scholarly journals Bacteriocin Production by Beta-Hemolytic Streptococci

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 867
Author(s):  
Verena Vogel ◽  
Barbara Spellerberg

Beta-hemolytic streptococci cause a variety of infectious diseases associated with high morbidity and mortality. A key factor for successful infection is host colonization, which can be difficult in a multispecies environment. Secreting bacteriocins can be beneficial during this process. Bacteriocins are small, ribosomally produced, antimicrobial peptides produced by bacteria to inhibit the growth of other, typically closely related, bacteria. In this systematic review, bacteriocin production and regulation of beta-hemolytic streptococci was surveyed. While Streptococcus pyogenes produces eight different bacteriocins (Streptococcin A-FF22/A-M49, Streptin, Salivaricin A, SpbMN, Blp1, Blp2, Streptococcin A-M57), only one bacteriocin of Streptococcus agalactiae (Agalacticin = Nisin P) and one of Streptococcus dysgalactiae subsp. equisimilis (Dysgalacticin) has been described. Expression of class I bacteriocins is regulated by a two-component system, typically with autoinduction by the bacteriocin itself. In contrast, a separate quorum sensing system regulates expression of class II bacteriocins. Both identified class III bacteriocins are plasmid-encoded and regulation has not been elucidated.

2020 ◽  
Author(s):  
Mihnea R. Mangalea ◽  
Bradley R. Borlee

AbstractIn the environment, Burkholderia pseudomallei exists as a saprophyte inhabiting soils and surface waters where denitrification is important for anaerobic respiration. As an opportunistic pathogen, B. pseudomallei transitions from the environment to infect human and animal hosts where respiratory nitrate reduction enables replication in anoxic conditions. We have previously shown that B. pseudomallei responds to nitrate and nitrite in part by inhibiting biofilm formation and altering cyclic di-GMP signaling. Here, we describe the global transcriptomic response to nitrate and nitrite to characterize the nitrosative stress response relative to biofilm inhibition. To better understand the roles of nitrate-sensing in the biofilm inhibitory phenotype of B. pseudomallei, we created in-frame deletions of narX (Bp1026b_I1014) and narL (Bp1026b_I1013), which are adjacent components of the conserved nitrate-sensing two-component system. Through differential expression analysis of RNA-seq data, we observed that key components of the biofilm matrix are downregulated in response to nitrate and nitrite. In addition, several gene loci associated with the stringent response, central metabolism dysregulation, antibiotic tolerance, and pathogenicity determinants were significantly altered in their expression. Some of the most differentially expressed genes were nonribosomal peptide synthases (NRPS) and/or polyketide synthases (PKS) encoding the proteins for the biosynthesis of bactobolin, malleilactone, and syrbactin, in addition to an uncharacterized cryptic NRPS biosynthetic cluster. We also observed reduced expression of ribosomal structural and biogenesis loci, and gene clusters associated with translation and DNA replication, indicating modulation of growth rate and metabolism under nitrosative stress conditions. The differences in expression observed under nitrosative stress were reversed in narX and narL mutants, suggesting that nitrate sensing is an important checkpoint for regulating the diverse metabolic changes occurring in the biofilm inhibitory phenotype. Moreover, in a macrophage model of infection, narX and narL mutants were attenuated in intracellular replication, suggesting that nitrate sensing is important for host survival.Author SummaryBurkholderia pseudomallei is a saprophytic bacterium inhabiting soils and surface waters throughout the tropics causing severe disease in humans and animals. Environmental signals such as the accumulation of inorganic ions mediates the biofilm forming capabilities and survival of B. pseudomallei. In particular, nitrate metabolism inhibits B. pseudomallei biofilm formation through complex regulatory cascades that relay environmental cues to intracellular second messengers that modulate bacterial physiology. Nitrates are common environmental contaminants derived from artificial fertilizers and byproducts of animal wastes that can be readily reduced by bacteria capable of denitrification. In B. pseudomallei 1026b, biofilm dynamics are in part regulated by a gene pathway involved in nitrate sensing, metabolism, and transport. This study investigated the role of a two-component nitrate sensing system, NarX-NarL, in regulating gene expression, biofilm formation, and cellular invasion. Global gene expression analyses in the wild type, as compared to Δ narX and Δ narL mutant strains with nitrate or nitrite implicate the NarX-NarL system in the regulation of biofilm components as well as B. pseudomallei host-associated survival. This study characterizes a conserved nitrate sensing system that is important in environmental and host-associated contexts and aims to bridge a gap between these two important B. pseudomallei lifestyles.


