Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery widely conserved biosynthetic gene cluster for synthesis thiazole and oxazole heterocycles on peptides. These clusters encode toxin precursor all necessary proteins maturation export. Using heterocycle-forming synthetase from human pathogen Streptococcus pyogenes, demonstrate in vitro reconstitution streptolysin S activity. We provide evidence that enzymes, as predicted our...

Neisseria gonorrhoeae is the bacterium that causes gonorrhea, a major sexually transmitted disease and significant cofactor for human immunodeficiency virus transmission. The retactile N. type IV pilus (Tfp) mediates twitching motility attachment. Using live-cell microscopy, we reveal first time dynamics of by in its natural environment, epithelial cells. Bacteria aggregate into microcolonies on cell surface induce massive remodeling microvillus architecture. Surprisingly, are motile, they...

Phenotypic and functional plasticity of brain immune cells contribute to tissue homeostasis disease. Immune cell is profoundly influenced by microenvironment cues systemic factors. Aging gut microbiota dysbiosis that reshape has not been fully delineated. Using Cellular Indexing Transcriptomes Epitopes sequencing (CITE-seq), we analyze compositional transcriptional changes the landscape in response aging dysbiosis. Discordance between canonical surface-marker-defined types their...

Elastin is a major structural protein found in large blood vessels, lung, ligaments, and skin, imparting the physical properties of extensibility elastic recoil to these tissues. To achieve required durability matrix, elastin monomer, tropoelastin, undergoes ordered assembly into covalently cross-linked, fibrillar polymeric structure. Human tropoelastin consists 34 exons coding for alternating hydrophobic cross-linking domains. Using series well-defined recombinant polypeptides based on...

The human pathogen Streptococcus pyogenes secretes a highly cytolytic toxin known as streptolysin S (SLS). SLS is key virulence determinant and responsible for the β-hemolytic phenotype of these bacteria. Despite over century research, chemical structure remains unknown. Recent experiments have revealed that generated from an inactive precursor peptide undergoes extensive post-translational modification to active form. In this work, we address outstanding questions regarding biosynthetic...

Bacteriocins are peptide-derived molecules produced by bacteria, whose recently-discovered functions include virulence factors and signaling as well their better known roles antibiotics. To date, close to five hundred bacteriocins have been identified classified. Recent discoveries shown that highly diverse widely distributed among bacterial species. Given the heterogeneity of bacteriocin compounds, many tools struggle with identifying novel due vast sequence structural diversity. Many...

Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source promising antibiotic alternatives. However, bacteriocins display diverse mechanisms action, a narrow spectrum activity, and inherent challenges in natural product isolation making vitro verification putative difficult. A subset exert their effects through favorable biophysical interactions with bacterial membrane mediated by charge, hydrophobicity, conformation peptide. We have developed...

ABSTRACT Group A Streptococcus (GAS) is a major human pathogen that causes several invasive diseases including necrotizing fasciitis. The host coagulation cascade initiates fibrin clots to sequester bacteria prevent dissemination into deeper tissues. GAS, especially skin-tropic bacterial strains, utilize specific virulence factors, plasminogen binding M-protein (PAM) and streptokinase (SK), manipulate hemostasis activate cause fibrinolysis clot escape. unresolved question regards the...

The retractile type IV pilus participates in a number of fundamental bacterial processes, including motility, DNA transformation, fruiting body formation and attachment to host cells. Retraction the N. gonorrhoeae requires functional pilT. generates substantial force on its substrate (> 100 pN per retraction event), it has been speculated that epithelial cells sense respond these forces during infection. We provide evidence piliated, Opa non-expressing Neisseria activates stress-responsive...

Through elaboration of its botulinum toxins, Clostridium produces clinical syndromes infant botulism, wound and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. the related foodborne pathogen sporogenes that resembled biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible hallmark β-hemolytic phenotype. Genetic complementation, vitro reconstitution, mass spectral plasmid...

