Gata2 haploinsufficiency promotes proliferation and functional decline of hematopoietic stem cells with myeloid bias during aging.

During aging, hematopoietic stem cell (HSC) function wanes with important biological and clinical implications for benign and malignant hematology, and other comorbidities, such as cardiovascular disease. However, the molecular mechanisms regulating HSC aging remain incompletely defined. GATA2 haploinsufficiency driven clinical syndromes initially result in primary immunodeficiencies and routinely evolve into hematologic malignancies on acquisition of further epigenetic mutations in both young and older patients. Using a conditional mouse model of Gata2 haploinsufficiency, we discover that during aging Gata2 promotes HSC proliferation, monocytosis, and loss of the common lymphoid progenitor. Aging of Gata2 haploinsufficient mice also offsets enhanced HSC apoptosis and decreased granulocyte-macrophage progenitor number normally observed in young Gata2 haploinsufficient mice. Transplantation of elderly Gata2 haploinsufficient HSCs impairs HSC function with evidence of myeloid bias. Our data demonstrate that Gata2 regulates HSC aging and suggest the mechanisms by which Gata2 mediated HSC aging has an impact on the evolution of malignancies in GATA2 haploinsufficiency syndromes.

A role for arthropods as vectors of multidrug-resistant Enterobacterales in surgical site infections from South Asia.

Understanding how multidrug-resistant Enterobacterales (MDRE) are transmitted in low- and middle-income countries (LMICs) is critical for implementing robust policies to curb the increasing burden of antimicrobial resistance (AMR). Here, we analysed samples from surgical site infections (SSIs), hospital surfaces (HSs) and arthropods (summer and winter 2016) to investigate the incidence and transmission of MDRE in a public hospital in Pakistan. We investigated Enterobacterales containing resistance genes (blaCTX-M-15, blaNDM and blaOXA-48-like) for identification, antimicrobial susceptibility testing and whole-genome sequencing. Genotypes, phylogenetic relationships and transmission events for isolates from different sources were investigated using single-nucleotide polymorphism (SNP) analysis with a cut-off of ≤20 SNPs. Escherichia coli (14.3%), Klebsiella pneumoniae (10.9%) and Enterobacter cloacae (16.3%) were the main MDRE species isolated. The carbapenemase gene blaNDM was most commonly detected, with 15.5%, 15.1% and 13.3% of samples positive in SSIs, HSs and arthropods, respectively. SNP (≤20) and spatiotemporal analysis revealed linkages in bacteria between SSIs, HSs and arthropods supporting the One Health approach to underpin infection control policies across LMICs and control AMR.