Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae

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.

Frequency-dependent selection in vaccine-associated pneumococcal population dynamics

“…Sequence clusters also varied in their complement of rarer bacteriocin biosynthesis gene clusters, including pneumocyclicin 27 , pneumolancidin 28 , two loci likely regulated by the TprA/PhrA quorum-sensing system 29 , and other putative loci ( Supplementary Fig 1 ). No individual gene cluster replicated the diversity of the blp locus, with sequence variation instead often corresponding to disruptive mutations in bacteriocin structural or biosynthetic genes.…”

Profiling microorganisms in whole saliva of children with and without dental caries

“…and Staphylococcus spp. are known to encode for multiple bacteriocidal molecules that play a role in inter or intraspecies competition, all of which are candidates for competitive interaction in whole saliva (Dawid, Roche, & Weiser, ; Lina et al, ; Lux, Nuhn, Hakenbeck, & Reichmann, ; Maricic, Anderson, Opipari, Yu, & Dawid, ; Otto et al, ). However, these negative associations should be cautiously interpreted, given that the bacteria could still be present, even if not detected.…”

“…The prevalence of S pneumoniae in our sample set may reflect the patient population or biases of the PCR-MS technology. Either way, it suggests that the saliva may play a role (Dawid, Roche, & Weiser, 2007;Lina et al, 2003;Lux, Nuhn, Hakenbeck, & Reichmann, 2007;Maricic, Anderson, Opipari, Yu, & Dawid, 2016;Otto et al, 2001). However, these negative associations should be cautiously interpreted, given that the bacteria could still be present, even if not detected.…”

A novel streptococcal cell–cell communication peptide promotes pneumococcal virulence and biofilm formation

“…The presence of variants raises the question: how do these alleles interact? For signaling and bacteriocidal molecules, specificity has been documented between the signal and the receptor and between the bacteriocins and immunity system, respectively (Dawid et al, 2007;Capra et al, 2010;Maricic et al, 2016). Furthermore, specificity has been observed for bi-functional molecules that play a role in both cooperation and competition (Anderson et al, 2014).…”