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High prevalence of multidrug-resistant Salmonella enterica in Thailand food markets: Insights from complete genome and phenotypic characterization of ESBL-producing strains
(2025-12-02) Phaophu P.; Thadtapong N.; Wirth S.E.; Gray A.S.; Dangsuk S.; Ngamwongsatit N.; Aunpad R.; Chaturongakul S.; Phaophu P.; Mahidol University
Salmonella contamination in the food chain is a common root of foodborne outbreaks. The transmission of antimicrobial resistance among Salmonella and food bacteria raises global public health concern. As a major food exporter and travel hub in Southeast Asia, Thailand is particularly susceptible. To better understand the circulating Salmonella, we characterized 74 non-typhoidal Salmonella isolates previously obtained from Thailand food markets. Whole genome sequencing, drug susceptibility testing, and host invasion efficiency assays were performed. The most prevalent serotype was Salmonella serotype Rissen (32.43%) followed by Derby (12.16%). Fifty-two isolates were multidrug-resistant (MDR), with their primary resistance pattern being ampicillin, streptomycin, and tetracycline resistance. The most resistant strain was S. Rissen exhibiting resistance to 13 tested drugs, including third-generation cephalosporin. Six cephalosporin-resistant isolates were identified, four of which were extended-spectrum β-lactamase (ESBL)-producing strains harboring the blaCTX-M-14 or blaCTX-M-55 ESBL gene. Complete genomes showed that three ESBL-producing isolates contained plasmid-mediated ESBL, and the other was chromosomal-mediated. In vitro invasion efficiencies of ESBL-producing strains into mucous-producing human colorectal adenocarcinoma HT29-MTX-E12 cells were compared to the reference strain Salmonella Typhimurium LT2. Statistically significant higher invasion efficiency in the chromosomal-mediated ESBL strain was found. Interestingly, the ESBL plasmid detected during this study was highly similar to a plasmid previously isolated from a Thai patient. This study highlights that the majority of Salmonella isolated from Thai foods are MDR and potentially ESBL-producing strains, highlighting the need for continued surveillance and intervention strategies. IMPORTANCE In Thailand, fermented foods are typically consumed raw, and pork is considered a delicacy of Thai cuisine. The presence of multidrug resistant (MDR) foodborne pathogens in these food types raises concern and presents a risk to public health. Here, we report that Salmonella Rissen was the most prevalent serotype isolated from these food samples in Thailand. All isolates carried virulence gene clusters crucial for pathogenesis, and more than 70% of isolates were MDR strains. Four of the MDR strains were ESBL-producing. Whole genome sequence analysis and phenotypic characterizations revealed that chromosome-mediated ESBL strains possessed higher in vitro invasion efficiency than plasmid-mediated ESBL strains. This study highlights two key public health threats: the risk of acquiring difficult-to-treat MDR Salmonella infections from undercooked food and the circulation of AMR plasmids in fresh markets in Thailand.
The sodium leak channel NALCN in Drd2+ striatal neurons regulates neuronal excitability, locomotion and food-seeking in a sex-dependent manner
(2026-01-01) Castell L.; Naon C.; Rogliardo A.; Ducrocq F.; Makrini L.; Typou A.; Avrillon M.; Mignon A.; Bernat C.; Lory P.; Bertaso F.; Monteil A.; Bosch-Bouju C.; Valjent E.; Castell L.; Mahidol University
The sodium leak channel NALCN is an important modulator of cell excitability. Studies so far demonstrated the critical role of this highly conserved channel in the generation and maintenance of pacemaker activity in cells with spontaneous firing, such as cardiomyocytes, adrenal cells, or neurons. However, the physiological importance of NALCN for neurons with no spontaneous firing has been largely overlooked and remains unknown. Yet, Drd2-expressing striatal projection neurons (SPNs) show an enriched expression of NALCN while they are highly hyperpolarized neurons. Considering that pathogenic variants of NALCN in human result in severe pathological conditions with symptoms that include cognitive and motor impairments, we hypothesized that NALCN in Drd2-SPNs was necessary for their correct signal integration and consequently striatal-associated behaviors. Here, we investigated the impact of NALCN deletion in Drd2-SPNs in both male and female mice. Unexpectedly, we found that only male mice with deletion of NALCN in Drd2-expressing neurons exhibited enhanced locomotor responses to novel environment and reduced motivation in food-seeking tasks, while female mice were unaffected in their behavior. Similarly, electrophysiological recordings of SPNs revealed significant sex differences, with male SPNs lacking NALCN exhibiting altered membrane properties and increased excitability, while females showed only subtle changes. Finally, we found that eticlopride-induced catalepsy and signaling events were differently altered by NALCN deletion in Drd2-SPNs male and female mice. This work constitutes the first evidence that NALCN in Drd2-SPNs participates to striatal function and may be a key modulator of response to antidopaminergic treatments, with significant sex differences.
