Mol Biol Evol
December 2024
Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, caspase-5, caspase-11, and caspase-12 and CARD16, 17, and 18) each have unique evolutionary trajectories.
View Article and Find Full Text PDFCaspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, -5, -11, -12, and CARD16, 17, and 18) each have unique evolutionary trajectories.
View Article and Find Full Text PDFBefore environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted antimicrobials. We previously discovered that the bacterium , the causative agent of Legionnaires' disease, can compete with other microbes via a secreted molecule called HGA. Curiously, strains that produce HGA is not wholly immune to its toxicity, making it a mystery how these bacteria can withstand the "friendly fire" of potentially self-targeting antimicrobials during inter-bacterial battles.
View Article and Find Full Text PDFBackground: There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died.
Methods: Phages were given via nebulization through the mechanical ventilation circuit.
Objectives: To investigate the utility of recently approved delafloxacin and other fluoroquinolones against leading MDR bacterial pathogens under physiologically relevant conditions.
Methods: MIC and MBC assays were conducted for MDR strains of Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in the standard antibiotic susceptibility testing medium CAMHB, amended Roswell-Park Memorial Institute tissue culture medium (RPMI+) or 20% fresh human whole blood. In vivo correlation of in vitro findings was performed in a murine P.