Mechanisms of enterococcus faecalis pathogenesis in wound infection

Enterococci are among the most prevalent pathogens isolated from wound infections, and Enterococcus faecalis is typically in the top four most commonly isolated bacterial species in diabetic wounds. Despite its prevalence, very little is known about the pathogenic mechanisms of E. faecalis in wound...

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Main Author: Chong, Kelvin Kian Long
Other Authors: David Becker
Format: Theses and Dissertations
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/88850
http://hdl.handle.net/10220/47630
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-888502020-11-01T04:47:42Z Mechanisms of enterococcus faecalis pathogenesis in wound infection Chong, Kelvin Kian Long David Becker Kimberly Kline Interdisciplinary Graduate School (IGS) Singapore Centre for Environmental Life Sciences Engineering DRNTU::Science::Biological sciences Enterococci are among the most prevalent pathogens isolated from wound infections, and Enterococcus faecalis is typically in the top four most commonly isolated bacterial species in diabetic wounds. Despite its prevalence, very little is known about the pathogenic mechanisms of E. faecalis in wound infections. Our overall aim was to identify E. faecalis fitness factors in wounds and to understand the host-pathogen interplay that promotes infection. To achieve this aim, we established a mouse E. faecalis wound infection model to study its infection dynamics. High titer E. faecalis inocula into wounds resulted in acute bacterial replication with a concomitant pro-inflammatory neutrophilic response, followed by a reduction in bacterial burden that can persist within wounds with limited inflammation. To better understand the bacterial factors that contribute to chronic E. faecalis wounds, we collected 49 E. faecalis isolates from a variety of infected human wounds and performed comparative genomics. We found that E. faecalis wound isolates were predominantly clustered in ST16/179 and CC2/6. Isolates with the greatest in vitro biofilm-forming capacity correlated with the presence of ecbA, a putative cell wall surface anchor family protein that binds to collagen type V and fibrinogen, suggesting it may be a potential indicator of high biofilm formation in vivo. To elucidate additional E. faecalis wound fitness factors, we performed transposon sequencing and also tested E. faecalis mutants in a hypothesis-driven manner. We found that E. faecalis MprF, which confers resistance to cationic peptides, and a phosphotransferase system are required for E. faecalis persistence in wounds. In E. faecalis polymicrobial wound infections with S. aureus, we observed that E. faecalis can augment biofilm formation and titers, possibly through utilization of S. aureus-derived L-arginine. Together, these findings suggest that E. faecalis can both modulate the host immune response and tune its metabolism during monomicrobial and polymicrobial infections to mediate its persistence in wounds. Doctor of Philosophy 2019-02-11T05:11:15Z 2019-12-06T17:12:15Z 2019-02-11T05:11:15Z 2019-12-06T17:12:15Z 2018 Thesis Chong, K. K. L. (2018). Mechanisms of enterococcus faecalis pathogenesis in wound infection. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/88850 http://hdl.handle.net/10220/47630 10.32657/10220/47630 en 205 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Chong, Kelvin Kian Long
Mechanisms of enterococcus faecalis pathogenesis in wound infection
description Enterococci are among the most prevalent pathogens isolated from wound infections, and Enterococcus faecalis is typically in the top four most commonly isolated bacterial species in diabetic wounds. Despite its prevalence, very little is known about the pathogenic mechanisms of E. faecalis in wound infections. Our overall aim was to identify E. faecalis fitness factors in wounds and to understand the host-pathogen interplay that promotes infection. To achieve this aim, we established a mouse E. faecalis wound infection model to study its infection dynamics. High titer E. faecalis inocula into wounds resulted in acute bacterial replication with a concomitant pro-inflammatory neutrophilic response, followed by a reduction in bacterial burden that can persist within wounds with limited inflammation. To better understand the bacterial factors that contribute to chronic E. faecalis wounds, we collected 49 E. faecalis isolates from a variety of infected human wounds and performed comparative genomics. We found that E. faecalis wound isolates were predominantly clustered in ST16/179 and CC2/6. Isolates with the greatest in vitro biofilm-forming capacity correlated with the presence of ecbA, a putative cell wall surface anchor family protein that binds to collagen type V and fibrinogen, suggesting it may be a potential indicator of high biofilm formation in vivo. To elucidate additional E. faecalis wound fitness factors, we performed transposon sequencing and also tested E. faecalis mutants in a hypothesis-driven manner. We found that E. faecalis MprF, which confers resistance to cationic peptides, and a phosphotransferase system are required for E. faecalis persistence in wounds. In E. faecalis polymicrobial wound infections with S. aureus, we observed that E. faecalis can augment biofilm formation and titers, possibly through utilization of S. aureus-derived L-arginine. Together, these findings suggest that E. faecalis can both modulate the host immune response and tune its metabolism during monomicrobial and polymicrobial infections to mediate its persistence in wounds.
author2 David Becker
author_facet David Becker
Chong, Kelvin Kian Long
format Theses and Dissertations
author Chong, Kelvin Kian Long
author_sort Chong, Kelvin Kian Long
title Mechanisms of enterococcus faecalis pathogenesis in wound infection
title_short Mechanisms of enterococcus faecalis pathogenesis in wound infection
title_full Mechanisms of enterococcus faecalis pathogenesis in wound infection
title_fullStr Mechanisms of enterococcus faecalis pathogenesis in wound infection
title_full_unstemmed Mechanisms of enterococcus faecalis pathogenesis in wound infection
title_sort mechanisms of enterococcus faecalis pathogenesis in wound infection
publishDate 2019
url https://hdl.handle.net/10356/88850
http://hdl.handle.net/10220/47630
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