scholarly journals An intramembrane sensory circuit monitors sortase A–mediated processing of streptococcal adhesins

2019 ◽  
Vol 12 (580) ◽  
pp. eaas9941 ◽  
Author(s):  
Jeffrey W. Hall ◽  
Bruno P. Lima ◽  
Gaetan G. Herbomel ◽  
Tata Gopinath ◽  
LeAnna McDonald ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Biofilm Formation ◽  
Response Regulator ◽  
Sortase A ◽  
Gram Positive Bacteria ◽  
Regulatory Circuit ◽  
Bacterial Adhesins ◽  
Genes Encoding ◽  
Quality Control Mechanism ◽  
Cognate Response Regulator

Bacterial adhesins mediate adhesion to substrates and biofilm formation. Adhesins of the LPXTG family are posttranslationally processed by the cell membrane–localized peptidase sortase A, which cleaves the LPXTG motif. This generates a short C-terminal peptide (C-pep) that remains in the cell membrane, whereas the mature adhesin is incorporated into the cell wall. Genes encoding adhesins of the oral bacteriumStreptococcus gordoniiwere differentially expressed depending on whether the bacteria were isolated from saliva or dental plaque and appeared to be coordinately regulated. Deletion ofsspAandsspB (sspAB), both of which encode LPXTG-containing adhesins, unexpectedly enhanced adhesion and biofilm formation. C-peps produced from a model LPXTG-containing adhesin localized to the cell membrane and bound to and inhibited the intramembrane sensor histidine kinase SGO_1180, thus preventing activation of the cognate response regulator SGO_1181. The absence of SspAB C-peps induced the expression of thescaCBAoperon encoding the lipoprotein adhesin ScaA, which was sufficient to preserve and even enhance biofilm formation. This C-pep–driven regulatory circuit also exists in pathogenic streptococci and is likely conserved among Gram-positive bacteria. This quality control mechanism ensures that the bacteria can form biofilms under diverse environmental conditions and may play a role in optimizing adhesion and biofilm formation.

scholarly journals Photo sensing and quorum sensing are integrated to control bacterial group behaviors

2019 ◽  
Author(s):  
Sampriti Mukherjee ◽  
Matthew Jemielita ◽  
Vasiliki Stergioula ◽  
Mikhail Tikhonov ◽  
Bonnie L. Bassler
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Response Regulator ◽  
Sensory Information ◽  
Virulence Gene ◽  
Component System ◽  
Virulence Gene Expression ◽  
Bacterial Phyla ◽  
Expression Of Genes ◽  
Genes Encoding

ABSTRACTPseudomonas aeruginosa transitions between the free-swimming state and the sessile biofilm mode during its pathogenic lifestyle. We show that quorum sensing represses P. aeruginosa biofilm formation and virulence by activating expression of genes encoding the KinB-AlgB two-component system. Phospho-AlgB represses biofilm and virulence genes, while KinB dephosphorylates, and thereby, inactivates AlgB. We discover that the photoreceptor BphP is the kinase that, in response to light, phosphorylates and activates AlgB. Indeed, exposing P. aeruginosa to light represses biofilm formation and virulence gene expression. To our knowledge, P. aeruginosa was not previously known to detect light. The KinB-AlgB-BphP module is present in all Pseudomonads, and we demonstrate that AlgB is the cognate response regulator for BphP in diverse bacterial phyla. We propose that KinB-AlgB-BphP constitutes a “three-component” system and AlgB is the node at which varied sensory information is integrated. This study sets the stage for light-mediated control of P. aeruginosa infectivity.

scholarly journals In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation

2020 ◽  
Vol 21 (22) ◽  
pp. 8601
Author(s):  
Kishore Reddy Venkata Thappeta ◽  
Li Na Zhao ◽  
Choy Eng Nge ◽  
Sharon Crasta ◽  
Chung Yan Leong ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Natural Compound ◽  
Microbial Growth ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Sortase A ◽  
Compound Library ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Mammalian Toxicity

Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.

scholarly journals The Sodium-Driven Flagellar Motor Controls Exopolysaccharide Expression in Vibrio cholerae

2004 ◽  
Vol 186 (15) ◽  
pp. 4864-4874 ◽  
Author(s):  
Crystal M. Lauriano ◽  
Chandradipa Ghosh ◽  
Nidia E. Correa ◽  
Karl E. Klose
Keyword(s):  
Vibrio Cholerae ◽  
Gene Transcription ◽  
Biofilm Formation ◽  
Diarrheal Disease ◽  
Response Regulator ◽  
Gene Clusters ◽  
Signaling Cascade ◽  
Genes Encoding ◽  
Life Threatening

ABSTRACT Vibrio cholerae causes the life-threatening diarrheal disease cholera. This organism persists in aquatic environments in areas of endemicity, and it is believed that the ability of the bacteria to form biofilms in the environment contributes to their persistence. Expression of an exopolysaccharide (EPS), encoded by two vps gene clusters, is essential for biofilm formation and causes a rugose colonial phenotype. We previously reported that the lack of a flagellum induces V. cholerae EPS expression. To uncover the signaling pathway that links the lack of a flagellum to EPS expression, we introduced into a rugose flaA strain second-site mutations that would cause reversion back to the smooth phenotype. Interestingly, mutation of the genes encoding the sodium-driven motor (mot) in a nonflagellated strain reduces EPS expression, biofilm formation, and vps gene transcription, as does the addition of phenamil, which specifically inhibits the sodium-driven motor. Mutation of vpsR, which encodes a response regulator, also reduces EPS expression, biofilm formation, and vps gene transcription in nonflagellated cells. Complementation of a vpsR strain with a constitutive vpsR allele likely to mimic the phosphorylated state (D59E) restores EPS expression and biofilm formation, while complementation with an allele predicted to remain unphosphorylated (D59A) does not. Our results demonstrate the involvement of the sodium-driven motor and suggest the involvement of phospho-VpsR in the signaling cascade that induces EPS expression. A nonflagellated strain expressing EPS is defective for intestinal colonization in the suckling mouse model of cholera and expresses reduced amounts of cholera toxin and toxin-coregulated pili in vitro. Wild-type levels of virulence factor expression and colonization could be restored by a second mutation within the vps gene cluster that eliminated EPS biosynthesis. These results demonstrate a complex relationship between the flagellum-dependent EPS signaling cascade and virulence.

scholarly journals Salivaricin D, a Novel Intrinsically Trypsin-Resistant Lantibiotic from Streptococcus salivarius 5M6c Isolated from a Healthy Infant

2011 ◽  
Vol 78 (2) ◽  
pp. 402-410 ◽  
Author(s):  
Dagim Jirata Birri ◽  
Dag Anders Brede ◽  
Ingolf F. Nes
Keyword(s):  
Abc Transporters ◽  
Response Regulator ◽  
Probiotic Bacterium ◽  
Streptococcus Salivarius ◽  
Human Pathogens ◽  
Gene Encoding ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Genes Encoding ◽  
Immunity Function

ABSTRACTIn this work, we purified and characterized a newly identified lantibiotic (salivaricin D) fromStreptococcus salivarius5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogensStreptococcus pyogenesandStreptococcus pneumoniae. Thus,Streptococcus salivarius5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium.

scholarly journals Exposure of a 23F Serotype Strain ofStreptococcus pneumoniaeto Cigarette Smoke Condensate Is Associated with Selective Upregulation of Genes Encoding the Two-Component Regulatory System 11 (TCS11)

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Riana Cockeran ◽  
Jenny A. Herbert ◽  
Timothy J. Mitchell ◽  
Thérèse Dix-Peek ◽  
Caroline Dickens ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Response Regulator ◽  
Expression Profiles ◽  
Regulatory System ◽  
Cigarette Smoke Condensate ◽  
Genome Expression ◽  
Two Component ◽  
Genes Encoding ◽  
Whole Genome Expression ◽  
Cognate Response Regulator

Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160 μg/mL) for 15 and 60 min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant (P<0.014–0.0006) upregulation of the genes encoding the two-component regulatory system 11 (TCS11), consisting of the sensor kinase,hk11, and its cognate response regulator,rr11, in the setting of increased biofilm formation. These effects of cigarette smoke on the pneumococcus may contribute to colonization of the airways by this microbial pathogen.

scholarly journals Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction

2015 ◽  
Vol 197 (17) ◽  
pp. 2867-2878 ◽  
Author(s):  
Xue-Xian Zhang ◽  
Jonathan C. Gauntlett ◽  
Darby G. Oldenburg ◽  
Gregory M. Cook ◽  
Paul B. Rainey
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Nutrient Acquisition ◽  
Coupled Processes ◽  
Sensor Kinase ◽  
Unique Type ◽  
Content Type ◽  
Genes Encoding ◽  
Interdomain Interactions ◽  
Cognate Response Regulator

ABSTRACTCbrA is an atypical sensor kinase found inPseudomonas. The autokinase domain is connected to a putative transporter of the sodium/solute symporter family (SSSF). CbrA functions together with its cognate response regulator, CbrB, and plays an important role in nutrient acquisition, including regulation ofhutgenes for the utilization of histidine and its derivative, urocanate. Here we report on the findings of a genetic and biochemical analysis of CbrA with a focus on the function of the putative transporter domain. The work was initiated with mutagenesis of histidine uptake-proficient strains to identify histidine-specific transport genes located outside thehutoperon. Genes encoding transporters were not identified, but mutations were repeatedly found incbrA. This, coupled with the findings of [3H]histidine transport assays and further mutagenesis, implicated CbrA in histidine uptake. In addition, mutations in different regions of the SSSF domain abolished signal transduction. Site-specific mutations were made at four conserved residues: W55 and G172 (SSSF domain), H766 (H box), and N876 (N box). The mutations W55G, G172H, and N876G compromised histidine transport but had minimal effects on signal transduction. The H766G mutation abolished both transport and signal transduction, but the capacity to transport histidine was restored upon complementation with a transport-defective allele of CbrA, most likely due to interdomain interactions. Our combined data implicate the SSSF domain of CbrA in histidine transport and suggest that transport is coupled to signal transduction.IMPORTANCENutrient acquisition in bacteria typically involves membrane-bound sensors that, via cognate response regulators, determine the activity of specific transporters. However, nutrient perception and uptake are often coupled processes. Thus, from a physiological perspective, it would make sense for systems that couple the process of signaling and transport within a single protein and where transport is itself the stimulus that precipitates signal transduction to have evolved. The CbrA regulator inPseudomonasrepresents a unique type of sensor kinase whose autokinase domain is connected to a transporter domain. We present genetic and biochemical evidence that suggests that CbrA plays a dual role in histidine uptake and sensing and that transport is dependent on signal transduction.

Specific Inhibitors of Bacterial Adhesion: Observations From the Study of Gram-Positive Bacteria that Initiate Biofilm Formation on the Tooth Surface

1997 ◽  
Vol 11 (1) ◽  
pp. 168-175 ◽  
Author(s):  
J.O. Cisar ◽  
Y. Takahashi ◽  
S. Ruhl ◽  
J.A. Donkersloot ◽  
A.L. Sandberg
Keyword(s):  
Structural Design ◽  
Bacterial Adhesion ◽  
Biofilm Formation ◽  
Tooth Surface ◽  
Viridans Streptococci ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Bacterial Adhesins ◽  
Potential Inhibitors ◽  
Secretory Antibodies

