Biofilm Formation and Invasive Ability Contribute to CC17 Serotype III Group B Streptococcus Virulence
Group B Streptococcus (GBS) is a significant pathogen that colonizes the vagina and rectum of 7–30% of pregnant women, leading to materno-neonatal invasive infections. Despite its clinical importance, the pathogenesis of GBS strains remains poorly understood. Recent studies have highlighted the hypervirulent clonal complex 17 (CC17) of GBS, particularly serotype III, which is associated with severe invasive diseases such as bacteremia and meningitis in neonates. This article delves into the mechanisms by which CC17 serotype III GBS exerts its virulence, focusing on biofilm formation, invasive ability, and interactions with host immune cells.
The study involved 14 clinical GBS isolates, comprising seven CC17 serotype III isolates from the blood or cerebral spinal fluid of neonates (invasive isolates) and seven CC23 serotype Ia isolates from vaginal and rectal swabs of asymptomatic pregnant women (colonizing isolates). The Ethics Committee of Beijing Tsinghua Changgung Hospital approved the study, and informed consent was exempted as the privacy of subjects was not affected.
GBS persistence in host niches is crucial for invasion, with biofilm formation in vaginal environments playing a pivotal role. To assess biofilm formation, a microtiter plate assay was conducted. Overnight cultures of GBS were diluted and inoculated into 96-well plates, incubated for 48 hours, and stained with crystal violet. Biofilm production was quantified by measuring absorbance at 550 nm. Isolates with an absorbance greater than 0.5 were classified as biofilm producers. The results revealed that 85.71% of CC17 isolates were biofilm producers, compared to none of the CC23 isolates, indicating a strong correlation between the hypervirulent CC17 clone and biofilm-forming ability.
The invasion of GBS into epithelial cells is a critical step in causing infections. To evaluate this, the cytotoxicity of GBS to human VK2 vaginal epithelial cells was measured using a Cytotoxicity LDH Assay. VK2 cells were infected with GBS isolates, and cytotoxicity was determined after one hour of incubation. CC17 serotype III isolates induced significantly higher cytotoxicity (15.79 ± 3.28%) compared to CC23 serotype Ia isolates (6.96 ± 1.25%), demonstrating the enhanced invasive ability of the CC17 sublineage.
Host immune responses play a crucial role in combating GBS infections. Dendritic cells (DCs) internalize GBS and secrete pro-inflammatory cytokines in response. The study analyzed phagocytosis and cytokine secretion by DCs to understand the pathogenesis of hypervirulent GBS CC17. DC2.4 cells were infected with GBS isolates, and intracellular bacteria were enumerated after two hours. CC23 serotype Ia isolates were phagocytosed more effectively (8505 ± 3327 CFU/mL) than CC17 serotype III isolates (1157 ± 409 CFU/mL). Additionally, CC17 isolates stimulated DC2.4 cells to release significantly more interleukin 12 p70 (IL-12p70) (127.80 ± 40.88 pg/mL) compared to CC23 isolates (8.10 ± 4.15 pg/mL). Conversely, CC23 isolates induced higher levels of transforming growth factor-beta 1 (TGF-β1) (518.10 ± 27.83 pg/mL) than CC17 isolates (426.30 ± 21.18 pg/mL). These findings suggest that CC17 serotype III isolates are more resistant to internalization by DCs and stimulate a robust pro-inflammatory response, whereas CC23 isolates tend to maintain colonization status by inducing TGF-β1 production.
In summary, the study highlights the critical role of biofilm formation and invasive ability in the virulence of CC17 serotype III GBS. The enhanced biofilm-forming capability of CC17 isolates facilitates their persistence in host niches, while their increased cytotoxicity and resistance to phagocytosis contribute to their invasive potential. Furthermore, the differential cytokine responses elicited by CC17 and CC23 isolates underscore the distinct pathogenic mechanisms of these GBS sublineages. Future research is needed to elucidate the downstream mechanisms of hypervirulent CC17 strains’ pathogenicity, which could inform the development of targeted therapeutic strategies.
doi.org/10.1097/CM9.0000000000001861
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