A Safer Alternative Bio-Repellent: Targeting Mosquito Odorant-Binding Proteins with Catnip-Derived Nepetalactones from Nepeta cataria Leaves
(2026-02-01) Kiatlertpongsa T.; Nonkhwao S.; Charoenrit J.; Saetan J.; Duangprom S.; Songkoomkrong S.; Amonruttanapun P.; Janpan P.; Sobhon P.; Daduang S.; Kornthong N.; Kiatlertpongsa T.; Mahidol University
The reliance on synthetic repellents such as N,N-diethyl-meta-toluamide (DEET) has raised health and environmental concerns, prompting the search for safer, plant-based alternatives. Catnip (Nepeta cataria L.), a rich source of iridoid monoterpenes, particularly nepetalactones, known for strong insect-repellent activity. However, their efficient extraction and molecular mechanisms in insect inhibition remains challenging. This study examined the chemical composition, protein–ligand interactions, and safety profiles of nepetalactones in comparison with DEET, with particular focus on mosquito odorant-binding proteins (OBPs) from Anopheles gambiae (AgamOBP), Culex quinquefasciatus (CquiOBP), and Aedes aegypti (AaegOBP). GC–MS/MS analysis identified nepetalactone isomers as the predominant constituents in catnip extracts obtained via steam distillation and olive oil extraction from dried leaves. Molecular docking results indicated that cis,cis-, cis,trans-, and nepetalactone isomers exhibited higher binding affinities toward the target OBPs than DEET. Furthermore, molecular dynamics simulations confirmed that all nepetalactone–OBP complexes exhibited stable conformations characterized by low average RMSD values and persistent hydrogen bond formation. Notably, cis,trans-NL–AaegOBP, NL–AaegOBP, and cis,cis-NL–AgamOBP complexes displayed lower binding free energies (ΔGMM-PBSA) compared to DEET. These findings suggest that nepetalactones stabilize OBP–ligand interactions while inducing subtle conformational flexibility, potentially disrupting mosquito odorant recognition in a manner distinct from DEET. ADMET predictions indicated that nepetalactones exhibit favorable absorption, distribution, and safety profiles with reduced predicted toxicity compared to DEET. Collectively, these results establish nepetalactones as promising candidates for the development of effective, safe, and sustainable plant-based repellents.
