Cytotoxicity and Survival Fitness of Invasive covS Mutant of Group A Streptococcus in Phagocytic Cells

Chuan Chiang-Ni,Cheng-Hsun Chiu,Yong-An Shi,Chih-Ho Lai

doi:10.3389/fmicb.2018.02592

Chuan Chiang-Ni, Cheng-Hsun Chiu + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2018.02592

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Abstract

Group A streptococci (GAS) with spontaneous mutations in the CovR/CovS regulatory system are more invasive and related to severe manifestations. GAS can replicate inside phagocytic cells; therefore, phagocytic cells could serve as the niche to select invasive covS mutants. Nonetheless, the encapsulated covS mutant is resistant to phagocytosis. The fate of intracellular covS mutant in phagocytic cells and whether the intracellular covS mutant contributes to invasive infections are unclear. In this study, capsule-deficient (cap-) strains were utilized to study how intracellular bacteria interacted with phagocytic cells. Results from the competitive infection model showed that the cap- covS mutant had better survival fitness than the cap- wild-type strain in the PMA-activated U937 cells. In addition, the cap- covS mutant caused more cell damages than the cap- wild-type strain and encapsulated covS mutant. Furthermore, treatments with infected cells with clindamycin to inhibit the intracellular bacteria growth was more effective to reduce bacterial toxicity than utilized penicillin to kill the extracellular bacteria. These results not only suggest that the covS mutant could be selected from the intracellular niche of phagocytic cells but also indicating that inactivating or killing intracellular GAS may be critical to prevent invasive infection.

Highlights

Streptococcus pyogenes is a Gram-positive human pathogen causing diseases including pharyngitis, scarlet fever, impetigo, cellulitis, necrotizing fasciitis, and toxic shock syndrome (Olsen and Musser, 2010)
To evaluate whether the decrease in the number of intracellular SCN157 was related to its cytotoxicity, the cell-association and intracellular survival amount and cytotoxicity of these Group A streptococci (GAS) strains under low multiplicity of infection (MOI) conditions (MOI = 0.5) were further evaluated
These results indicated that inactivation of streptolysin O (SLO) expression in covS mutant decreased its activity to compete with SCN156 in PMA-activated U937 cells

Summary

Introduction

Streptococcus pyogenes (group A Streptococcus, GAS) is a Gram-positive human pathogen causing diseases including pharyngitis, scarlet fever, impetigo, cellulitis, necrotizing fasciitis, and toxic shock syndrome (Olsen and Musser, 2010). Acquired prophages have been considered the critical genetic cause of increased GAS virulence and invasiveness (Beres et al, 2002; Aziz et al, 2004; Sumby et al, 2005). In another aspect, the growing evidence provided by generation sequencing analyses suggests that spontaneous mutations in the regulatory proteins of GAS are highly related to the increase in bacterial invasiveness and severe invasive infections (Friaes et al, 2015b).

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