Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

ABSTRACT Bacteriophages (phages) have been proposed as alternative therapeutics for the treatment of multidrug-resistant bacterial infections. However, there are major gaps in our understanding of the molecular events in bacterial cells that control how bacteria respond to phage predation. Using the...

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Autores principales:	Anushila Chatterjee, Julia L. E. Willett, Uyen Thy Nguyen, Brendan Monogue, Kelli L. Palmer, Gary M. Dunny, Breck A. Duerkop
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	bacteriophages Enterococcus antibiotic resistance transposons RNA-Seq Tn-Seq Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fff4a00a2a8042c3b5f5906594ff750b
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spelling	oai:doaj.org-article:fff4a00a2a8042c3b5f5906594ff750b2021-11-15T15:57:02ZParallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions10.1128/mBio.03120-192150-7511https://doaj.org/article/fff4a00a2a8042c3b5f5906594ff750b2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03120-19https://doaj.org/toc/2150-7511ABSTRACT Bacteriophages (phages) have been proposed as alternative therapeutics for the treatment of multidrug-resistant bacterial infections. However, there are major gaps in our understanding of the molecular events in bacterial cells that control how bacteria respond to phage predation. Using the model organism Enterococcus faecalis, we used two distinct genomic approaches, namely, transposon library screening and RNA sequencing, to investigate the interaction of E. faecalis with a virulent phage. We discovered that a transcription factor encoding a LytR family response regulator controls the expression of enterococcal polysaccharide antigen (epa) genes that are involved in phage infection and bacterial fitness. In addition, we discovered that DNA mismatch repair mutants rapidly evolve phage adsorption deficiencies, underpinning a molecular basis for epa mutation during phage infection. Transcriptomic profiling of phage-infected E. faecalis revealed broad transcriptional changes influencing viral replication and progeny burst size. We also demonstrate that phage infection alters the expression of bacterial genes associated with intra- and interbacterial interactions, including genes involved in quorum sensing and polymicrobial competition. Together, our results suggest that phage predation has the potential to influence complex microbial behavior and may dictate how bacteria respond to external environmental stimuli. These responses could have collateral effects (positive or negative) on microbial communities, such as the host microbiota, during phage therapy. IMPORTANCE We lack fundamental understanding of how phage infection influences bacterial gene expression and, consequently, how bacterial responses to phage infection affect the assembly of polymicrobial communities. Using parallel genomic approaches, we have discovered novel transcriptional regulators and metabolic genes that influence phage infection. The integration of whole-genome transcriptomic profiling during phage infection has revealed the differential regulation of genes important for group behaviors and polymicrobial interactions. Our work suggests that therapeutic phages could more broadly influence bacterial community composition outside their intended host targets.Anushila ChatterjeeJulia L. E. WillettUyen Thy NguyenBrendan MonogueKelli L. PalmerGary M. DunnyBreck A. DuerkopAmerican Society for MicrobiologyarticlebacteriophagesEnterococcusantibiotic resistancetransposonsRNA-SeqTn-SeqMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacteriophages Enterococcus antibiotic resistance transposons RNA-Seq Tn-Seq Microbiology QR1-502
spellingShingle	bacteriophages Enterococcus antibiotic resistance transposons RNA-Seq Tn-Seq Microbiology QR1-502 Anushila Chatterjee Julia L. E. Willett Uyen Thy Nguyen Brendan Monogue Kelli L. Palmer Gary M. Dunny Breck A. Duerkop Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
description	ABSTRACT Bacteriophages (phages) have been proposed as alternative therapeutics for the treatment of multidrug-resistant bacterial infections. However, there are major gaps in our understanding of the molecular events in bacterial cells that control how bacteria respond to phage predation. Using the model organism Enterococcus faecalis, we used two distinct genomic approaches, namely, transposon library screening and RNA sequencing, to investigate the interaction of E. faecalis with a virulent phage. We discovered that a transcription factor encoding a LytR family response regulator controls the expression of enterococcal polysaccharide antigen (epa) genes that are involved in phage infection and bacterial fitness. In addition, we discovered that DNA mismatch repair mutants rapidly evolve phage adsorption deficiencies, underpinning a molecular basis for epa mutation during phage infection. Transcriptomic profiling of phage-infected E. faecalis revealed broad transcriptional changes influencing viral replication and progeny burst size. We also demonstrate that phage infection alters the expression of bacterial genes associated with intra- and interbacterial interactions, including genes involved in quorum sensing and polymicrobial competition. Together, our results suggest that phage predation has the potential to influence complex microbial behavior and may dictate how bacteria respond to external environmental stimuli. These responses could have collateral effects (positive or negative) on microbial communities, such as the host microbiota, during phage therapy. IMPORTANCE We lack fundamental understanding of how phage infection influences bacterial gene expression and, consequently, how bacterial responses to phage infection affect the assembly of polymicrobial communities. Using parallel genomic approaches, we have discovered novel transcriptional regulators and metabolic genes that influence phage infection. The integration of whole-genome transcriptomic profiling during phage infection has revealed the differential regulation of genes important for group behaviors and polymicrobial interactions. Our work suggests that therapeutic phages could more broadly influence bacterial community composition outside their intended host targets.
format	article
author	Anushila Chatterjee Julia L. E. Willett Uyen Thy Nguyen Brendan Monogue Kelli L. Palmer Gary M. Dunny Breck A. Duerkop
author_facet	Anushila Chatterjee Julia L. E. Willett Uyen Thy Nguyen Brendan Monogue Kelli L. Palmer Gary M. Dunny Breck A. Duerkop
author_sort	Anushila Chatterjee
title	Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
title_short	Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
title_full	Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
title_fullStr	Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
title_full_unstemmed	Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
title_sort	parallel genomics uncover novel enterococcal-bacteriophage interactions
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/fff4a00a2a8042c3b5f5906594ff750b
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_version_	1718427069105307648

Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

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