2005 ◽  
Vol 28 (11) ◽  
pp. 1069-1078 ◽  
Author(s):  
V. Vadyvaloo ◽  
M. Otto

Staphylococcus epidermidis is an opportunistic pathogen associated with foreign body infections and nosocomial sepsis. The pathogenicity of S. epidermidis is mostly due to its ability to colonize indwelling polymeric devices and form a thick, multilayered biofilm. Biofilm formation is a major problem in treating S. epidermidis infection as biofilms provide significant resistance to antibiotics and to components of the innate host defenses. Various cell surface associated bacterial factors play a role in adherence and accumulation of the biofilm such as the polysaccharide intercellular adhesin and the autolysin AtlE. Furthermore, recent studies have shown that global regulators such as the agr quorum sensing system, the transcriptional regulator sarA and the alternative sigma factor sigB have an important function in the regulation of biofilm formation. Understanding the many complex mechanisms involved in biofilm formation is a key factor in the search for new anti-staphylococcal therapeutics.


1999 ◽  
Vol 181 (20) ◽  
pp. 6264-6270 ◽  
Author(s):  
Ronda M. Anderson ◽  
Chad A. Zimprich ◽  
Lynn Rust

ABSTRACT Pseudomonas aeruginosa LasB elastase gene (lasB) transcription is controlled by the two-component quorum-sensing system of LasR, and the autoinducer, 3OC12-HSL (N-3-[oxododecanoyl]homoserine lactone). LasR and 3OC12-HSL-mediated lasBactivation requires a functional operator sequence (OP1) in thelasB promoter region. Optimal activation oflasB, however, requires a second sequence of 70% identity to OP1, named OP2, located 43 bp upstream of OP1. In this study, we used sequence substitutions and insertion mutations inlasBp-lacZ fusion plasmids to explore the role of OP2 in lasB activation. Our results demonstrate that (i) OP1 and OP2 synergistically mediate lasB activation; (ii) OP2, like OP1, responds to LasR and 3OC12-HSL; and (iii) the putative autoinducer-binding domain of LasR is not required for synergistic activation from OP1 and OP2.


mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexis Proutière ◽  
Laurence du Merle ◽  
Bruno Périchon ◽  
Hugo Varet ◽  
Myriam Gominet ◽  
...  

ABSTRACT Bacteriocins are natural antimicrobial peptides produced by bacteria to kill closely related competitors. The opportunistic pathogen Streptococcus gallolyticus subsp. gallolyticus was recently shown to outcompete commensal enterococci of the murine microbiota under tumoral conditions thanks to the production of a two-peptide bacteriocin named gallocin. Here, we identified four genes involved in the regulatory control of gallocin in S. gallolyticus subsp. gallolyticus UCN34 that encode a histidine kinase/response regulator two-component system (BlpH/BlpR), a secreted peptide (GSP [gallocin-stimulating peptide]), and a putative regulator of unknown function (BlpS). While BlpR is a typical 243-amino-acid (aa) response regulator possessing a phospho-receiver domain and a LytTR DNA-binding domain, BlpS is a 108-aa protein containing only a LytTR domain. Our results showed that the secreted peptide GSP activates the dedicated two-component system BlpH/BlpR to induce gallocin transcription. A genome-wide transcriptome analysis indicates that this regulatory system (GSP-BlpH/BlpR) is specific for bacteriocin production. Importantly, as opposed to BlpR, BlpS was shown to repress gallocin gene transcription. A conserved operator DNA sequence of 30 bp was found in all promoter regions regulated by BlpR and BlpS. Electrophoretic mobility shift assays (EMSA) and footprint assays showed direct and specific binding of BlpS and BlpR to various regulated promoter regions in a dose-dependent manner on this conserved sequence. Gallocin expression appears to be tightly controlled in S. gallolyticus subsp. gallolyticus by quorum sensing and antagonistic activity of 2 LytTR-containing proteins. Competition experiments in gut microbiota medium and 5% CO2 to mimic intestinal conditions demonstrate that gallocin is functional under these in vivo-like conditions. IMPORTANCE Streptococcus gallolyticus subsp. gallolyticus, formerly known as Streptococcus bovis biotype I, is an opportunistic pathogen causing septicemia and endocarditis in the elderly often associated with asymptomatic colonic neoplasia. Recent studies indicate that S. gallolyticus subsp. gallolyticus is both a driver and a passenger of colorectal cancer. We previously showed that S. gallolyticus subsp. gallolyticus produces a bacteriocin, termed gallocin, enabling colonization of the colon under tumoral conditions by outcompeting commensal members of the murine microbiota such as Enterococcus faecalis. Here, we identified and extensively characterized a four-component system that regulates gallocin production. Gallocin gene transcription is activated by a secreted peptide pheromone (GSP) and a two-component signal transduction system composed of a transmembrane histidine kinase receptor (BlpH) and a cytosolic response regulator (BlpR). Finally, a DNA-binding protein (BlpS) was found to repress gallocin genes transcription, likely by antagonizing BlpR. Understanding gallocin regulation is crucial to prevent S. gallolyticus subsp. gallolyticus colon colonization under tumoral conditions.


