Activation of heme oxygenase expression by cobalt protoporphyrin treatment prevents pneumonic plague caused by inhalation of Yersinia pestis.

Activation of heme oxygenase expression by cobalt protoporphyrin treatment prevents pneumonic plague caused by inhalation of Yersinia pestis. Antimicrob Agents Chemother. 2020 Feb 03;: Authors: Willix JL, Stockton JL, Olson RM, Anderson PE, Anderson DM Abstract Pneumonic plague, caused by the gram-negative bacteria Yersinia pestis, is an invasive, rapidly progressing disease with poor survival rates. Following inhalation of Y. pestis, bacterial invasion of the lungs and a tissue-damaging inflammatory response allows vascular spread of the infection. Consequently, primary pneumonic plague is a multi-organ disease involving sepsis, necrosis of immune tissues and the liver, as well as bronchopneumonia and rampant bacterial growth. Given the likely role of the hyper-inflammatory response in accelerating the destruction of tissue, in this work we evaluated the therapeutic potential of the inducible cytoprotective enzyme heme oxygenase 1 (HO-1) against primary pneumonic plague. On its own, the HO-1 inducer cobalt protoporphyrin IX (CoPP) provided mice protection from lethal challenge with Y. pestis CO92 with improved pulmonary bacterial clearance and a dampened inflammatory response compared to vehicle-treated mice. Furthermore, CoPP treatment combined with doxycycline strongly enhanced protection in a rat aerosol challenge model. Compared to doxycycline alone, CoPP treatment increased survival, with a 3-log decrease in median bacterial ti...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research