Chiang-Ni Chuan, Shi Yong-An, Lai Chih-Ho, Chiu Cheng-Hsun
Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Microbiol. 2018 Oct 30;9:2592. doi: 10.3389/fmicb.2018.02592. eCollection 2018.
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 mutants. Nonetheless, the encapsulated mutant is resistant to phagocytosis. The fate of intracellular mutant in phagocytic cells and whether the intracellular 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 mutant had better survival fitness than the cap wild-type strain in the PMA-activated U937 cells. In addition, the cap mutant caused more cell damages than the cap wild-type strain and encapsulated 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 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.
在CovR/CovS调节系统中具有自发突变的A组链球菌（GAS）更具侵袭性，且与严重临床表现相关。GAS可在吞噬细胞内复制；因此，吞噬细胞可作为选择侵袭性突变体的生态位。尽管如此，有荚膜的突变体对吞噬作用具有抗性。吞噬细胞内突变体的命运以及细胞内突变体是否导致侵袭性感染尚不清楚。在本研究中，利用无荚膜（cap）菌株来研究细胞内细菌如何与吞噬细胞相互作用。竞争感染模型的结果表明，在佛波酯激活的U937细胞中，cap突变体比cap野生型菌株具有更好的生存适应性。此外，cap突变体比cap野生型菌株和有荚膜突变体造成更多的细胞损伤。此外，用克林霉素处理感染细胞以抑制细胞内细菌生长，比用青霉素杀死细胞外细菌更有效地降低细菌毒性。这些结果不仅表明突变体可从吞噬细胞的细胞内生态位中被选择出来，还表明灭活或杀死细胞内GAS对于预防侵袭性感染可能至关重要。
