Background: The increasing rate of antimicrobial-resistantNeisseria gonorrhoeaeposes a considerable public health threat due to the difficulty in treating gonococcal infections. This study examined antimicrobial resistance (AMR) to drugs recommended for gonorrhea treatment between 2015 and 2017, and the AMR determinants and genetic compositions of plasmids in 3 gonococcal strains with high-level penicillin resistance.Methods: We collected 117N.gonorrhoeaeisolates from patients with gonococcal infections who attended Siriraj Hospital, Bangkok, Thailand, between 2015 and 2017. Minimum inhibitory concentrations (MICs) of penicillin, tetracycline, ciprofloxacin, azithromycin, spectinomycin, cefixime, and ceftriaxone were determined by the agar dilution method. PCR amplification and sequencing of 23S rRNA andmtrR(a negative regulator of MtrCDE efflux pump) were performed. Whole genomes of 3 PPNG strains with high-level penicillin resistance (MIC ≥ 128 μg/ml) were sequenced using Illumina and Nanopore sequencing platforms.Results: The proportions ofN.gonorrhoeaeisolates with resistance were 84.6% for penicillin, 91.5% for tetracycline, and 96.6% for ciprofloxacin. All isolates were susceptible to spectinomycin, azithromycin, cefixime, and ceftriaxone. An adenine deletion within a 13 bp inverted repeat sequence in themtrRpromoter and an H105Y mutation in themtrRcoding region were found in theN.gonorrhoeaeisolate with the highest azithromycin MIC value (1 μg/ml). Three high-level penicillin-resistant isolates contained nonmosaic type IIpenAand had mutations inpenBand themtrRcoding region. All isolates with high-level penicillin resistance carried the conjugative plasmids with or without the Dutch typetetMdeterminant, the beta-lactamase plasmid (Rio/Toronto), and the cryptic plasmid.Conclusions: The gonococcal population in Thailand showed high susceptibility to ceftriaxone and azithromycin, current dual therapy recommended for gonorrhea treatment. As elevated MIC of azithromycin has been observed in 1 strain ofN.gonorrhoeae, expanded and enhanced surveillance of antimicrobial susceptibility and study of genetic resistance determinants are essential to improve treatment guidelines.

This study investigated the genetic diversity, antimicrobial resistance profiles, and virulence characteristics of Acinetobacter non-baumannii isolates obtained from four hospitals in southern Thailand. Clinical data, genome information, and average nucleotide identity (ANI) were analyzed for eight isolates, revealing diverse genetic profiles and novel sequence types (STs). Minimum spanning tree analysis indicated potential clonal spread of certain STs across different geographic regions. Antimicrobial resistance genes (ARGs) were detected in all isolates, with a high prevalence of genes conferring resistance to carbapenems, highlighting the challenge of antimicrobial resistance in Acinetobacter spp. infections. Mobile genetic elements (MGEs) carrying ARGs were also identified, emphasizing the role of horizontal gene transfer in spreading resistance. Evaluation of virulence-associated genes revealed a diverse range of virulence factors, including those related to biofilm formation and antibiotic resistance. However, no direct correlation was found between virulence-associated genes in Acinetobacter spp. and specific clinical outcomes, such as infection severity or patient mortality. This complexity suggests that factors beyond gene presence may influence disease progression and outcomes. This study emphasizes the importance of continued surveillance and molecular epidemiological studies to combat the spread of multidrug-resistant (MDR) Acinetobacter non-baumannii strains. The findings provide valuable insights into the epidemiology and genetic characteristics of this bacteria in southern Thailand, with implications for infection control and antimicrobial management efforts.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced-stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced-stage WTs, of which 7 cases were chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in advanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemotherapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profiles of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Chronic myeloid leukemia (CML) is a hematologic malignancy originating from hematopoietic stem cells and driven by the BCR-ABL fusion oncogene. Imatinib (IM), a tyrosine kinase inhibitor, is commonly used as a frontline therapy for CML. However, some patients exhibit primary resistance or show persistent molecular evidence of disease despite treatment. Emerging studies indicate that exosome-derived microRNAs (miRNAs) play a role in mediating drug resistance and may serve as promising biomarkers for cancer diagnosis and predicting therapeutic response. This study aimed to investigate the plasma exosomal miRNA expression profiles in CML patients to identify potential biomarkers associated with IM resistance. Exosomes were isolated from plasma samples of both IM-sensitive and IM-resistant CML patients. The exosomal miRNA content was analyzed using RNA sequencing, followed by differential expression analysis, which revealed 13 upregulated and 21 downregulated miRNAs in IM-resistant patients. Subsequent bioinformatics analysis indicated significant enrichment in pathways related to autophagy and PI3K-Akt signaling. Notably, miR-451a and miR-16–2-3p were among the most significantly upregulated miRNAs in exosomes from IM-resistant individuals. Interestingly, miR-16–2-3p expression showed a strong inverse correlation with clinical laboratory results, specifically blood urea nitrogen and creatinine levels. This pilot study identified plasma exosomal miRNAs, particularly miR-451a and miR-16–2-3p, as potential biomarkers for imatinib resistance in chronic myeloid leukemia. Target gene prediction was performed to explore their regulatory roles. Despite the limited sample size, these findings enhance our understanding of drug resistance mechanisms and warrant further validation in larger cohorts to assess their clinical relevance and therapeutic potential.

Penicillinase-producing Neisseria gonorrhoeae (PPNG) possessing bla_TEM-135 is a serious public health threat. With only a single change in amino acid sequence, bla_TEM-135 could evolve into TEM-type extended-spectrum beta-lactamase (ESBL), which hydrolyzes extended-spectrum cephalosporins, including ceftriaxone and cefixime. We investigated the molecular epidemiological characteristics, types of plasmids of PPNG isolates, and prevalence of PPNG clinical isolates producing TEM-135 beta-lactamases. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was used to determine the molecular epidemiological characteristics of 99 PPNG isolates collected from 2015 to 2017. A mismatch amplification mutation assay examined the bla_TEM-135 gene prevalence. Of 89 NG-MAST sequence types identified, 65 (73.0%) were novel. Only 17.7% (43/243) of the PPNG isolates belonged to 16 genogroups. The most frequent plasmid was African, followed by Rio/Toronto and Asian. The bla_TEM-135 allele was in Rio/Toronto plasmids. The bla_TEM-135 allele was present in 23.2% (23/99) of PPNG isolates. PPNG isolates expressing TEM-135 beta-lactamase exhibited significantly higher penicillin MIC values than TEM-1 PPNG isolates. PPNG isolates showed high genetic diversity and high proportions of bla_TEM-135 alleles. Mutation of the bla_TEM-135 allele is worrisome: only 1 mutation could see TEM-1 evolve into an ESBL variant degrading ceftriaxone. Ongoing surveillance of bla_TEM-135 and new PPNG isolate variants is imperative.