Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor best known for regulating cell proliferation and metabolism. PTEN forms a complex with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) at the plasma membrane, and this complex is known to be functionally impaired in CF. Here, we demonstrated that the combined effect of PTEN and CFTR dysfunction stimulates mitochondrial activity, resulting in excessive release of succinate and reactive oxygen species. This environment promoted the colonization of the airway by Pseudomonas aeruginosa, bacteria that preferentially metabolize succinate, and stimulated an anti-inflammatory host response dominated by immune-responsive gene 1 (IRG1) and itaconate. The recruitment of myeloid cells induced by these strains was inefficient in clearing the infection and increased numbers of phagocytes accumulated under CFTR-PTEN axis dysfunction. This central metabolic defect in mitochondrial function due to impaired PTEN activity contributes to P. aeruginosa infection in CF.

Urinary tract infection (UTI) is an extremely common infectious condition affecting people throughout the world. Increasing antibiotic resistance in pathogens causing UTI threatens our ability to continue to treat patients in the clinics.

21As the pandemic SARS-CoV-2 virus has spread globally its genome has diversified to 22 an extent that distinct clones can now be recognized, tracked, and traced. Identifying 23 clonal groups allows for assessment of geographic spread, transmission events, and 24 identification of new or emerging strains that may be more virulent or more 25 transmissible. Here we present a rapid, whole genome, allele-based method (GNUVID) 26 for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. This 27 sequence typing scheme can be updated with new genomic information extremely 28 rapidly, making our technique continually adaptable as databases grow. We show that 29 our method is consistent with phylogeny and recovers waves of expansion and 30 replacement of sequence types/clonal complexes in different geographical locations. 31 GNUVID is available as a command line application 32 (https://github.com/ahmedmagds/GNUVID). 33 34