A new quorum‐sensing system (TprA/PhrA) for Streptococcus pneumoniae D39 that regulates a lantibiotic biosynthesis gene cluster

Abstract

The Phr peptides of Bacillus species mediate quorum sensing, but their identification and function in other species of bacteria has not been determined. We have identified a Phr peptide quorum sensing system (TprA/PhrA) that controls the expression of a lantibiotic gene cluster in the Gram-positive human pathogen, Streptococcus pneumoniae. Lantibiotics are highly modified peptides that are part of the bacteriocin family of antimicrobial peptides. We have characterized the basic mechanism for a Phr peptide signaling system in S. pneumoniae and found that it induces expression of the lantibiotic genes when pneumococcal cells are at high density in the presence of galactose, a main sugar of the human nasopharynx, a highly competitive microbial environment. Activity of the Phr peptide system is not seen when pneumococcal cells are grown with glucose, the preferred carbon source and the most prevalent sugar encountered by S. pneumoniae during invasive disease. Thus, the lantibiotic genes are expressed under the control of both cell density signals via the Phr peptide system and nutritional signals from the carbon source present, suggesting that quorum sensing and the lantibiotic machinery may help pneumococcal cells compete for space and resources during colonization of the nasopharynx.

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

“…Production of mutacin I, the Bifidobacterium longum DJO10A lantibiotic and the two component haloduracin from Bacillus halodurans was also only seen on solid media [66,68,69], and it has been proposed that the dense colonization necessary for mutacin I production is reminiscent of a biofilm condition [66]. A putative lantibiotic cluster in Streptococcus pneumoniae has recently been shown to be controlled by quorum sensing, with expression being induced at high cell densities and depending on the carbon source [70]. Alternatively, the mechanism of trypsin may rely on pre-peptide cleavage rather than induction; in vitro biosynthesis of nisin using just nisABC successfully produced active nisin after treatment with trypsin [49].…”

Quorum Sensing in a Methane-Oxidizing Bacterium

“…QS systems often regulate the production of extracellular products (13), such as antibiotics (14,15) and proteases (28). One hypothesis is that this regulation prevents these products from being produced at low cell densities, when the fitness cost for each individual bacterium may outweigh any benefit of the small amount of produced good (12).…”

“…These signal molecules are bound by members of the LuxR family of transcription factors, which control gene expression in an AHL concentration-dependent manner. In many cases, AHLs control the production of extracellular factors, including proteases and antibiotics, which may allow resources to be dedicated to these metabolically expensive products solely under conditions in which the bacterial species has reached a sufficient density to impact its surrounding environment (13)(14)(15).…”

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

“…More recent studies have revealed a distinct signal transduction architecture, where an active form of a secreted peptide is internalized into cells and directly binds a transcription factor from the RRNPP (Rap, Rgg, NprR, PlcR and PrgX) superfamily (Rocha‐Estrada et al ., ). There are multiple RRNPP systems encoded in the pneumococcal pangenome (Bortoni et al ., ; Hoover et al ., ; Kadam et al ., ), and cognate peptides have been identified for two of the regulators (PhrA for TprA and PhrA2 for TprA2) (Hoover et al ., ; Kadam et al ., ). Thus, pneumococcal strains make use of distinct peptide‐induced signal transduction pathways during infection.…”