Modularly assembled, antimicrobial peptide capped phage-mimicking nanoparticles are highly biocompatible, rapidly bactericidal, and clear wound infections without the emergence of antibacterial resistance.

The Neisseria type IV pilus promotes bacterial adhesion to host cells. binds CD46, a complement-regulatory glycoprotein present on nucleated human cells (Källström et al., 1997). CD46 mutants with truncated cytoplasmic tails fail support 2001), suggesting that this region of the molecule also plays an important role in infection. Here, we report infection epithelial by piliated gonorrhoeae (GC) leads rapid tyrosine phosphorylation CD46. Studies wild-type and mutant tail fusion constructs...

ABSTRACT Streptococcus pyogenes , or group A (GAS), is a pathogen that causes multitude of human diseases from pharyngitis to severe infections such as toxic shock syndrome and necrotizing fasciitis. One the primary virulence factors produced by GAS peptide toxin streptolysin S (SLS). In addition its well-recognized role cytolysin, recent evidence has indicated SLS may influence host cell signaling pathways at sublytic concentrations during infection. We employed an antibody array-based...

Genomic recombination plays an important role in driving adaptive evolution and population differentiation bacteria. However, controversy exists as to the effects of on diversity differentiation, i.e., is frequent enough sweep through at selected gene loci (gene-specific sweeps), or rate low without interfering genome-wide selective sweeps. Observations supporting either view are sparse. Pathogenic bacteria causing infectious diseases promising candidates provide observations recombination....

Bacterial Peptides:

The cluster of virulence sensor (CovS)/responder (CovR) two-component operon (CovRS) regulates ∼15% the genes Group A Streptococcal pyogenes (GAS) genome. Bacterial clones containing inactivating mutations in covS gene have been isolated from patients with virulent invasive diseases. We report herein an assessment nature and types that can occur both nonvirulent GAS strains, assess whether a attain enhanced through this mechanism. group mice were infected globally-disseminated clonal M1T1...

The first genome sequence of a group A Streptococcus pyogenes serotype M23 (emm23) strain (M23ND), isolated from an invasive human infection, has been completed. this opacity factor-negative (SOF(-)) is composed circular chromosome 1,846,477 bp. Gene profiling showed that contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well 11 pseudogenes. bacterium acquired four large prophage elements, ΦM23ND.1 to ΦM23ND.4, harboring genes encoding streptococcal...

The genome of an invasive skin-tropic strain (AP53) serotype M53 group A Streptococcus pyogenes (GAS) is composed a circular chromosome 1,860,554 bp and carries genetic markers for infection at skin locales, viz, emm gene family pattern D FCT type 3. Through genome-scale comparisons AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal potential basis tropism. differed by ∼30 point mutations from noninvasive (Alab49), 4 which are located...

The increasing frequency of nosocomial infections caused by antibiotic-resistant microorganisms concurrent with the stagnant discovery new classes antibiotics has made development antibacterial agents a critical priority. Our approach is an antibiotic-free strategy drawing inspiration from bacteriophages to combat bacteria. We developed nanoparticle-based system that structurally mimics protein-turret distribution on head structure certain and explored combination different materials...

The bacterial pathogen Group A Streptococcus (GAS) has been shown to induce a variety of human diseases ranging in severity from pharyngitis toxic shock syndrome and necrotizing fasciitis. One the major virulence factors produced by GAS is peptide toxin Streptolysin S (SLS). Though this long recognized as potent cytolysin, recent evidence our lab indicated that SLS-dependent cytotoxicity keratinocytes mediated through inactivation cytoprotective factor Akt1 subsequent activation...

ABSTRACT Streptococcus pyogenes , or group A (GAS), is both a pathogen and an asymptomatic colonizer of human hosts produces large number surface-expressed secreted factors that contribute to variety infection outcomes. The GAS-secreted cysteine protease SpeB has been well studied for its effects on the host; however, despite broad proteolytic activity, studies how this factor utilized in polymicrobial environments are lacking. Here, we various forms evaluate antimicrobial antibiofilm...