Enhanced induction of fetal hemoglobin by the combination of decitabine with RN-1 in β-thalassemia/HbE erythroid progenitor cells
(2026-12-01) Nualkaew T.; Pongpaksupasin P.; Munkongdee T.; Buasuwan N.; Paiboonsukwong K.; Sripichai O.; Engel J.D.; Hongeng S.; Fucharoen S.; Jearawiriyapaisarn N.; Nualkaew T.; Mahidol University
Background: Fetal hemoglobin (HbF; α2γ2) induction is a well-established approach for β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia. Decitabine, a DNA methyltransferase 1 (DNMT1) inhibitor, has been shown to effectively induce HbF production with a favorable safety profile. However, more potent therapeutic strategies are needed, particularly for β-thalassemia/HbE patients. Methods: We evaluated the HbF-inducing efficacy of ten DNMT1 inhibitors in erythroid progenitor cells derived from β-thalassemia/HbE patients. To further enhance HbF induction, we investigated a combination treatment with decitabine and RN-1, a lysine-specific demethylase 1 (LSD1) inhibitor. HbF expression, cell viability, erythroid differentiation, and proliferation were assessed. Additionally, we investigated the association between treatment response and well-characterized single-nucleotide polymorphisms (SNPs) previously linked to HbF expression. Results: Of the ten DNMT1 inhibitors tested, SGI-110, a dinucleotide analog of decitabine, exhibited similar HbF-inducing efficacy and toxicity profiles as decitabine at equivalent molar dose. The combination treatment with decitabine and RN-1 resulted in a robust additive increase in HbF expression in β-thalassemia/HbE erythroid progenitor cells, albeit with a slight reduction in cell viability. Additionally, the combination treatment improved the delayed differentiation phenotype in β-thalassemia/HbE erythroid cells, accompanied by a reduction in cell proliferation. Interestingly, individual variability in response to RN-1 and the combination treatments was observed, with major responders exhibiting significantly greater increases in HbF compared to minor responders. We identified two SNPs in the BCL11A gene (rs766432 and rs1427407) that were potentially associated with a higher likelihood of major response to treatments. Conclusions: Our findings highlight the potential of targeting two distinct epigenetic corepressors within the γ-globin repressor complex to achieve robust HbF induction. The combination of decitabine and RN-1 represents a promising therapeutic strategy for β-thalassemia, warranting further investigation into the molecular mechanisms underlying individual response variability.
Differentiation of neural stem cells derived from human stem cells from apical papilla into neuronal-like cells undergoing maturation via 3D-neurospheres formation and neurogenic induction
(2026-05-01) Phugdiprapai N.; Leelapattaraphan A.; Vichitvigrom A.; Balit T.; Thongsuk A.; Chodchavanchai T.; Ruangsawasdi N.; White K.L.; Thonabulsombat C.; Songsaad A.T.; Phugdiprapai N.; Mahidol University
Objective: Human stem cells from apical papilla (hSCAPs) are a promising ectomesenchyme‑ derived cell source with neuronal differentiation potential. Under 3D-neurospheres induction, hSCAPs can be induced into neural stem cells (NSCs) and further committed toward neuronal lineages. This study aimed to demonstrate the differentiation of NSCs‑hSCAPs into neuronal‑like cells undergoing maturation through 3D-neurospheres formation and subsequent neurogenic induction. Design: The characterized hSCAPs were induced into NSCs via 3D-neurospheres formation. The intraspheroidal cells were verified for early neural stemness properties and subsequently dissociated and cultured under neurogenic induction conditions for 7 days. Neuronal differentiation was evaluated by identification of Nissl substance, immunofluorescent analysis of neuronal‑associated proteins, quantitative mRNA expression, and depolarization‑evoked intracellular Ca2+ imaging. Results: Following 3D neurosphere induction, hSCAPs formed clusters of intraspheroidal cells exhibiting typical NSCs characteristics, including high expression of Nestin and SOX2 and self‑reaggregation ability. After 7 days of neurogenic induction, the differentiated cells displayed distinct neuronal‑like morphologies, reduced expression of early neuronal markers (Nestin/NES and SOX2/SOX2), and increased expression of early neuronal differentiation-associated markers (Beta‑III tubulin/TUBB3) at both protein and mRNA levels. The synaptic vesicle‑associated gene (SV2A) was highly detected at the mRNA level. Furthermore, depolarization‑evoked Ca2+ responses after KCl stimulation were observed, indicating membrane excitability and voltage‑gated calcium channel in the differentiated cells. Conclusions: NSCs‑hSCAPs possess the capacity to generate neuronal‑like cells undergoing maturation via 3D-neurospheres formation and neurogenic induction.