Genome Sequencing Reveals a Large and Diverse Repertoire of Antimicrobial Peptides

Abstract

Competition among bacterial members of the same ecological niche is mediated by bacteriocins: antimicrobial peptides produced by bacterial species to kill other bacteria. Bacteriocins are also promising candidates for novel antimicrobials. Streptococcus pneumoniae (the “pneumococcus”) is a leading cause of morbidity and mortality worldwide and a frequent colonizer of the human nasopharynx. Here, 14 newly discovered bacteriocin gene clusters were identified among >6,200 pneumococcal genomes. The molecular epidemiology of the bacteriocin clusters was investigated using a large global and historical pneumococcal dataset dating from 1916. These analyses revealed extraordinary bacteriocin diversity among pneumococci and the majority of bacteriocin clusters were also found in other streptococcal species. Genomic hotspots for the integration of different bacteriocin gene clusters were discovered. Experimentally, bacteriocin genes were transcriptionally active when the pneumococcus was under stress and when two strains were co-cultured in broth. These findings reveal much more diversity among bacterial defense mechanisms than previously appreciated, which fundamentally broaden our understanding of bacteriocins relative to intraspecies and interspecies nasopharyngeal competition and bacterial population structure.

The pneumococcal social network

“…Other examples include the bacteriocin-inducing peptide (BIP) [ 19 ], the competence-induced bacteriocins (CibA and CibB) [ 20 ], peptides of the bacteriocin immunity region (BIR) [ 21 ], the virulence peptide 1 (VP1) [ 22 ], the biofilm-regulating peptide induced by competence (BriC) [ 23 , 24 ], peptides of the rtg locus [ 25 ], and LanA [ 22 , 26 ] ( Table 1 , S1 Table ). Furthermore, comparative genomic approaches have revealed additional double-glycine peptides that remain to be characterized [ 22 , 27 ].…”

“… *Putative, lacks direct experimental evidence. # Categorized based on presence in strains tested in published data sets above in addition to Javan et al [ 27 ]: Rare: Less than 10%, Accessory: 10%–90%, Core or Almost Core: More than 90%. ## Contains an alternative start codon 33 bp upstream in D39.…”

“… # Categorized based on presence in strains tested in published data sets above in addition to Javan et al [ 27 ]: Rare: Less than 10%, Accessory: 10%–90%, Core or Almost Core: More than 90%. …”

“…Finally, a comprehensive comparative genomic screen reveals many other peptides, with varied distributions across pneumococcal strains (from rare to core), as well as unique to pneumococcus or shared across streptococcal species [ 27 ]. Many are organized into operons with putative transporters, modification proteins, or immunity proteins.…”

Recent achievements and perspectives for large-scale recombinant production of antimicrobial peptides

“…Advances in genome sequencing and transcriptomics have enabled the identification and development of a large antimicrobial peptide (AMP) library (Rezaei Javan et al 2018). AMPs typically composed of 5-100 amino acids are ubiquitous in nature and present in both prokaryotic and eukaryotic organisms as multipotent components constituting their innate immune defense systems (Ganz 2003;Zasloff 2002).…”