Coinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a patient with MDR-TB and HIV coinfection who survived for over 8 years, despite poor treatment adherence and comorbidities. Whole genome sequencing (WGS) of the infecting () strain revealed a unique genomic deletion, spanning 18 genes, including key genes involved in hypoxia response, intracellular survival, immunodominant antigens, and dormancy.
View Article and Find Full Text PDFBacteria adapt to their host by mutating specific genes and by reprogramming their gene expression. Different strains of a bacterial species often mutate the same genes during infection, demonstrating convergent genetic adaptation. However, there is limited evidence for convergent adaptation at the transcriptional level.
View Article and Find Full Text PDFIntramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable "sterilizing immunity" at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization.
View Article and Find Full Text PDFWithin-host adaptation is a hallmark of chronic bacterial infections, involving substantial genomic changes. Recent large-scale genomic data from prolonged infections allow the examination of adaptive strategies employed by different pathogens and open the door to investigate whether they converge toward similar strategies. Here, we compiled extensive data of whole-genome sequences of bacterial isolates belonging to miscellaneous species sampled at sequential time points during clinical infections.
View Article and Find Full Text PDFMucinous colorectal carcinomas (MC) constitute 10% of colorectal malignancies. Recently, an increased risk of colorectal cancer has been demonstrated in germline mutation carriers. Furthermore, germline mutation carriers have exhibited a higher-than-expected frequency of MC tumors.
View Article and Find Full Text PDFBacterial small RNAs (sRNAs) are posttranscriptional regulators of gene expression that base pair with complementary sequences on target mRNAs, often in association with the chaperone Hfq. Here, using experimentally identified sRNA-target pairs, along with gene expression measurements, we assess basic principles of regulation by sRNAs. We show that the sRNA sequence dictates the target repertoire, as point mutations in the sRNA shift the target set correspondingly.
View Article and Find Full Text PDFWe have previously described the existence of membranous nanotubes, bridging adjacent bacteria, facilitating intercellular trafficking of nutrients, cytoplasmic proteins, and even plasmids, yet components enabling their biogenesis remain elusive. Here we reveal the identity of a molecular apparatus providing a platform for nanotube biogenesis. Using Bacillus subtilis (Bs), we demonstrate that conserved components of the flagellar export apparatus (FliO, FliP, FliQ, FliR, FlhB, and FlhA), designated CORE, dually serve for flagellum and nanotube assembly.
View Article and Find Full Text PDFSmall RNAs (sRNAs) associated with the RNA chaperon protein Hfq are key posttranscriptional regulators of gene expression in bacteria. Deciphering the sRNA-target interactome is an essential step toward understanding the roles of sRNAs in the cellular networks. We developed a broadly applicable methodology termed RIL-seq (RNA interaction by ligation and sequencing), which integrates experimental and computational tools for in vivo transcriptome-wide identification of interactions involving Hfq-associated sRNAs.
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