironment for Immuno-Oncology Research

The use of large transcriptome datasets has greatly improved our understanding of the tumor microenvironment (TME) and helped develop precise immunotherapies. The increasing popularity of multi-omics sequencing, single-cell transcriptome sequencing (scRNA), and spatial transcriptome sequencing has led to numerous new discoveries. However, these findings require clinical phenotypic validation with a large sample size. To enhance the integration of multi-omics in advancing research on the tumor microenvironment, we have developed a systematic and comprehensive analytical tool (Immuno-Oncology Biological Research 2, IOBR2) based on our prior work. IOBR2 offers six modules for TME analysis based on multi-omics data. These modules cover data preprocessing, TME estimation, TME infiltrating patterns, cellular interactions, genome and TME interaction, and visualization for TME relevant features, as well as modelling based on key features. IOBR2 integrates multiple vital microenvironmental analysis algorithms and signature estimation methods, simplifying the analysis and downstream visualization of the TME. In addition to providing a quick and easy way to construct gene signatures from single-cell data, IOBR2 also provides a way to construct a reference matrix for TME deconvolution from single-cell RNAseq. The analysis pipeline and feature visualization are user-friendly and provide a comprehensive description of the complex TME, offering insights into tumor-immune interactions. A comprehensive gitbook (https://iobr.github.io/book/) is available with a user-friendly manual and complete analysis workflow for each module.

cancer biology↗

bioRxiv2023

Vagus nerve stimulation by focused ultrasound attenuates acute myocardial ischemia/reperfusion injury predominantly through cholinergic anti-inflammatory pathway

BackgroundThe invasive method using electrically stimulating vagus nerve has been demonstrated to inhibit the inflammatory response against acute myocardial ischemia/reperfusion(I/R) injury. This neuro-regulatory technique used is invasive implantation of electrical stimulators which have the risk of infection and other complications. A non-invasive method of vagus nerve stimulation applying on acute myocardial I/R injury is particularly important and desirable. ObjectivesThis study aimed to test the hypothesis that focused ultrasound stimulation(FUS) of vagus nerve attenuates acute myocardial I/R injury through cholinergic anti-inflammatory pathway. MethodsThis study was completed with two parts. In the first part, ischemia was induced by left anterior descending coronary artery (LAD) occlusion for 30 minutes (min), followed by 2 hours (h) of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Infammatory markers, arrhythmia score, histopathology, infammatory markers 7 nicotinic acetylcholine receptor (7nAchR) protein were determined. In the second part, ischemia was induced by LAD occlusion for 30 min, followed by 24h of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Myocardial fibrosis, infarct size, echocardiographic measurements, biomarkers of pro-oxidative stress, antioxidant and myocardial apoptosis were determined. ResultsFUS of vagus nerve significantly decreased the level of infammatory markers in I/R+FUS group compared with the I/R group, I/R+vagotomy group and I/R+vagotomy+FUS group. FUS decreased the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF), while also reduced arrhythmia score in I/R+FUS group compared with the I/R group. These improvements were associated with the inhibition of acute inflammatory reaction through cholinergic anti-inflammatory pathway. FUS limited myocardial fibrosis and infarct size, preserved left ventricular function. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. ConclusionsThe noninvasive method of ultrasonic neuromodulation using FUS of vagus nerve exerted protective effects on acute myocardial I/R injury. Its potential mechanisms involved the suppression of acute inflammatory reaction through cholinergic anti-inflammatory pathway.

neuroscience↗

bioRxiv2023

Familiarity training enhance straightening of neural trajectory for video prediction

Predictive processing in the visual system is pivotal for efficient sensory-driven behaviors. Previous research has shown that the visual system transforms sequential inputs into straighter temporal trajectories. However, the specific role of neural straightening in predictive processing, especially in how learning reshapes this phenomenon for enhanced prediction, remains unclear. To address this, we analyzed V2 population activity in macaques during familiarity training with video stimuli. Our findings reveal that repeated exposure to the same movies significantly enhances neural straightening, indicating a critical role of learning in refining neural trajectories for prediction. In parallel, our studies with the deep predictive network model, Pred-Net, demonstrated similar enhancements in neural straightening in response to familiar movies. This underscores a strong association between neural straightening and predictive coding. Together, our results provide novel insights into the adaptive mechanisms of the visual cortex, enriching our understanding of how learning shapes neural path-ways for efficient prediction.

neuroscience↗

bioRxiv2023

Isolating structured salient variations in single-cell transcriptomic data with StrastiveVI

