Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

ABSTRACT Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target oth...

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Autores principales:	Natalie Maricic, Erica S. Anderson, AnneMarie E. Opipari, Emily A. Yu, Suzanne Dawid
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/174887d8e041413f95a5cc749274e5fa
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spelling	oai:doaj.org-article:174887d8e041413f95a5cc749274e5fa2021-11-15T15:49:40ZCharacterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>10.1128/mBio.01656-152150-7511https://doaj.org/article/174887d8e041413f95a5cc749274e5fa2016-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01656-15https://doaj.org/toc/2150-7511ABSTRACT Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus) in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials. IMPORTANCE Successful colonization of a polymicrobial host surface is a prerequisite for the subsequent development of disease for many bacterial pathogens. Bacterial factors that directly inhibit the growth of neighbors may provide an advantage during colonization if the inhibition of competitors outweighs the energy for production. In this work, we found that production of a potent antimicrobial called pneumolancidin conferred a competitive advantage to the pathogen Streptococcus pneumoniae. S. pneumoniae secreting pneumolancidin inhibits a wide array of Gram-positive organisms, including all but one tested pneumococcal strain. The pneumolancidin genetic locus is of particular interest because it encodes three similar modified peptides (lantibiotics), each of which has a distinct role in the function of the locus. Lantibiotics represent a relatively untapped resource for the development of clinically useful antibiotics which are desperately needed. The broad inhibitory activity of pneumolancidin makes it an ideal candidate for further characterization and development.Natalie MaricicErica S. AndersonAnneMarie E. OpipariEmily A. YuSuzanne DawidAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Natalie Maricic Erica S. Anderson AnneMarie E. Opipari Emily A. Yu Suzanne Dawid Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
description	ABSTRACT Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus) in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials. IMPORTANCE Successful colonization of a polymicrobial host surface is a prerequisite for the subsequent development of disease for many bacterial pathogens. Bacterial factors that directly inhibit the growth of neighbors may provide an advantage during colonization if the inhibition of competitors outweighs the energy for production. In this work, we found that production of a potent antimicrobial called pneumolancidin conferred a competitive advantage to the pathogen Streptococcus pneumoniae. S. pneumoniae secreting pneumolancidin inhibits a wide array of Gram-positive organisms, including all but one tested pneumococcal strain. The pneumolancidin genetic locus is of particular interest because it encodes three similar modified peptides (lantibiotics), each of which has a distinct role in the function of the locus. Lantibiotics represent a relatively untapped resource for the development of clinically useful antibiotics which are desperately needed. The broad inhibitory activity of pneumolancidin makes it an ideal candidate for further characterization and development.
format	article
author	Natalie Maricic Erica S. Anderson AnneMarie E. Opipari Emily A. Yu Suzanne Dawid
author_facet	Natalie Maricic Erica S. Anderson AnneMarie E. Opipari Emily A. Yu Suzanne Dawid
author_sort	Natalie Maricic
title	Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_short	Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full	Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_fullStr	Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full_unstemmed	Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_sort	characterization of a multipeptide lantibiotic locus in <named-content content-type="genus-species">streptococcus pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/174887d8e041413f95a5cc749274e5fa
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Characterization of a Multipeptide Lantibiotic Locus in <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

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