<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>

ABSTRACT Biofilms formed by nontypeable Haemophilus influenzae (NTHI) bacteria play an important role in multiple respiratory tract diseases. Visual inspection of the morphology of biofilms formed during chronic infections shows distinct differences from biofilms formed in vitro. To better understan...

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Autores principales:	Jonathan R. Brown, Joseph Jurcisek, Vinal Lakhani, Ali Snedden, William C. Ray, Elaine M. Mokrzan, Lauren O. Bakaletz, Jayajit Das
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Chinchilla lanigera agent-based model biofilm host response in silico modeling in vivo Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/febc5233e12b4408b9af5d6b26c90fba
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spelling	oai:doaj.org-article:febc5233e12b4408b9af5d6b26c90fba2021-11-15T15:22:26Z<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>10.1128/mSphere.00254-192379-5042https://doaj.org/article/febc5233e12b4408b9af5d6b26c90fba2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00254-19https://doaj.org/toc/2379-5042ABSTRACT Biofilms formed by nontypeable Haemophilus influenzae (NTHI) bacteria play an important role in multiple respiratory tract diseases. Visual inspection of the morphology of biofilms formed during chronic infections shows distinct differences from biofilms formed in vitro. To better understand these differences, we analyzed images of NTHI biofilms formed in the middle ears of Chinchilla lanigera and developed an in silico agent-based model of the formation of NTHI biofilms in vivo. We found that, as in vitro, NTHI bacteria are organized in self-similar patterns; however, the sizes of NTHI clusters in vivo are more than 10-fold smaller than their in vitro counterparts. The agent-based model reproduced these patterns and suggested that smaller clusters occur due to elimination of planktonic NTHI cells by the host responses. Estimation of model parameters by fitting simulation results to imaging data showed that the effects of several processes in the model change during the course of the infection. IMPORTANCE Multiple respiratory illnesses are associated with formation of biofilms within the human airway by NTHI. However, a substantial amount of our understanding of the mechanisms that underlie NTHI biofilm formation is obtained from in vitro studies. Our in silico model that describes biofilm formation by NTHI within the middle ears of Chinchilla lanigera will help isolate processes potentially responsible for the differences between the morphologies of biofilms formed in vivo versus those formed in vitro. Thus, the in silico model can be used to glean mechanisms that underlie biofilm formation in vivo and connect those mechanisms to those obtained from in vitro experiments. The in silico model developed here can be extended to investigate potential roles of specific host responses (e.g., mucociliary clearance) on NTHI biofilm formation in vivo. The developed computational tools can also be used to analyze and describe biofilm formation by other bacterial species in vivo.Jonathan R. BrownJoseph JurcisekVinal LakhaniAli SneddenWilliam C. RayElaine M. MokrzanLauren O. BakaletzJayajit DasAmerican Society for MicrobiologyarticleChinchilla lanigeraagent-based modelbiofilmhost responsein silico modelingin vivoMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chinchilla lanigera agent-based model biofilm host response in silico modeling in vivo Microbiology QR1-502
spellingShingle	Chinchilla lanigera agent-based model biofilm host response in silico modeling in vivo Microbiology QR1-502 Jonathan R. Brown Joseph Jurcisek Vinal Lakhani Ali Snedden William C. Ray Elaine M. Mokrzan Lauren O. Bakaletz Jayajit Das <italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
description	ABSTRACT Biofilms formed by nontypeable Haemophilus influenzae (NTHI) bacteria play an important role in multiple respiratory tract diseases. Visual inspection of the morphology of biofilms formed during chronic infections shows distinct differences from biofilms formed in vitro. To better understand these differences, we analyzed images of NTHI biofilms formed in the middle ears of Chinchilla lanigera and developed an in silico agent-based model of the formation of NTHI biofilms in vivo. We found that, as in vitro, NTHI bacteria are organized in self-similar patterns; however, the sizes of NTHI clusters in vivo are more than 10-fold smaller than their in vitro counterparts. The agent-based model reproduced these patterns and suggested that smaller clusters occur due to elimination of planktonic NTHI cells by the host responses. Estimation of model parameters by fitting simulation results to imaging data showed that the effects of several processes in the model change during the course of the infection. IMPORTANCE Multiple respiratory illnesses are associated with formation of biofilms within the human airway by NTHI. However, a substantial amount of our understanding of the mechanisms that underlie NTHI biofilm formation is obtained from in vitro studies. Our in silico model that describes biofilm formation by NTHI within the middle ears of Chinchilla lanigera will help isolate processes potentially responsible for the differences between the morphologies of biofilms formed in vivo versus those formed in vitro. Thus, the in silico model can be used to glean mechanisms that underlie biofilm formation in vivo and connect those mechanisms to those obtained from in vitro experiments. The in silico model developed here can be extended to investigate potential roles of specific host responses (e.g., mucociliary clearance) on NTHI biofilm formation in vivo. The developed computational tools can also be used to analyze and describe biofilm formation by other bacterial species in vivo.
format	article
author	Jonathan R. Brown Joseph Jurcisek Vinal Lakhani Ali Snedden William C. Ray Elaine M. Mokrzan Lauren O. Bakaletz Jayajit Das
author_facet	Jonathan R. Brown Joseph Jurcisek Vinal Lakhani Ali Snedden William C. Ray Elaine M. Mokrzan Lauren O. Bakaletz Jayajit Das
author_sort	Jonathan R. Brown
title	<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
title_short	<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
title_full	<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
title_fullStr	<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
title_full_unstemmed	<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>
title_sort	<italic toggle="yes">in silico</italic> modeling of biofilm formation by nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content> <italic toggle="yes">in vivo</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/febc5233e12b4408b9af5d6b26c90fba
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<italic toggle="yes">In Silico</italic> Modeling of Biofilm Formation by Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> <italic toggle="yes">In Vivo</italic>

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