SPD_0090 Negatively Contributes to Virulence of Streptococcus pneumoniae

Abstract

In most bacteria, iron plays an important role in the survival of bacteria and the process of infection to the host. Streptococcus pneumoniae (S. pneumoniae) evolved three iron transporters (i.e., PiaABC, PiuABC, and PitABC) responsible for the transportation of three kinds of iron (i.e., ferrichrome, hemin, and ferric ion). Our previous study showed that both mRNA and protein levels of SPD_0090 were significantly upregulated in the ΔpiuA/ΔpiaA/ΔpitA triple mutant, but its detailed biological function is unknown. In this study, we constructed spd_0090 knockout and complement strain and found that the deletion of spd_0090 hinders bacterial growth. SPD_0090 is located on the cell membrane and affects the hemin utilization ability of S. pneumoniae. The cell infection model showed that the knockout strain had stronger invasion and adhesion ability. Notably, knockout of the spd_0090 gene resulted in an enhanced infection ability of S. pneumoniae in mice by increasing the expression of virulence factors. Furthermore, iTRAQ quantitative proteomics studies showed that the knockout of spd_0090 inhibited carbon metabolism and thus suppressed bacterial growth. Our study showed that SPD_0090 negatively regulates the virulence of S. pneumoniae.

Endogenously produced H 2 O 2 is intimately involved in iron metabolism in Streptococcus pneumoniae

“…The elevated expression of pitD1 during growth in THYB NTA compared with THYB CHX is consistent with the observation that the ∆ piuBCDA strain imported less heme than the WT during growth in this medium, while the piu loss did not impact heme content during growth in THYB Chx . Interestingly, cells grown on hemoglobin iron in the presence of NTA downregulate the expression of spd_0090 (0.54-fold) , which is part of a recently described heme importer, and of piaA (0.43-fold), a ferrochrome-binding protein ( 18 ). The repression of spd_0090 and piaA genes suggests different regulation modalities for these transporters.…”

“…Similarly, the PiuBCDA transporter promotes streptococcal binding to heme and hemoglobin ( 16 ), but the substrate-binding component, PiuA, binds in vitro norepinephrine and enterobactin in higher affinity than heme ( 17 ). A recent study implicated an additional pneumococcal ABC transporter, spd_0088–0090 , in heme uptake ( 18 ). Due to the redundancy of iron uptake mechanisms, genetic knockouts in multiple transport systems are required before attenuated pneumococcal growth is observed ( 13 ).…”