Biology subjects

Tan, H. S.

Publications and source records attributed to Tan, H. S..

7 recordsLinked to original sources

bioRxiv2026

Chromosomal breakage in Arabidopsis thaliana neo-polyploids occurs preferentially at candidate fragile sites colocalized with ancient genome rearrangements

Newly formed polyploids often suffer extensive aneuploidy and chromosome rearrangement. We explored whether these are predictable and conserved across genotypes. We quantified whole-chromosome and segmental aneuploidy in progeny arrays of neo-polyploid Arabidopsis thaliana from two accessions (Col-0 and Ler). 29% of progeny had whole-chromosome and/or segmental aneuploidies. Strikingly, segmental aneuploidy arose exclusively from Ler, preferentially maternally, showing that genotype and sex of origin matter. Breakpoints of segmental aneuploidies were non-random, with over 2/3 mapping to five potentially fragile regions (PFRs). Two PFRs overlap with junctions of ancient chromosomal fusions that differentiate the A. thaliana genome from that of its relatives and also overlap more broadly with hotspots of recurrent chromosomal rearrangements differentiating species in the Brassicaceae family. Several PFRs overlap with large tandemly repeated disease resistance gene clusters. Our results support the hypothesis of a link between ancestral genome rearrangements and present-day chromosome fragility. Polyploidy serving as a context that makes aneuploidies more likely to arise and survive, with fragile sites lending a degree of predictability.

genomics↗

bioRxiv2024

Pangenome and Transcriptomic Analysis Revealed Distinct Virulence Genes Profiles and Infection Responses in Shigella Sonnei and Shigella Flexneri

Shigellosis, a major cause of diarrheal death, is predominantly caused by Shigella flexneri and Shigella sonnei. Notably, S. sonnei has begun to overtake S. flexneri in incidence worldwide. We conducted a comparative pangenome and transcriptomic analysis of these two species using the well-established model Caenorhabditis elegans as an infection model to explore this shift. Pangenome analysis of 46 S. sonnei and 111 S. flexneri strains revealed that S. sonnei has more core genes (44%) than S. flexneri (13.6%). Additionally, S. sonnei, but not S. flexneri, has core virulence genes. The transcriptomic study during C. elegans infection showed that S. sonnei significantly upregulates the ferric enterobactin outer membrane transporter (fepA) and other metabolic processes (sulfur, thiamine and arginine). In contrast, S. flexneri upregulates regulatory genes involved in biofilm formation, transcription, cellular processes, and cell communication. These findings suggest that S. sonneis ability to upregulate specific genes, including fepA, may confer a competitive advantage over S. flexneri. These findings provide a comprehensive understanding of the genetic and functional adaptations that may contribute to the global epidemiological shift from S. flexneri to S. sonnei, underscoring the need for further research into the mechanisms driving S. sonneis increased virulence and adaptability.

microbiology↗

bioRxiv2024

Transcriptomic Insights into the Virulence of Acinetobacter baumannii During Infection: Role of Iron Uptake and Siderophore Production Genes

Acinetobacter baumannii is a top-priority pathogen as classified by the World Health Organisation. It causes life-threatening infections in immunocompromised patients, resulting in prolonged hospitalisation and high mortality. Increasing cases of community-acquired A. baumannii infections with rapid progression and severe infections have been reported. This study used the previously described Galleria mellonella infection model to investigate the virulence mechanisms of the community strain C98 (Ab-C98) via transcriptomic analysis using direct RNA sequencing. This strain showed greater killing and more rapid colonisation in the larvae than a clinical reference strain (ATCC BAA1605). Differential gene expression analysis revealed the significant upregulation of three major iron clusters: the acinetobactin and baumannoferrin clusters for siderophore production and the Feo system for ferrous iron uptake. Targeted knockout of siderophore production genes (basC, bfnD and isochorismatase family protein) significantly attenuated virulence in mutants with minimal impact on the bacterial growth in vivo. Overall, this study highlights the virulence of basC, isochorismatase family protein and bfnD in the pathogenicity of A. baumannii. As these targets are highly conserved in A. baumannii and the closely related A. pittii and A. lactucae, they could serve as potential therapeutic targets for developing new antivirulence agents to combat these pathogens.

