Award Abstract # 1808370
Chemical Biology Approaches to Interrogate Interspecies Communication in Streptococci

NSF Org: CHE
Division Of Chemistry
Recipient: BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED
Initial Amendment Date: June 27, 2018
Latest Amendment Date: June 24, 2019
Award Number: 1808370
Award Instrument: Standard Grant
Program Manager: Christine Chow
CHE
 Division Of Chemistry
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: July 1, 2018
End Date: June 30, 2023 (Estimated)
Total Intended Award Amount: $426,000.00
Total Awarded Amount to Date: $523,023.00
Funds Obligated to Date: FY 2018 = $471,329.00
FY 2019 = $51,694.00
History of Investigator:
  • Yftah Tal-Gan (Principal Investigator)
    ytalgan@unr.edu
Recipient Sponsored Research Office: Board of Regents, NSHE, obo University of Nevada, Reno
1664 N VIRGINIA ST # 285
RENO
NV  US  89557-0001
(775)784-4040
Sponsor Congressional District: 02
Primary Place of Performance: Board of Regents, NSHE, obo University of Nevada, Reno
1664 N. Virginia St.
Reno
NV  US  89557-0001
Primary Place of Performance
Congressional District:
02
Unique Entity Identifier (UEI): WLDGTNCFFJZ3
Parent UEI: WLDGTNCFFJZ3
NSF Program(s): OFFICE OF MULTIDISCIPLINARY AC,
Chemistry of Life Processes
Primary Program Source: 01001819DB NSF RESEARCH & RELATED ACTIVIT
01001920DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 068Z, 1515, 9150
Program Element Code(s): 125300, 688300
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049

ABSTRACT

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Yftah Tal-Gan from University of Nevada, Reno to investigate how bacteria communicate with each other. It has been well-established that bacteria utilize chemical signals to communicate, assess their population size, and alter their behaviors. Thus far, the focus was on studying the communication of bacteria within each species. However, the role of inter-species communications between different bacterial species in shaping the overall bacterial population was largely unexplored. Through the development of synthetic signal mimics that alter the behavior of one or more bacterial species, the effects of communications on the behavior of complex communities of bacteria (microbiomes) is determined. The discoveries of this project may provide means to manage bacterial communities in diverse ecosystems such as agriculture, biomanufacturing, and environmental management. This study allows high-school, undergraduate and graduate students, along with postdoctoral fellows to acquire specialized training in synthetic chemistry, analytical chemistry, microbiology, and molecular biology techniques. This project also integrates into two outreach programs to introduce high school and undergraduate students to research at the interface of chemistry and biology. Undergraduate students and faculty from Moravian College, a small liberal arts college in Bethlehem, Pennsylvania, participate hands on research. Many of these students come from socioeconomically disadvantaged and first generation college backgrounds and are trained for excellent jobs in STEM fields.

This project utilizes chemical tools to study the role of interspecies communication between streptococci. Bacterial species rely on a cell-cell signaling mechanism, termed quorum sensing (QS), and this allows related phenotypes to thrive in their natural habitat. Streptococci species utilize QS, an intra-species communication mechanism, to communicate with other streptococci species (i.e. inter-species communication) and employ different strategies to interfere with the communication of other streptococci as a means to dominate in a mixed bacterial population. This interdisciplinary project integrates chemical biology approaches with molecular biology techniques to delineate the molecular mechanism for QS interference between streptococci and define the role of QS in the interactions between streptococci in mixed bacterial milieu. Discoveries resulting from this project may improve the understanding of bacterial communication interference and competition beyond streptococci, and fundamentally advance the growing field of QS and sociomicrobiology. Moreover, the chemical probes to be developed in this study have the potential for broad applicability and can be used to study complex bacterial communities in their natural niches (microbiomes).