2001 ◽  
Vol 183 (2) ◽  
pp. 451-460 ◽  
Author(s):  
P. Tortosa ◽  
L. Logsdon ◽  
B. Kraigher ◽  
Y. Itoh ◽  
I. Mandic-Mulec ◽  
...  

ABSTRACT A quorum-sensing mechanism involving the pheromone ComX and the ComP-ComA two-component system controls natural competence inBacillus subtilis. ComX is expressed as a cytoplasmic inactive precursor that is released into the extracellular medium as a cleaved, modified decapeptide. This process requires the product ofcomQ. In the presence of ComX, the membrane-localized ComP histidine kinase activates the response regulator ComA. We compared the sequences of the quorum-sensing genes from four closely related bacilli, and we report extensive genetic polymorphism extending throughcomQ, comX, and the 5′ two-thirds ofcomP. This part of ComP encodes the membrane-localized and linker domains of the sensor protein. We also determined the sequences of the comX genes of four additional wild-type bacilli and tested the in vivo activities of all eight pheromones on isogenic strains containing four different ComP receptor proteins. A striking pattern of specificity was discovered, providing strong evidence that the pheromone contacts ComP directly. Furthermore, we show that coexpression of comQ and comX inEscherichia coli leads to the production of active pheromone in the medium, demonstrating that comQ is the only dedicated protein required for the processing, modification, and release of active competence pheromone. Some of the implications of these findings for the evolution and the mechanism of the quorum-sensing system are discussed.


2020 ◽  
Author(s):  
Alexis Proutière ◽  
Bruno Périchon ◽  
Laurence du Merle ◽  
Hugo Varet ◽  
Patrick Trieu-Cuot ◽  
...  

AbstractBacteriocins are natural antimicrobial peptides produced by bacteria to kill closely related competitors. The opportunistic pathogen Streptococcus gallolyticus (Sgg) was recently shown to outcompete commensal enterococci of the murine microbiota in tumoral conditions thanks to the production of a two-peptide bacteriocin named gallocin. We here identified 4 genes involved in the regulatory control of gallocin in Sgg UCN34, respectively encoding a histidine kinase/response regulator two-component system (BlpH/BlpR), a secreted peptide (GSP), and a putative regulator of unknown function (BlpS). While BlpR is a typical 243-aa response regulator possessing a phospho-receiver domain and a LytTR DNA-binding domain, BlpS is a 108-aa protein containing only a LytTR domain. Our results showed that the secreted peptide GSP activates the dedicated two-component system BlpH/BlpR to induce gallocin transcription. A genome-wide transcriptome analysis indicates that this regulatory system (GSP-BlpH/BlpR) is highly specific for bacteriocin production. Importantly, as opposed to BlpR, BlpS was shown to repress gallocin gene transcription. A conserved operator DNA sequence of 30-bp was found in all promoter regions regulated by BlpR and BlpS. EMSA assays showed direct and specific binding of the two gallocin regulators to various regulated promoter regions in a dose dependent manner. Gallocin expression appears tightly controlled in Sgg by quorum sensing and antagonistic activity of 2 LytTR-containing proteins.SignificanceStreptococcus gallolyticus (Sgg), formely known as S. bovis biotype I, is an opportunistic pathogen causing septicemia and endocarditis in the elderly often associated with asymptomatic colonic neoplasia. We previously showed that Sgg produces a bacteriocin, termed gallocin, enabling colonization of the colon in tumoral conditions by outcompeting commensal members of the gut. Here we characterized a 4-component regulatory system that regulates gallocin transcription, which is activated by the response regulator BlpR. BlpR itself is activated by a quorum sensing peptide GSP and a dedicated histidine kinase BlpH. Interestingly, BlpS, a small DNA-binding protein co-transcribed with BlpR was found to repress gallocin genes transcription, likely by antagonizing BlpR. Understanding gallocin regulation is crucial to prevent Sgg colon colonization in tumoral conditions.