Single-cell RNA sequencing (scRNA-seq) has provided deeper insights into biological processes by highlighting differences at the cellular level. Within these single-cell omics measurements, researchers are often interested in identifying variations associated with a specific covariate. For instance, in aging research, it becomes vital to differentiate variations related to aging. To address this, we introduce StrastiveVI (Structured Contrastive Variational Inference; https://github.com/suinleelab/StrastiveVI), which effectively separates the variations of interest from other dominant biological signals in scRNA-seq datasets. When deployed on aging and Alzheimers disease (AD) datasets, StrastiveVI efficiently isolates aging and AD-associated patterns, distinguishing them from dominant variations linked to sex, tissue, and cell type that are unrelated to aging or AD. In doing so, it underscores both well-known genes and potential novel genes related to aging or AD.

bioinformatics↗

bioRxiv2023

Kinesin-14 HSET and KlpA are non-processive microtubule motors with load-dependent power strokes

Accurate chromosome segregation during cell division relies on coordinated actions of microtubule (MT)-based motor proteins in the mitotic spindle. Kinesin-14 motors play vital roles in spindle assembly and maintenance by crosslinking antiparallel MTs at the spindle midzone and anchoring spindle MTs minus ends at the poles. We investigate the force generation and motility of the Kinesin-14 motors HSET and KlpA, revealing that both motors function as non-processive motors under load, producing single power strokes per MT encounter. Each homodimeric motor generates forces of [~]0.5 pN, but when assembled in teams, they cooperate to generate forces of 1 pN or more. Importantly, cooperative activity among multiple motors leads to increased MT-sliding velocities. Our findings deepen our understanding of the structure-function relationship of Kinesin-14 motors and underscore the significance of cooperative behavior in their cellular functions.

biophysics↗

bioRxiv2023

Circulating exosomes from Alzheimer's disease suppress VE-cadherin expression and induce barrier dysfunction in recipient brain microvascular endothelial cell

BackgroundBlood-brain barrier (BBB) breakdown is a component of the progression and pathology of Alzheimers disease (AD). BBB dysfunction is primarily caused by reduced or disorganized tight junction or adherens junction proteins of brain microvascular endothelial cell (BMEC). While there is growing evidence of tight junction disruption in BMECs in AD, the functional role of adherens junctions during BBB dysfunction in AD remains unknown. Exosomes secreted from senescent cells have unique characteristics and contribute to modulating the phenotype of recipient cells. However, it remains unknown if and how these exosomes cause BMEC dysfunction in AD. ObjectivesThis study aimed to investigate the potential roles of AD circulating exosomes and their RNA cargos in brain endothelial dysfunction in AD. MethodsWe isolated exosomes from sera of five cases of AD compared with age- and sex-matched cognitively normal controls using size-exclusion chromatography technology. We validated the qualities and particle sizes of isolated exosomes with nanoparticle tracking analysis and atomic force microscopy. We measured the biomechanical natures of the endothelial barrier of BMECs, the lateral binding forces between live BMECs, using fluidic force miscopy. We visualized the paracellular expressions of the key adherens junction protein VE-cadherin in BMEC cultures and a 3D BBB model that employs primary human BMECs and pericytes with immunostaining and evaluated them using confocal microscopy. We also examined the VE-cadherin signal in brain tissues from five cases of AD and five age- and sex-matched cognitively normal controls. ResultsWe found that circulating exosomes from AD patients suppress the paracellular expression levels of VE-cadherin and impair the barrier function of recipient BMECs. Immunostaining analysis showed that AD circulating exosomes damage VE-cadherin integrity in a 3D model of microvascular tubule formation. We found that circulating exosomes in AD weaken the BBB depending on the RNA cargos. In parallel, we observed that microvascular VE-cadherin expression is diminished in AD brains compared to normal controls. ConclusionUsing in vitro and ex vivo models, our study illustrates that circulating exosomes from AD patients play a significant role in mediating the damage effect on adherens junction of recipient BMEC of the BBB in an exosomal RNA-dependent manner. This suggests a novel mechanism of peripheral senescent exosomes for AD risk.

neuroscience↗

bioRxiv2022

A Synthetic Stress-relaxing Photoresin for Ultrafast Volumetric Bioprinting

Tomographic volumetric bioprinting (VBP) enables fast photofabrication of cell-laden hydrogel constructs in one step, addressing the limitations of conventional layer-by-layer additive manufacturing. However, existing biomaterials that fulfill the physicochemical requirements of VBP are limited to gelatin-based photoresins of high polymer concentrations. The printed microenvironments are predominantly static and stiff, lacking sufficient capacity to support 3D cell growth. We here report a dynamic resin based on thiol-ene photo-clickable polyvinyl alcohol (PVA) and thermo-sensitive sacrificial gelatin for fast VBP of functional ultrasoft cell-laden hydrogel constructs within 7-15 seconds. Using gelatin allows VBP of permissive hydrogels with low PVA contents of 1.5%, providing a stress-relaxing environment for fast cell spreading, 3D osteogenic differentiation of embedded human mesenchymal stem cells and matrix mineralization. Additionally, site-specific immobilization of molecules-of-interest inside a PVA hydrogel is achieved by 4D tomographic thiol-ene photopatterning. This technique may enable spatiotemporal control of cell-material interactions and guided in vitro tissue formation using programmed cell-friendly light. Altogether, this study introduces a synthetic dynamic photoresin enabling fast VBP of functional ultrasoft hydrogel constructs with well-defined physicochemical properties and high efficiency.

