The Wide World of Ribosomally Encoded Bacterial Peptides

Flaherty, Rebecca A.; Freed, Stefan D.; Lee, Shaun W.

doi:10.1371/journal.ppat.1004221

Cited by 29 publications

(22 citation statements)

References 29 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…T he production of low-molecular-weight antimicrobial peptides is a trait widely distributed among species of bacteria and archaea (1). Although a variety of functions has been assigned to these compounds (e.g., toxins, virulence factors, bacterial hormones), the bacteriocins have mainly been investigated due to their potential as alternatives to antibiotics and food preservatives (2)(3)(4).…”

mentioning

confidence: 99%

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

Azevedo

Bento

Ruiz

et al. 2015

Appl Environ Microbiol

View full text Add to dashboard Cite

b Some species of ruminal bacteria are known to produce antimicrobial peptides, but the screening procedures have mostly been based on in vitro assays using standardized methods. Recent sequencing efforts have made available the genome sequences of hundreds of ruminal microorganisms. In this work, we performed genome mining of the complete and partial genome sequences of 224 ruminal bacteria and 5 ruminal archaea to determine the distribution and diversity of bacteriocin gene clusters. A total of 46 bacteriocin gene clusters were identified in 33 strains of ruminal bacteria. Twenty gene clusters were related to lanthipeptide biosynthesis, while 11 gene clusters were associated with sactipeptide production, 7 gene clusters were associated with class II bacteriocin production, and 8 gene clusters were associated with class III bacteriocin production. The frequency of strains whose genomes encode putative antimicrobial peptide precursors was 14.4%. Clusters related to the production of sactipeptides were identified for the first time among ruminal bacteria. BLAST analysis indicated that the majority of the gene clusters (88%) encoding putative lanthipeptides contained all the essential genes required for lanthipeptide biosynthesis. Most strains of Streptococcus (66.6%) harbored complete lanthipeptide gene clusters, in addition to an open reading frame encoding a putative class II bacteriocin. Albusin B-like proteins were found in 100% of the Ruminococcus albus strains screened in this study. The in silico analysis provided evidence of novel biosynthetic gene clusters in bacterial species not previously related to bacteriocin production, suggesting that the rumen microbiota represents an underexplored source of antimicrobial peptides.T he production of low-molecular-weight antimicrobial peptides is a trait widely distributed among species of bacteria and archaea (1). Although a variety of functions has been assigned to these compounds (e.g., toxins, virulence factors, bacterial hormones), the bacteriocins have mainly been investigated due to their potential as alternatives to antibiotics and food preservatives (2-4). With the rise in antibiotic resistance among commensal and pathogenic strains of bacteria, there is an urgent need to identify and develop novel therapeutic strategies for clinical applications in human and animal health (5).Bacteriocins are often defined as ribosomally synthesized antimicrobial peptides produced by bacteria or archaea (6). Bacteriocins show great diversity in their chemical structures and mechanisms of action, and at least four main groups have been proposed to classify these antimicrobial agents (7). Class I contains posttranslationally modified antimicrobial peptides, such as lanthipeptides, sactipeptides, and lasso peptides, which differ in their molecular structures, their mechanisms of action, and the enzymatic apparatuses involved in modifying the precursor peptides (7,8). Class II bacteriocins consist of antimicrobial peptides without posttranslationally modified residues and ca...

show abstract

mentioning

confidence: 99%

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

Azevedo

Bento

Ruiz

et al. 2015

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…Online tools, such as BACTIBASE and BAGEL, mine target genomes for bacteriocin precursor genes [82,83,84]. Other tools such as antiSMASH expand their search parameters to identify not only bacteriocin-like precursor genes but other non-ribosomal classes of antibiotics and secondary metabolites [82,85] (Figure 5). Recently, these tools were combined to mine the genomes of anaerobic bacteria for RiPPs.…”

Section: Identification and Use Of Novel Ribosomally Encoded Peptimentioning

confidence: 99%

“…Many bacteriocins have been shown to have antimicrobial, antiviral and antitumor properties. Others have been shown to function as bacterial signaling molecules such as the competence signaling peptide (Csp) of Streptococcus intermedius or to serve as host virulence factors, such as SLS and Listeriolysin S from Group A Streptococcus and Listeria monocytogenes , respectively [80,82,93]. Although the functions of novel RiPPs may be inferred by gene gazing via sequence similarity to known bacteriocins and modifying enzymes, similarly modified bacteriocin candidates have been shown to have divergent functions when tested in vivo [80,94].…”

Section: Identification and Use Of Novel Ribosomally Encoded Peptimentioning

confidence: 99%

Using bacterial genomes and essential genes for the development of new antibiotics

Fields

Lee

McConnell

2017

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

The shrinking antibiotic development pipeline together with the global increase in antibiotic resistant infections requires that new molecules with antimicrobial activity are developed. Traditional empirical screening approaches of natural and non-natural compounds have identified the majority of antibiotics that are currently available, however this approach has produced relatively few new antibiotics over the last few decades. The vast amount of bacterial genome sequence information that has become available since the sequencing of the first bacterial genome more than 20 years ago holds potential for contributing to the discovery of novel antimicrobial compounds. Comparative genomic approaches can identify genes that are highly conserved within and between bacterial species, and thus may represent genes that participate in key bacterial processes. Whole genome mutagenesis studies can also identify genes necessary for bacterial growth and survival under different environmental conditions, making them attractive targets for the development of novel inhibitory compounds. In addition, transcriptomic and proteomic approaches can be used to characterize RNA and protein levels on a cellular scale, providing information on bacterial physiology that can be applied to antibiotic target identification. Finally, bacterial genomes can be mined to identify biosynthetic pathways that produce many intrinsic antimicrobial compounds and peptides. In this review, we provide an overview of past and current efforts aimed at using bacterial genomic data in the discovery and development of novel antibiotics.

show abstract

“…The minimal size for a functional epitope was determined with eight amino acids . In bacteria, an increasing number of small proteins with diverse physiological roles have been discovered and initial characterization shows that many have various important cellular functions including signal transduction, transport of ions and macromolecules, cell division, spore formation, morphogenesis and regulation of enzyme activity . The presence and function of small proteins in the third domain of life, archaea, are currently understudied.…”

Section: Introductionmentioning

confidence: 99%

Solution Structure and Dynamics of the Small Protein HVO_2922 from Haloferax volcanii

et al. 2019

View full text Add to dashboard Cite

Past sequencing campaigns overlooked small proteins as they seemed to be irrelevant due to their small size. However, their occurrence is widespread, and there is growing evidence that these small proteins are in fact functionally very important in organisms found in all kingdoms of life. Within a global proteome analysis for small proteins of the archaeal model organism Haloferax volcanii, the HVO_2922 protein has been identified. It is differentially expressed in response to changes in iron and salt concentrations, thus suggesting that its expression is stress‐regulated. The protein is conserved among Haloarchaea and contains an uncharacterized domain of unknown function (DUF1508, UPF0339 family protein). We elucidated the NMR solution structure, which shows that the isolated protein forms a symmetrical dimer. The dimerization is found to be concentration‐dependent and essential for protein stability and most likely for its functionality, as mutagenesis at the dimer interface leads to a decrease in stability and protein aggregation.

show abstract

The Wide World of Ribosomally Encoded Bacterial Peptides

Cited by 29 publications

References 29 publications

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

Using bacterial genomes and essential genes for the development of new antibiotics

Solution Structure and Dynamics of the Small Protein HVO_2922 from Haloferax volcanii

Contact Info

Product

Resources

About