Abstract
Streptococcus pneumoniae is a serious human respiratory pathogen. It generates hydrogen peroxide (H2O2) as part of its normal metabolism, yet it lacks enzymes that remove this oxidant. Here we show that lactoperoxidase and myeloperoxidase, two host enzymes present in the respiratory tract, convert bacterial H2O2 into HOSCN that S. pneumoniae can resist. We found that incubation of S. pneumoniae with myeloperoxidase in chloride-rich buffer killed the bacteria due to formation of toxic hypochlorous acid (HOCl). However, the addition of physiological concentrations of thiocyanate protected the bacteria. Similarly, S. pneumoniae remained viable in the presence of lactoperoxidase and thiocyanate even though the majority of bacterial H2O2 was converted to hypothiocyanous acid (HOSCN). S. pneumoniae and Pseudomonas aeruginosa, another respiratory pathogen, were similarly sensitive to H2O2 and HOCl. In contrast, S. pneumoniae tolerated much higher doses of HOSCN than P. aeruginosa. When associated with neutrophil extracellular traps (NETs), S. pneumoniae continued to generate H2O2, which was converted to HOCl by myeloperoxidase (MPO) present on NETs. However, there was no loss in bacterial viability because HOCl was scavenged by the NET proteins. We conclude that at sites of infection, bacteria will be protected from HOCl by thiocyanate and extracellular proteins including those associated with NETs. Resistance to HOSCN may give S. pneumoniae a survival advantage over other pathogenic bacteria. Understanding the mechanisms by which S. pneumoniae protects itself from HOSCN may reveal novel strategies for limiting the colonization and pathogenicity of this deadly pathogen.