bioengineering↗

bioRxiv2022

Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures

Cold-chain environment could extend the survival duration of SARS-CoV-2 and increases the risk of transmission. However, the effect of clod-chain environmental factors and packaging materials on SARS-CoV-2 stability and the efficacy of intervention measures to inactivate SARS-CoV-2 under cold-chain environment remains uncertain. This study aimed to unravel cold-chain environmental factors that preserved the stability of SARS-CoV-2 and disinfection measures against SARS-CoV-2 under the cold-chain environment. The spike gene of SARS-CoV-2 isolated from Wuhan hu-1 was used to construct the SARS-CoV-2 pseudovirus and used as model of the SARS-CoV-2 virus. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, various types of packaging material surfaces i.e., PE plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of LED visible light(wavelength 450 nm-780 nm) and airflow movement on the stability of SARS-CoV-2 pseudovirus at -18{degrees} C were subsequently assessed. The results show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surface compared with the non-porous surfaces including PE plastic, stainless steel and Teflon. Compared with 25{degrees} C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperature. Seawater preserved viral stability both at -18{degrees} C and repeated freeze-thawing cycles compared with deionized water. LED visible light illumination and airflow movement environment at -18{degrees} C reduced the SARS-CoV-2 pseudovirus stability. In conclusion, our results indicate cold-chain temperature and seawater as risk factors for SARS-CoV-2 transmission and LED visible light illumination and airflow movement as possible disinfection measures of SARS-CoV-2 under the cold-chain environment. ImportanceIt is widely recognized that low temperature is a condition for maintaining virus vitality, and cold-chain transportation spreads the events of the SARS-CoV-2 were reported. This study provides that the decay rate of the SARS-CoV-2 pseudovirus at low temperatures varies on different packaging materials, and salt ions present in frozen foods such as seafood may protect virus survival. These results provide evidence for the possibility of SARS-CoV-2 transmission through cold-chain transport and also suggest the importance for disinfection of items. However, the commonly used disinfection methods of ultraviolet radiation and chemical reagents are generally not suitable for the disinfection of frozen food. Our study shows LED visible light illumination and airflow movement as possible disinfection measures of SARS-CoV-2 under the cold-chain environment. This has implications for reducing the long-distance transmission of the virus through cold-chain transportation.

microbiology↗

bioRxiv2022

Detection of Borrelia garinii in the USA

Borrelia garinii, is a cause of Lyme disease in Europe and Asia. For the first time, we report it in the southeastern United States in rodents. Whole genome sequencing and phylogenetic analysis revealed that USA-located B. garinii is part of a clade consisting primarily of few European and majority of Far Eastern strains. Continued surveillance of wildlife hosts and ticks is necessary to assess the ecological status and public health risks of B. garinii in southeastern US.

microbiology↗

bioRxiv2022

Development of recombinant monoclonal antibodies targeting conserved VlsE epitopes in Lyme disease pathogens

VlsE (variable major protein-like sequence, expressed) is an outer surface protein of the Lyme disease pathogen (Borreliella species) and a key diagnostic biomarker of Lyme disease. However, the high sequence variability of VlsE poses a challenge to the development of consistent VlsE-based diagnostics and therapeutics. In addition, the standard diagnostic protocols detect immunoglobins elicited by the Lyme pathogen, not the presence of pathogen or its derived antigens. Here we describe the development of recombinant monoclonal antibodies (rMAbs) that bind specifically to conserved epitopes on VlsE. We first quantified amino-acid sequence variability encoded by the vls genes from thirteen B. burgdorferi genomes by evolutionary analyses. We showed broad inconsistencies of the sequence phylogeny with the genome phylogeny, indicating rapid gene duplications, losses, and recombination at the vls locus. To identify conserved epitopes, we synthesized peptides representing five long conserved invariant regions (IRs) on VlsE. We tested the antigenicity of these five IR peptides using sera from three mammalian host species including human patients, the natural reservoir white-footed mouse (Peromyscus leucopus), and VlsE-immunized New Zealand rabbits (Oryctolagus cuniculus). The IR4 and IR6 peptides emerged as the most antigenic and reacted strongly with both the human and rabbit sera, while all IR peptides reacted poorly with sera from natural hosts. Four rMAbs binding specifically to the IR4 and IR6 peptides were identified, cloned, and purified. Given their specific recognition of the conserved epitopes on VlsE, these IR-specific rMAbs are promising diagnostic and theragnostic agents for direct detection of Lyme disease pathogens regardless of strain heterogeneity.

microbiology↗