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

Note:  When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

(Showing: 1 - 10 of 17)
Bikash, Chowdhury Raihan and Hamry, Sally R. and Tal-Gan, Yftah "StructureActivity Relationships of the Competence Stimulating Peptide in Streptococcus mutans Reveal Motifs Critical for Membrane Protease SepM Recognition and ComD Receptor Activation" ACS Infectious Diseases , v.4 , 2018 10.1021/acsinfecdis.8b00115 Citation Details
Bikash, Chowdhury Raihan and Tal-Gan, Yftah "Identification of highly potent competence stimulating peptide-based quorum sensing activators in Streptococcus mutans through the utilization of N-methyl and reverse alanine scanning" Bioorganic & Medicinal Chemistry Letters , v.29 , 2019 10.1016/j.bmcl.2019.01.029 Citation Details
Brennan, Alec A. and Harrington, Anthony and Guo, Mingzhe and Renshaw, Clay P. and Tillett, Richard L. and Miura, Pedro and Tal-Gan, Yftah "Investigating the Streptococcus sinensis competence regulon through a combination of transcriptome analysis and phenotypic evaluation" Microbiology , v.168 , 2022 https://doi.org/10.1099/mic.0.001256 Citation Details
Brennan, Alec A. and Mehrani, Mona and Tal-Gan, Yftah "Modulating streptococcal phenotypes using signal peptide analogues" Open Biology , v.12 , 2022 https://doi.org/10.1098/rsob.220143 Citation Details
Harrington, Anthony and Proutière, Alexis and Mull, Ryan W. and du Merle, Laurence and Dramsi, Shaynoor and Tal-Gan, Yftah "Secretion, Maturation, and Activity of a Quorum Sensing Peptide (GSP) Inducing Bacteriocin Transcription in Streptococcus gallolyticus" mBio , v.12 , 2021 https://doi.org/10.1128/mBio.03189-20 Citation Details
Harrington, Anthony and Tal-Gan, Yftah "The importance of amide protons in peptide drug development" Future Medicinal Chemistry , v.11 , 2019 10.4155/fmc-2019-0238 Citation Details
Koirala, Bimal and Lin, Jingjun and Lau, Gee W. and Tal-Gan, Yftah "Development of a Dominant Negative Competence-Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia" ChemBioChem , v.19 , 2018 10.1002/cbic.201800505 Citation Details
Koirala, Bimal and Phillips, Naiya R and Tal-Gan, Yftah "Unveiling the Importance of Amide Protons in CSP:ComD Interactions in Streptococcus pneumoniae" ACS Medicinal Chemistry Letters , 2019 10.1021/acsmedchemlett.9b00038 Citation Details
Koirala, Bimal and TalGan, Yftah "Development of Streptococcus pneumoniae PanGroup QuorumSensing Modulators" ChemBioChem , v.21 , 2019 10.1002/cbic.201900365 Citation Details
McBrayer, Dominic N. and Cameron, Crissey D. and Gantman, Brooke K. and Tal-Gan, Yftah "Rational Design of Potent Activators and Inhibitors of the Enterococcus faecalis Fsr Quorum Sensing Circuit" ACS Chemical Biology , v.13 , 2018 10.1021/acschembio.8b00610 Citation Details
McBrayer, Dominic N and Gantman, Brooke K and Tal-Gan, Yftah "N-methylation of amino acids in Gelatinase Biosynthesis-Activating Pheromone (GBAP) Identifies Key Site for Stability Enhancement with Retention of the Enterococcus faecalis Fsr Quorum Sensing Circuit Response" ACS Infectious Diseases , 2019 10.1021/acsinfecdis.9b00097 Citation Details
(Showing: 1 - 10 of 17)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

This award from the Chemistry of Life Processes Program in the Chemistry Division funded Dr. Yftah Tal-Gan from University of Nevada, Reno. The research involved investigating communication mechanisms in Streptococci. The Tal-Gan group determined the effects of bacterial communications on the behavior of different bacterial species, through the development of synthetic signal mimetics that modulate bacterial communication pathways. The novel chemical tools discovered with the support of this project provided means to control bacterial behaviors, either in isolation, i.e., one bacterial species by itself, or as part of complex bacterial communities (microbiomes). These tools could have resounding impact on multiple disciplines, including agriculture, biomanufacturing, and environmental management, as they would allow promoting productvive bacterail processes while attenuating undesired behaviors. Overall, communication pathways in 8 different streptococci species were investigated. The results included: 1) developing novel chemical tools to modulate communication pathways; 2) defining the regulatory roles individual communication pathways have on bacterial behavior; and 3) delineating the molecular mechanisms for signal-receptor interactions.

This study allowed high-school, undergraduate and graduate students to acquire specialized training in synthetic peptide chemistry, analytical chemistry, microbiology, and molecular biology techniques. This project also integrated into an outreach program to introduce undergraduate students to research at the interface of chemistry and biology through an exchange program with two primarily undergraduate institutions in Pennsylvania: Moravian College and Lafayette College.


Last Modified: 07/05/2023
Modified by: Yftah Tal-Gan

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page