Spermidine enhances the survival of Streptococcus pyogenes M3 under oxidative stress

Streptococcus pyogenes, a host-restricted gram-positive pathogen during infection, initially adheres to the epithelia of the nasopharynx and respiratory tract of the human host, followed by disseminating to other organs and evading the host immune system. Upon phagocytosis, S. pyogenes encounters oxidative stress inside the macrophages. The role of polyamines in regulating various physiological functions including stress resistance in bacteria has been reported widely. Since S. pyogenes lacks the machinery for the biosynthesis of polyamines, the study aimed to understand the role of extracellular polyamines in the survival of S. pyogenes under oxidative stress environments. S. pyogenes being a catalase-negative organism, we report that its survival within the macrophages and H2O2 is enhanced by the presence of spermidine. The increased survival can be attributed to the upregulation of oxidative stress response genes such as sodM, npx, and mtsABC. In addition, spermidine influences the upregulation of virulence factors such as sagA, slo, and hasA. Also, spermidine leads to a decrease in hydrophobicity of the cell membrane and an increase in hyaluronic acid. This study suggests a role for extracellular spermidine in the survival of S. pyogenes under oxidative stress environments. Recognizing the factors that modulate S. pyogenes survival and virulence under stress will assist in understanding its interactions with the host.