A novel growth phase‐associated two‐component‐type regulator, Fas ( f ibronectin/fibrinogen binding/haemolytic a ctivity/ s treptokinase regulator), of Streptococcus pyogenes was identified in the M1 genome sequence, based on homologies to histidine protein kinase (HPK) and response regulator (RR) part Staphylococcus aureus Agr pneumoniae Com quorum‐sensing systems. The fas operon, present all 12 tested M serotypes, transcribed as polycystronic message fasBCA ) contained genes encoding two...

Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric is the amyloid curli, which forms highly immunogenic complexes DNA. Infection curli-expressing bacteria or systemic exposure to purified curli-DNA triggers autoimmunity via generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that complexed curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism. First, cross...

Abstract Bacterial biofilms, especially those associated with implanted medical devices, are difficult to eradicate. Curli amyloid fibers important components of the biofilms formed by Enterobacteriaceae family. Here, we show that a human monoclonal antibody pan-amyloid-binding activity (mAb 3H3) can disrupt Salmonella enterica serovar Typhimurium in vitro and vivo. The disrupts biofilm structure, enhancing eradication antibiotics immune cells. In mice, 3H3 injections allow...

Quaternary ammonium compounds (QACs) have historically served as a first line of defense against pathogenic bacteria. Recent reports shown that QAC resistance is increasing at an alarming rate, especially among methicillin-resistant Staphylococcus aureus (MRSA), and preliminary work has suggested the number cations present in scaffold inversely correlates with resistance. Given our interest multiQACs, we initiated multipronged approach to investigate their biofilm eradication properties,...

Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind 50S subunit with nM affinity inhibit protein synthesis blocking passage nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered combinatorial copper-catalyzed click chemistry, was synthesized in situ incubating either E. coli 70S ribosomes or...

Previous studies have found fewer clinical infections in wounds closed with monofilament suture compared braided suture. Recently, barbed sutures shown improved strength and increased timesavings over interrupted sutures. However, the adherence of bacteria to other commonly used materials is unclear.We therefore determined: (1) five types including a suture; (2) ability culture after gentle washing each type; (3) pattern bacterial adherence.We created an experimental contaminated wound model...

Intracellular polysaccharide (IPS) is accumulated by Streptococcus mutans when the bacteria are grown in excess sugar and can contribute toward cariogenicity of S. mutans. Here we show that inactivation glgA gene (SMU1536), encoding a putative glycogen synthase, prevented accumulation IPS. IPS important for persistence batch culture with glucose then starved glucose. The was largely used up within 1 day starvation, yet survival parental strain extended at least 15 days beyond mutant;...

Curli, a major component of the bacterial biofilms in intestinal tract, activates pattern recognition receptors and triggers joint inflammation after infection with Salmonella enterica serovar Typhimurium. The factors that allow S. Typhimurium to disperse from invade epithelium establish successful during acute remain unknown. Here, we studied vitro vivo understand how inflammatory environment regulates switch between multicellular motile gut. We discovered nitrate generated by host is an...

ABSTRACT Enterococcus faecalis is a Gram-positive bacterium and opportunistic pathogen that acquires resistance to wide range of antibiotics by horizontal gene transfer (HGT). The rapid increase multidrug-resistant (MDR) bacteria including MDR E. necessitates the development alternative therapies deeper understanding factors impact HGT. CRISPR-Cas systems provide sequence-specific defense against From previous studies, we know provides anti-plasmid during agar plate biofilm mating in murine...

ABSTRACT Three open reading frames (ORFs) were identified by a genome walking strategy in the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591. These ORFs located between mga core regulon dipeptide permease operon. The deduced amino acid (aa) sequences contained signature indicative lipoprotein (306 aa), an intracellular protein (823 secreted peptide (66 respectively. ORF1 (named Lsp for Streptococcus pyogenes ) ORF2 exhibited high degree homology to lmb /ORF2 genes...

To characterize the structure and microbial content of biofilms found on tracheostomy tubes. determine correlation between patients' clinical condition biofilm content.Prospective observational series.Tracheostomy tubes were collected from patients in both inpatient outpatient setting at an urban academic medical center. Sections evaluated by confocal microscopy bacteria them plated identified. The number colony forming units (CFUs) species present determined a univariate analysis performed...

The emergence of multidrug-resistant pathogenic microorganisms has brought increasing attention to the urgent need for development alternative antimicrobial strategies. One such conventional antibiotics employs lytic enzymes (endolysins) that are produced by bacteriophages in course infection. During infection a bacteriophage, these hydrolyze cell wall peptidoglycan, resulting lysis host cell. However, external endolysin application can result from without. In this study, we have cloned,...

ABSTRACT In Enterococcus faecalis , the peptide cCF10 acts as a pheromone, inducing transfer of conjugative plasmid pCF10 from plasmid-containing donor cells to plasmid-free recipient cells. these studies, it was found that substantial amount associates with envelope producing cell. Pheromone activity detected in both wall and membrane fractions, highest associated wall. Experiments examining effects protease inhibitor treatments either prior or following cell fractionation suggested...

Secondary bacterial infection (superinfection) post influenza is a serious clinical complication often leading to pneumonia and death. Eicosanoids are bioactive lipid mediators that play critical roles in the induction resolution of inflammation. CYP450 metabolites anti-inflammatory produced at an excessive level during superinfection potentiating vulnerability secondary infection. Using Nanostring nCounter technology, we have defined targeted transcriptional response where dampen Toll-like...

The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these Streptococcus mutans, the causative agent of dental caries, most prevalent childhood disease. Carolacton has remarkably specific activity against S. causing acid-mediated cell death during biofilm formation; however, its complex structure limits utility. Herein, we report diverted total synthesis biological evaluation rationally designed library simplified analogs that unveiled three unique...

ABSTRACT In addition to causing fulminant disease, Streptococcus pyogenes may be asymptomatically carried between recurrent episodes of pharyngitis. To better understand streptococcal carriage, we characterized in vitro long-term stationary-phase survival (>4 weeks) S. . When grown sugar-limited Todd-Hewitt broth, cells remained culturable for more than 1 year. Both supplemented with excess glucose and chemically defined medium allowed less week. After 4 weeks at least 10 3 CFU per ml...

ABSTRACT Streptococcus mutans is a member of oral plaque biofilms and considered the major etiological agent dental caries. We have characterized survival S. strain UA159 in both batch cultures biofilms. Bacteria grown chemically defined medium, FMC, containing an excess glucose or sucrose caused pH to decrease 4.0 at entry into stationary phase, they survived for about 3 days. Survival was extended up 11 days when medium contained limiting concentration that depleted by time bacteria...

Streptococcus mutans is a facultative member of the oral plaque and associated with dental caries. It able to survive long periods sugar starvation. We show here that inactivation pdhD, putatively encoding subunit pyruvate dehydrogenase complex, impairs survival both batch cultures biofilms. pdhD downstream genes pdhA, pdhB, pdhC form an operon predominantly transcribed in stationary phase. Analysis fluorescent reporters revealed bimodal expression pattern for pdh promoter, less than 1%...

Enterobacteriaceae produce amyloid proteins called curli that are the major proteinaceous component of biofilms. Amyloids also produced by humans and associated with diseases such as Alzheimer's. During multistep process formation, monomeric subunits form oligomers, protofibrils, finally mature fibrils. Amyloid β oligomers more cytotoxic to cells than Oligomeric intermediates had not been previously detected. We determined turbulence inhibited biofilm formation that, intriguingly, aggregates...