Exploring structural diversity in quorum sensing signalling systems and strategies to control prokaryotic community-wide behaviour

Christopher Jonkergouw

Exploring structural diversity in quorum sensing signalling systems and strategies to control prokaryotic community-wide behaviour

Julkaisun otsikon käännös: Tutkimus quorum sensing -viestintäjärjestelmien rakenteellisesta monimuotoisuudesta ja menetelmistä prokaryoottiyhteisöjen käyttäytymisen ohjaamiseksi

Christopher Jonkergouw

Tutkimustuotos: Doctoral Thesis › Collection of Articles

Abstrakti

Bakteerit, vaikka ovatkin yksisoluisia organismeja, kykenevät muodostamaan monimutkaisia yhteisöjä, joissa yksittäiset solut tekevät yhteistyötä kollektiivisen hyödyn nimissä. Yhteistyökyky ja järjestäytyminen ovat mahdollisia solujen välisen ryhmäviestinnän eli niin kutsutun quorum sensing (QS) -viestinnän ansiosta. Näissä yhteisöissä bakteerit osallistuvat monenlaisiin yhteistyötoimintoihin, kuten biofilmin muodostuksen, virulenssin, antimikrobisten aineiden tuotannon, ravinteiden jakamisen ja puolustautumisen säätelyyn. Bakteerien uskomaton sopeutumiskyky ja kestävyys näissä yhteisöissä korostavat solujenvälisen kommunikaation ja yhteistyön merkitystä, myös yksinkertaisimmissa organismeissa. Tässä työssä tutkimme erilaisten QS-viestintäjärjestelmien toimintaa ja, selvitämme kuinka QS-viestinnän hallintaa voidaan käyttää hyödyksi useissa bioteknologisissa sovelluksissa. Ensin tutkimme QS-järjestelmien laajaa monimuotoisuutta ja käytimme uusia laskennallisia työkaluja ymmärtääksemme, miten QS-viestintäjärjestelmät vuorovaikuttavat keskenään. Ennusteiden pohjalta tutkimme 10 QS-järjestelmää, joista tunnistimme kuusi täysin komplementaarista QS-järjestelmää. Tutkimme strategioita QS-viestinnän hallitsemiseksi ja häiritsemiseksi bakteeripatogeeneissä, jotka käyttävät QS:ää säädelläkseen taudinaiheuttamiskykyään infektioissa. Tutkimme myös QS-häirinnän potentiaalia vähentää taudinaiheuttajien vastustuskykyä antibioteille, sekä in vitro että in vivo. Lopuksi tutkimme uusia mikrofluidisia viljelytekniikoita rakentaaksemme mikrobiyhteisöjä alhaalta ylöspäin. Tässä QS-viestintää käytettiin koordinoimaan eri populaatioiden käyttäytymistä yhteisössä. Menetelmää jalostamalla kehitimme uuden 2-fotonipolymeerisaatiotekniikan, joka mahdollistaa neljästä eri populaatiosta koostuvien vakaiden mikrobiyhteisöjen rakentamisen. Yhteenvetona, QS-viestintäjärjestelmät ovat ratkaisevan tärkeitä bakteerien koordinoidussakäyttäytymisessä, mahdollistaen niiden kollektiivisen toiminnan ryhmänä. Osoitamme, että QS:n hyödyntämisellä voimme hallita bakteeriyhteisöjä sekä toiminnallistaa niiden kollektiivista käyttäytymistä.

Julkaisun otsikon käännös	Tutkimus quorum sensing -viestintäjärjestelmien rakenteellisesta monimuotoisuudesta ja menetelmistä prokaryoottiyhteisöjen käyttäytymisen ohjaamiseksi
Alkuperäiskieli	Englanti
Pätevyys	Tohtorintutkinto
Myöntävä instituutio	Aalto-yliopisto
Valvoja/neuvonantaja	Linder, Markus, Vastuuprofessori
Kustantaja	Aalto University
Painoksen ISBN	978-952-64-1612-0
Sähköinen ISBN	978-952-64-1613-7
Tila	Julkaistu - 2023
OKM-julkaisutyyppi	G5 Artikkeliväitöskirja

Tutkimusalat

bakteerien viestintä
quorum sensing
mikrobilääkeresistenssi
antivirulenssi
mikrobiyhteisöt

Pääsy asiakirjaan

http://urn.fi/URN:ISBN:978-952-64-1613-7

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Rissanen, A. (Manager)
Aalto-yliopisto
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Repo, P. (Manager) & Rissanen, A. (Other)
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Laitteistot/tilat: Facility
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Seitsonen, J. (Manager) & Rissanen, A. (Other)
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@phdthesis{5976325a78b44fb88ad4b57421547489,

title = "Exploring structural diversity in quorum sensing signalling systems and strategies to control prokaryotic community-wide behaviour",

abstract = "Bacteria, despite being single-celled organisms, have the ability to establish intricate communities where individual cells collaborate for the collective benefit. This cooperative behaviours and spatial organization are facilitated by cell-to-cell communication mediated by quorum sensing (QS). Within these communities, bacteria engage in diverse cooperative activities, including the regulation of biofilm formation, virulence, production of antimicrobials, nutrient sharing, and defence against external challenges. The remarkable adaptability and resilience exhibited by bacteria in these communities underscore the significance of intercellular communication and collaboration, even in the most basic organisms. In this work, we studied the function of various QS signalling systems and explore how having control over QS communication, can be utilized towards several biotechnological applications. First, we theoretically explored the wide diversity in QS signalling systems and use novel computational tools to understand how QS signalling systems interact with one another. These predictions were used to experimentally investigate a set of 10 QS signalling systems, among which we identified six fully complementary QS signalling systems. Then, we investigated strategies to control and disrupt communication in bacterial pathogens that utilize QS to regulate their virulence during infections. We further studied the potential of QS disruption as a potent strategy to combat antibiotic resistance bacteria, both in vitro and in vivo. Finally, we explored novel microfluidic culturing techniques to build microbial communities in a bottomup approach. In this, QS signalling was utilized to coordinate the behaviour of distinct populations acting within the community. From these studies, we improved upon the method and developed a novel 2-photon polymerization technique to enable stable microbial communities of bacteria consisting of four individual populations. In summary, QS signalling systems play a crucial role in facilitating coordinated behaviours among bacteria, enabling them to act collectively as a group. Here, we show that by harnessing the power of QS, we can exert control over bacterial communities and shape and functionalize their collective behaviour.",

