Polyamines (
putrescine and
spermidine) are small-cationic
amines ubiquitous in nature and present in most living cells. In recent years they have been linked to virulence of several human pathogens including Shigella spp and Salmonella enterica serovar Typhimurium (S. Typhimurium). Central to S. Typhimurium virulence is the ability to survive and replicate inside macrophages and resisting the antimicrobial attacks in the form of oxidative and nitrosative stress elicited from these cells. In the present study, we have investigated the role of
polyamines in intracellular survival and systemic
infections of mice. Using a S. Typhimurium mutant defective for
putrescine and
spermidine biosynthesis, we show that
polyamines are essential for coping with
reactive nitrogen species, possibly linking
polyamines to increased intracellular stress resistance. However, using a mouse model defective for
nitric oxide production, we find that
polyamines are required for systemic
infections independently of host-produced
reactive nitrogen species. To distinguish between the physiological roles of
putrescine and
spermidine, we constructed a strain deficient for
spermidine biosynthesis and uptake, but with retained ability to produce and import
putrescine. Interestingly, in this mutant we observe a strong attenuation of virulence during
infection of mice proficient and deficient for
nitric oxide production suggesting that
spermidine, specifically, is essential for virulence of S. Typhimurium.