Oral surfaces are bathed in secretory antibodies and other salivary macromolecules that are potential inhibitors of specific microbial adhesion. Indigenous Gram-positive bacteria that colonize teeth, including viridans streptococci and actinomyces, may avoid inhibition of adhesion by host secretory molecules through various strategies that involve the structural design and binding properties of bacterial adhesins and receptors. Further studies to define the interactions of these molecules within the host environment may suggest novel approaches for the control of oral biofilm formation.

scholarly journals Genome-Wide Mapping Reveals Complex Regulatory Activities of BfmR in Pseudomonas aeruginosa

2021 ◽  
Vol 9 (3) ◽  
pp. 485
Author(s):  
Ke Fan ◽  
Qiao Cao ◽  
Lefu Lan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chromatin Immunoprecipitation ◽  
Biofilm Formation ◽  
High Throughput Sequencing ◽  
Response Regulator ◽  
Cellular Functions ◽  
Genome Wide ◽  
Component Systems ◽  
Genes Encoding ◽  
Two Component Systems

BfmR is a response regulator that modulates diverse pathogenic phenotypes and induces an acute-to-chronic virulence switch in Pseudomonas aeruginosa, an important human pathogen causing serious nosocomial infections. However, the mechanisms of action of BfmR remain largely unknown. Here, using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we showed that 174 chromosomal regions of P. aeruginosa MPAO1 genome were highly enriched by coimmunoprecipitation with a C-terminal Flag-tagged BfmR. Integration of these data with global transcriptome analyses revealed that 172 genes in 106 predicted transcription units are potential targets for BfmR. We determined that BfmR binds to and modulates the promoter activity of genes encoding transcriptional regulators CzcR, ExsA, and PhoB. Intriguingly, BfmR bound to the promoters of a number of genes belong to either CzcR or PhoB regulon, or both, indicating that CzcRS and PhoBR two-component systems (TCSs) deeply feed into the BfmR-mediated regulatory network. In addition, we demonstrated that phoB is required for BfmR to promote the biofilm formation by P. aeruginosa. These results delineate the direct BfmR regulon and exemplify the complexity of BfmR-mediated regulation of cellular functions in P. aeruginosa.

scholarly journals Identification of the Three Genes Involved in Controlling Production of a Phytotoxin Tropolone in Burkholderia plantarii

2016 ◽  
Vol 198 (11) ◽  
pp. 1604-1609 ◽  
Author(s):  
Shunpei Miwa ◽  
Eri Kihira ◽  
Akinori Yoshioka ◽  
Kaoru Nakasone ◽  
Sho Okamoto ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Response Regulator ◽  
Rice Seedling ◽  
Seedling Blight ◽  
Response Regulators ◽  
Two Component System ◽  
Content Type ◽  
Bacterial Signal Transduction ◽  
Genes Encoding ◽  
Cognate Response Regulator

ABSTRACTTropolone, a phytotoxin produced byBurkholderia plantarii, causes rice seedling blight. To identify genes involved in tropolone synthesis, we systematically constructed mutations in the genes encoding 55 histidine kinases and 72 response regulators. From the resulting defective strains, we isolated three mutants, KE1, KE2, and KE3, in which tropolone production was repressed. The deleted genes of these mutants were namedtroR1,troK, andtroR2, respectively. The mutant strains did not cause rice seedling blight, and complementation experiments indicated that TroR1, TroK, and TroR2 were involved in the synthesis of tropolone inB. plantarii. However, tropolone synthesis was repressed in the TroR1 D52A, TroK H253A, and TroR2 D46A site-directed mutants. These results suggest that the putative sensor kinase (TroK) and two response regulators (TroR1 and TroR2) control the production of tropolone inB. plantarii.IMPORTANCEA two-component system is normally composed of a sensor histidine kinase (HK) and a cognate response regulator (RR) pair. In this study, HK (TroK) and two RRs (TroR1 and TroR2) were found to be involved in controlling tropolone production inB. plantarii. These three genes may be part of a bacterial signal transduction network. Such networks are thought to exist in other bacteria to regulate phytotoxin production, as well as environmental adaptation and signal transduction.

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