keywords = "bacterial signalling, quorum sensing, antimicrobial resistance, anti-virulence, microbial communities, bakteerien viestint{\"a}, quorum sensing, mikrobil{\"a}{\"a}keresistenssi, antivirulenssi, mikrobiyhteis{\"o}t, bacterial signalling, quorum sensing, antimicrobial resistance, anti-virulence, microbial communities",

author = "Christopher Jonkergouw",

year = "2023",

language = "English",

isbn = "978-952-64-1612-0",

series = "Aalto University publication series DOCTORAL THESES",

publisher = "Aalto University",

number = "232",

address = "Finland",

school = "Aalto University",

}

TY - BOOK

T1 - Exploring structural diversity in quorum sensing signalling systems and strategies to control prokaryotic community-wide behaviour

AU - Jonkergouw, Christopher

PY - 2023

Y1 - 2023

N2 - Bacteria, despite being single-celled organisms, have the ability to establish intricate communities where individual cells collaborate for the collective benefit. This cooperative behaviours and spatial organization are facilitated by cell-to-cell communication mediated by quorum sensing (QS). Within these communities, bacteria engage in diverse cooperative activities, including the regulation of biofilm formation, virulence, production of antimicrobials, nutrient sharing, and defence against external challenges. The remarkable adaptability and resilience exhibited by bacteria in these communities underscore the significance of intercellular communication and collaboration, even in the most basic organisms. In this work, we studied the function of various QS signalling systems and explore how having control over QS communication, can be utilized towards several biotechnological applications. First, we theoretically explored the wide diversity in QS signalling systems and use novel computational tools to understand how QS signalling systems interact with one another. These predictions were used to experimentally investigate a set of 10 QS signalling systems, among which we identified six fully complementary QS signalling systems. Then, we investigated strategies to control and disrupt communication in bacterial pathogens that utilize QS to regulate their virulence during infections. We further studied the potential of QS disruption as a potent strategy to combat antibiotic resistance bacteria, both in vitro and in vivo. Finally, we explored novel microfluidic culturing techniques to build microbial communities in a bottomup approach. In this, QS signalling was utilized to coordinate the behaviour of distinct populations acting within the community. From these studies, we improved upon the method and developed a novel 2-photon polymerization technique to enable stable microbial communities of bacteria consisting of four individual populations. In summary, QS signalling systems play a crucial role in facilitating coordinated behaviours among bacteria, enabling them to act collectively as a group. Here, we show that by harnessing the power of QS, we can exert control over bacterial communities and shape and functionalize their collective behaviour.

AB - Bacteria, despite being single-celled organisms, have the ability to establish intricate communities where individual cells collaborate for the collective benefit. This cooperative behaviours and spatial organization are facilitated by cell-to-cell communication mediated by quorum sensing (QS). Within these communities, bacteria engage in diverse cooperative activities, including the regulation of biofilm formation, virulence, production of antimicrobials, nutrient sharing, and defence against external challenges. The remarkable adaptability and resilience exhibited by bacteria in these communities underscore the significance of intercellular communication and collaboration, even in the most basic organisms. In this work, we studied the function of various QS signalling systems and explore how having control over QS communication, can be utilized towards several biotechnological applications. First, we theoretically explored the wide diversity in QS signalling systems and use novel computational tools to understand how QS signalling systems interact with one another. These predictions were used to experimentally investigate a set of 10 QS signalling systems, among which we identified six fully complementary QS signalling systems. Then, we investigated strategies to control and disrupt communication in bacterial pathogens that utilize QS to regulate their virulence during infections. We further studied the potential of QS disruption as a potent strategy to combat antibiotic resistance bacteria, both in vitro and in vivo. Finally, we explored novel microfluidic culturing techniques to build microbial communities in a bottomup approach. In this, QS signalling was utilized to coordinate the behaviour of distinct populations acting within the community. From these studies, we improved upon the method and developed a novel 2-photon polymerization technique to enable stable microbial communities of bacteria consisting of four individual populations. In summary, QS signalling systems play a crucial role in facilitating coordinated behaviours among bacteria, enabling them to act collectively as a group. Here, we show that by harnessing the power of QS, we can exert control over bacterial communities and shape and functionalize their collective behaviour.

KW - bacterial signalling

KW - quorum sensing

KW - antimicrobial resistance

KW - anti-virulence

KW - microbial communities

KW - bakteerien viestintä

KW - quorum sensing

KW - mikrobilääkeresistenssi

KW - antivirulenssi

KW - mikrobiyhteisöt

KW - bacterial signalling

KW - quorum sensing

KW - antimicrobial resistance

KW - anti-virulence

KW - microbial communities

M3 - Doctoral Thesis

SN - 978-952-64-1612-0

T3 - Aalto University publication series DOCTORAL THESES

PB - Aalto University

ER -

Exploring structural diversity in quorum sensing signalling systems and strategies to control prokaryotic community-wide behaviour

Abstrakti

Tutkimusalat

Pääsy asiakirjaan

Sormenjälki

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