2015 ◽  
Vol 198 (2) ◽  
pp. 321-331 ◽  
Author(s):  
Lauren Davey ◽  
Scott A. Halperin ◽  
Song F. Lee

ABSTRACTStreptococcus gordoniiis a commensal inhabitant of the human oral cavity. To maintain its presence as a major component of oral biofilms,S. gordoniisecretes inhibitory molecules such as hydrogen peroxide and bacteriocins to inhibit competitors.S. gordoniiproduces two nonmodified bacteriocins (i.e., Sth1and Sth2) that are regulated by the Com two-component regulatory system, which also regulates genetic competence. Previously we found that the thiol-disulfide oxidoreductase SdbA was required for bacteriocin activity; however, the role of SdbA in Com signaling was not clear. Here we demonstrate that ΔsdbAmutants lacked bacteriocin activity because the bacteriocin genesthAwas strongly repressed and the peptides were not secreted. Addition of synthetic competence-stimulating peptide to the medium reversed the phenotype, indicating that the Com pathway was functional but was not activated in the ΔsdbAmutant. Repression of bacteriocin production was mediated by the CiaRH two-component system, which was strongly upregulated in the ΔsdbAmutant, and inactivation of CiaRH restored bacteriocin production. The CiaRH-induced protease DegP was also upregulated in the ΔsdbAmutant, although it was not required for inhibition of bacteriocin production. This establishes CiaRH as a regulator of Sth bacteriocin activity and links the CiaRH and Com systems inS. gordonii. It also suggests that either SdbA or one of its substrates is an important factor in regulating activation of the CiaRH system.IMPORTANCEStreptococcus gordoniiis a noncariogenic colonizer of the human oral cavity. To be competitive in the oral biofilm,S. gordoniisecretes antimicrobial peptides called bacteriocins, which inhibit closely related species. Our previous data showed that mutation of the disulfide oxidoreductase SdbA abolished bacteriocin production. In this study, we show that mutation of SdbA generates a signal that upregulates the CiaRH two-component system, which in turn downregulates a second two-component system, Com, which regulates bacteriocin expression. Our data show that these systems are also linked inS. gordonii, and the data reveal that the cell's ability to form disulfide bonds is sensed by the CiaRH system.


2021 ◽  
Vol 9 (10) ◽  
pp. 2082
Author(s):  
Olga Tsaplina ◽  
Inessa Khmel ◽  
Yulia Zaitseva ◽  
Sofia Khaitlina

The bacteria Serratia proteamaculans 94 have a LuxI/LuxR type QS system consisting of AHL synthase SprI and the regulatory receptor SprR. We have previously shown that inactivation of the AHL synthase sprI gene resulted in an increase in the invasive activity of S. proteamaculans correlated with an increased bacterial adhesion. In the present work, the effects of inactivation of the S. proteamaculans receptor SprR are studied. Our results show that inactivation of the receptor sprR gene leads to an increase in bacterial invasion without any increase in their adhesion. On the other hand, inactivation of the sprR gene increases the activity of the extracellular protease serralysin. Inactivation of the QS system does not affect the activity of the pore-forming toxin ShlA and prevents the ShlA activation under conditions of a limited concentration of iron ions typical of the human body. While the wild type strain shows increased invasion in the iron-depleted medium, deletion of its QS system leads to a decrease in host cell invasion, which is nevertheless similar to the level of the wild type S. proteamaculans grown in the iron-rich medium. Thus, inactivation of either of the two component of the S. proteamaculans LuxI/LuxR-type QS system leads to an increase in the invasive activity of these bacteria through different mechanisms and prevents invasion under the iron-limited conditions.


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