microbiology↗

bioRxiv2024

Exploring the Impact of Probiotic Route of Administration on Its Protective Effects against Pathogenic Infection in Galleria mellonella

In probiotic research, identifying promising candidates for further development remains challenging. Traditional mammalian models are invaluable for assessing efficacy, but limitations such as high cost, ethical considerations, and lengthy reproductive cycles can slow the preliminary screening process. The Galleria mellonella larvae have emerged as a powerful in vivo-like screening model. Most studies on G. mellonella often use intra-hemocelic injection, bypassing the natural gut entry point for probiotics, which is analogous to introducing probiotics into the mammalian blood. Despite their advantages, discrepancies exist between G. mellonella and mammalian models, particularly regarding the route of probiotic administration. This study bridges this gap by investigating the differential effects of oral and intra-hemocelic administration of a probiotic, Escherichia coli Nissle 1917 (EcN1917), on its protective efficacy against a gastrointestinal pathogen, Salmonella Typhimurium ATCC 14028 (ST14028). The larvae were challenged with varying doses of EcN1917 and ST14028 through both routes. Survivability, health index, and bacterial burden in the gut and hemolymph were assessed. This study demonstrated that oral EcN1917 pre-treatment significantly increased survivability against ST14028 infection compared to the control group and alleviated the pathogen gut burden. Notably, injection pre-treatment decreased survivability. This discrepancy is attributed to the dual nature of probiotics, exhibiting beneficial effects in the gut but acting as pathogens in non-native locations like the hemolymph. This study concludes that the route of probiotic administration in G. mellonella significantly impacts the protective effects of probiotics.

microbiology↗

bioRxiv2020

A fluoroquinolone-sensitive Shigella sonnei UKMCC1015 downregulates the expression of ribosomal proteins in response to sub-lethal concentration of norfloxacin

1.Shigella causes shigellosis that requires antibiotic treatment in severe cases. Sub-lethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unknown. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a norfloxacin-sensitive strain, Shigella sonnei UKMCC1015. Firstly, the whole genome of S. sonnei UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. However, transcriptomic analysis showed that low NOR levels do not change the expression of AMR genes and norfloxacin targets. Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated ppGpp levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase (relA). However, high levels of ppGpp (due to relA overexpression) are detrimental to the continued survival of S. sonnei during prolonged exposure to NOR. This study revealed that a norfloxacin-sensitive strain responds differently to sub-lethal NOR than commonly reported in resistant strains. Overexpression of relA (high ppGpp levels) may reduce the mutability of S. sonnei UKMCC1015 in response to NOR exposure and affect NOR tolerance.

microbiology↗

bioRxiv2020

Fourier spectral density of the coronavirus genome

We present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values which vary inversely with the genome size generally. It exhibits no other peaks apart from those associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density.

bioinformatics↗

bioRxiv2019

Disease and phenotype relevant genetic variants identified from histone acetylomes in human hearts

Identifying genetic markers for heterogeneous complex diseases such as heart failure has been challenging, and may require prohibitively large cohort sizes in genome-wide association studies (GWAS) in order to demonstrate statistical significance1. On the other hand, chromatin quantitative trait loci (QTL), elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritising variants for disease-association. Here, we captured non-coding genetic variants by performing enhancer H3K27ac ChIP-seq in 70 human control and end-stage failing hearts, mapping out a comprehensive catalogue of 47,321 putative human heart enhancers. 3,897 differential acetylation peaks (FDR < 0.05) pointed to recognizable pathways altered in heart failure (HF). To identify cardiac histone acetylation QTLs (haQTLs), we regressed out confounding factors including HF disease status, and employed the G-SCI test2 to call out 1,680 haQTLs (FDR < 0.1). A subset of these showed significant association to gene expression, either in cis (180), or through long range interactions (81), identified by Hi-C and Hi-ChIP performed on a subset of hearts. Furthermore, a concordant relationship was found between the gain or disruption of specific transcription factor (TF) binding motifs, inferred from alternative alleles at the haQTLs, associated with altered H3K27ac peak heights. Finally, colocalisation of our haQTLs with heart-related GWAS datasets allowed us to identify 62 unique loci. Disease-association for these new loci may indeed be mediated through modification of H3K27-acetylation enrichment and their corresponding gene expression differences.

genomics↗