Table_2_Group A Streptococcus NAD-Glycohydrolase Inhibits Caveolin 1-Mediated Internalization Into Human Epithelial Cells.pdf
Group A Streptococcus (GAS) invades epithelial cells causing persistent infection. GAS has a variety of effector proteins that modulate host systems to affect their survival in host environments. The main effector proteins of GAS are NAD-glycohydrolase (Nga) and streptolysin O (SLO). Although Nga has NADase activity and shows SLO-dependent cytotoxicity, some clinical isolates harbor NADase-inactive subtypes of Nga, and the function of NADase-inactive Nga is still unclear. In this study, we found that deletion of nga enhanced the internalization of GAS into HeLa and Ca9-22 cells. Amino acid substitution of Nga R289K/G330D (NADase-inactive) does not enhance GAS invasion, suggesting that Nga may inhibit the internalization of GAS into host cells in an NADase-independent manner. Moreover, double deletion of slo and nga showed similar invasion percentages compared with wild-type GAS, indicating the important role of SLO in the inhibition of GAS invasion by Nga. Furthermore, enhanced internalization of the nga deletion mutant was not observed in Cav1-knockout HeLa cells. Altogether, these findings demonstrate an unrecognized NADase-independent function of Nga as a negative regulator of CAV1-mediated internalization into epithelial cells.
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References
- https://doi.org//10.1016/0014-5793(87)81566-1
- https://doi.org//10.1046/j.1365-2958.2003.03797.x
- https://doi.org//10.1016/j.chom.2013.11.003
- https://doi.org//10.1128/mBio.01690-14
- https://doi.org//10.1046/j.1365-2958.2002.02876.x
- https://doi.org//10.1111/cmi.12442
- https://doi.org//10.1128/mBio.02215-15
- https://doi.org//10.1074/jbc.M113.481556
- https://doi.org//10.1128/JCM.00202-09
- https://doi.org//10.7554/eLife.00926.024
- https://doi.org//10.1128/CMR.13.3.470-511.2000
- https://doi.org//10.1078/0171-9335-00104
- https://doi.org//10.1074/jbc.M301915200
- https://doi.org//10.1074/jbc.M109.070300
- https://doi.org//10.1128/mBio.00756-17
- https://doi.org//10.1242/jcs.064006
- https://doi.org//10.3389/fmicb.2018.01733
- https://doi.org//10.1074/jbc.M807920200
- https://doi.org//10.1128/JB.185.4.1208-1217.2003
- https://doi.org//10.1126/science.1247136
- https://doi.org//10.1074/jbc.M506879200
- https://doi.org//10.1016/j.bbaexp.2004.10.011
- https://doi.org//10.1074/jbc.M313613200
- https://doi.org//10.1111/j.1462-5822.2006.00740.x
- https://doi.org//10.1093/infdis/jiu152
- https://doi.org//10.1111/cmi.12772
- https://doi.org//10.1016/j.devcel.2010.06.010
- https://doi.org//10.1128/mBio.00332-10
- https://doi.org//10.1016/S0092-8674(01)00198-2
- https://doi.org//10.1038/embor.2010.37
- https://doi.org//10.1074/jbc.M511674200
- https://doi.org//10.1046/j.1462-5822.2000.00040.x
- https://doi.org//10.1038/296651a0
- https://doi.org//10.1111/mmi.13085
- https://doi.org//10.1073/pnas.92.22.10339
- https://doi.org//10.1126/science.1103966
- https://doi.org//10.1093/infdis/171.4.871
- https://doi.org//10.1016/S0140-6736(97)12452-7
- https://doi.org//10.1371/journal.pone.0147061
- https://doi.org//10.1111/j.1432-1033.2004.04117.x
- https://doi.org//10.1371/journal.ppat.1003394
- https://doi.org//10.1084/jem.176.2.415
- https://doi.org//10.1038/35074539
- https://doi.org//10.1128/JB.00234-10
- https://doi.org//10.1046/j.1462-5822.2003.00279.x
- https://doi.org//10.1371/journal.pone.0170612
- https://doi.org//10.1038/nmicrobiol.2016.25
- https://doi.org//10.1007/s00418-009-0651-8
- https://doi.org//10.1371/journal.ppat.1005468
- https://doi.org//10.1073/pnas.1412703111
- https://doi.org//10.1242/jcs.014977
- https://doi.org//10.1038/ncomms7867
- https://doi.org//10.1046/j.1462-5822.1999.00011.x
- https://doi.org//10.1016/j.str.2010.12.013
- https://doi.org//10.1086/315850
- https://doi.org//10.1006/plas.2001.1532
- https://doi.org//10.1074/jbc.M209133200
- https://doi.org//10.1128/IAI.73.10.6199-6209.2005
- https://doi.org//10.1128/mBio.01382-17
- https://doi.org//10.1128/CMR.00101-13
