A cytosol derived factor of Group B streptococcus prevent its invasion into human epithelial cells
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Group B streptococcus (GBS) or Streptococcus agalactiae, is an opportunistic pathogen causing a wide range of infections like pneumonia, sepsis, and meningitis in newborn, pregnant women and adults. While this bacterium has adapted well to asymptomatic colonization of adult humans, it still remains a potentially devastating pathogen to susceptible infants. Advances in molecular techniques and refinement of in vitro and in vivo model systems have elucidated key elements of the pathogenic process, from initial attachment to the maternal vaginal epithelium to penetration of the newborn blood–brain barrier. Still, the formidable array of GBS virulence factors makes this bacterium at the forefront of neonatal pathogens. The involvement of bacterial components in the host-pathogen interaction of GBS pathogenesis and its related diseases is not clearly understood. In this study we demonstrated the role of a 39 kDa factor from GBS which plays an important role in the process of its invasion. We found a homogeneous 39 kDa factor from the cytosol of GBS after following a combination of sequential purification steps involving molecular sieving and ion exchange chromatography using ACTA-FPLC system. Its N-terminal sequence showed a homology with xenobiotic response element type transcriptional regulator protein, a 40 kDa protein of Streptococcus. This factor leads to inhibition of GBS invasion in HeLa and A549 cells. This protein also showed sensitivity and specific cross reactivity with the antibodies raised against it in New Zealand white rabbits by western immunoblotting. This inhibitory factor was further confirmed tolerant for its cytotoxicity. These results add a novel aspect to bacterial pathogenesis where bacteria’s own intracellular protein component can act as a potential therapeutic candidate by decreasing the severity of disease thus promoting its invasion inhibition.
KeywordsInvasion Group B streptococcus (GBS) Pathogenesis Protein purification Invasion inhibition
We gratefully acknowledge Indian Council of Medical Research (ICMR) for providing the senior research fellowship to Manju Ohri (MO) to carry out this work. Prof. S. Majumdar is greatly acknowledged for invaluable guidance and PGIMER for Junior Research Fellowship to MO during this study. We would like to thank Dr. Harmeet Kaur who contributed in collection of all serotypes of GBS, Deepak Bhatt (IMTECH) and Central Instrumentation Lab (Panjab University) for assistance in microscopy.
Conceived and designed the experiments: MO, AC. Performed the experiments including invasion assays and protein purification: MO, SP. Microscopy experiments performed by MO. Analyzed the data AC, SG and MO. Wrote the paper MO, VSP, AC.
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Conflict of interest
The authors have declared that no conflict of interests exists.
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