PMID- 34576085
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20211022
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 18
DP  - 2021 Sep 14
TI  - Bitter Taste Receptor T2R14 Modulates Gram-Positive Bacterial Internalization and 
      Survival in Gingival Epithelial Cells.
LID - 10.3390/ijms22189920 [doi]
LID - 9920
AB  - Bitter-taste receptors (T2Rs) have emerged as key players in host-pathogen 
      interactions and important modulators of oral innate immunity. Previously, we 
      reported that T2R14 is expressed in gingival epithelial cells (GECs) and 
      interacts with competence stimulating peptides (CSPs) secreted by the cariogenic 
      Streptococcus mutans. The underlying mechanisms of the innate immune responses 
      and physiological effects of T2R14 on Gram-positive bacteria are not well 
      characterized. In this study, we examined the role of T2R14 in internalization 
      and growth inhibitory effects on Gram-positive bacteria, namely Staphylococcus 
      aureus and S. mutans. We utilized CRISPR-Cas9 T2R14 knockdown (KD) GECs as the 
      study model to address these key physiological mechanisms. Our data reveal that 
      the internalization of S. aureus is significantly decreased, while the 
      internalization of S. mutans remains unaffected upon knockdown of T2R14 in GECs. 
      Surprisingly, GECs primed with S. mutans CSP-1 resulted in an inhibition of 
      growth for S. aureus, but not for S. mutans. The GECs infected with S. aureus 
      induced T2R14-dependent human beta-defensin-2 (hBD-2) secretion; however, S. 
      mutans-infected GECs did not induce hBD-2 secretion, but induced T2R14 dependent 
      IL-8 secretion. Interestingly, our results show that T2R14 KD affects the 
      cytoskeletal reorganization in GECs, thereby inhibiting S. aureus 
      internalization. Our study highlights the distinct mechanisms and a direct role 
      of T2R14 in influencing physiological responses to Gram-positive bacteria in the 
      oral cavity.
FAU - Medapati, Manoj Reddy
AU  - Medapati MR
AUID- ORCID: 0000-0002-6342-5546
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
FAU - Bhagirath, Anjali Yadav
AU  - Bhagirath AY
AUID- ORCID: 0000-0001-5175-0811
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
AD  - Children's Hospital Research Institute of Manitoba (CHRIM), University of 
      Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
FAU - Singh, Nisha
AU  - Singh N
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
FAU - Schroth, Robert J
AU  - Schroth RJ
AUID- ORCID: 0000-0002-6262-5378
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
AD  - Children's Hospital Research Institute of Manitoba (CHRIM), University of 
      Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
AD  - Department of Preventive Dental Sciences, Rady Faculty of Health Sciences, Dr. 
      Gerald Niznick College of Dentistry, University of Manitoba, 780 Bannatyne 
      Avenue, Winnipeg, MB R3E 0W2, Canada.
FAU - Bhullar, Rajinder P
AU  - Bhullar RP
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
FAU - Duan, Kangmin
AU  - Duan K
AUID- ORCID: 0000-0002-3016-786X
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
AD  - Children's Hospital Research Institute of Manitoba (CHRIM), University of 
      Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
FAU - Chelikani, Prashen
AU  - Chelikani P
AUID- ORCID: 0000-0003-1129-7957
AD  - Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Rady 
      Faculty of Health Sciences, Dr. Gerald Niznick College of Dentistry, University 
      of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada.
AD  - Children's Hospital Research Institute of Manitoba (CHRIM), University of 
      Manitoba, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
LA  - eng
GR  - PJT-159731/CAPMC/CIHR/Canada
GR  - UMGF and GETS funding/University of Manitoba/
PT  - Journal Article
DEP - 20210914
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Actins)
RN  - 0 (DEFB4A protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (beta-Defensins)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Actins/metabolism
MH  - Cell Line
MH  - *Endocytosis
MH  - Epithelial Cells/*metabolism/ultrastructure
MH  - Gingiva/*cytology
MH  - Gram-Positive Bacteria/*metabolism
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - *Microbial Viability
MH  - Models, Biological
MH  - Nitrates/metabolism
MH  - Nitrites/metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - Staphylococcus aureus/metabolism
MH  - Streptococcus mutans/metabolism
MH  - *Taste
MH  - beta-Defensins/metabolism
MH  - p21-Activated Kinases/metabolism
MH  - rac1 GTP-Binding Protein/metabolism
PMC - PMC8469602
OTO - NOTNLM
OT  - G-protein-coupled receptor (GPCR)
OT  - Gram-positive bacteria
OT  - bitter taste receptor (T2R)
OT  - gingival epithelial cell
OT  - host-microbe interaction
OT  - innate immunity
OT  - internalization
COIS- The authors declare that they have no conflict of interest with the contents of 
      this article.
EDAT- 2021/09/29 06:00
MHDA- 2023/02/25 06:00
PMCR- 2021/09/14
CRDT- 2021/09/28 01:18
PHST- 2021/08/26 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/09/11 00:00 [accepted]
PHST- 2021/09/28 01:18 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/09/14 00:00 [pmc-release]
AID - ijms22189920 [pii]
AID - ijms-22-09920 [pii]
AID - 10.3390/ijms22189920 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 14;22(18):9920. doi: 10.3390/ijms22189920.