novel strategy for antimicrobial agent: role of exogenous carbon monoxide on suppressing Escherichia coli vitality and toxicity

ABSTRACT

Sepsis is a severe systemic inflammatory response mostly caused by gram-negative bacterial infections. The rates of mortality in sepsis patients remain high. To date little is known about whether exogenous carbon monoxide can directly or indirectly inhibit or even kill gram negative bacteria. In our study, we demonstrate a critical role of CO-releasing molecules in the suppressive effects on bacterial vitality and toxicity. We found the bacterial growth and colony forming were markedly suppressed in the presence of CORM-2 with significant cell damage, decreased or disappeared pili and flagella. In contrast, qRT-PCR showed the expression of fliA was downregulated, while dnaK and waaQ were upregulated in E. coli+CORM-2. Subsequent in vivo experiments showed the mouse survival in the CORM- 2 intervened-E.coli injection tended to improve with 60%-100% survival rates, and colony distribution in major organs were significantly decreased with attenuated histological damage. In parallel, cytokine levels and myeloperoxidase accumulation in livers and lungs decreased significantly compared with E. coli group. These data provide the first evidence and a potential strategy that exogenous carbon monoxide can significantly suppress bacterial vitality and toxicity. This may be associated with the regulatory functions of CORM-2 on the expression of essential genes [fliA, dnaK and waaQ] in E. coli