A Mathematical Model of Diel Activity and Long Time Survival in Phototrophic Mixed-Species Subaerial Biofilms.

Subaerial biofilms (SAB) are intricate microbial communities living on terrestrial surfaces, of interest in a variety of contexts including cultural heritage preservation, microbial ecology, biogeochemical cycling, and biotechnology. Here we propose a mathematical model aimed at better understanding the interplay between cyanobacteria and heterotrophic bacteria, common microbial SAB constituents, and their mutual dependence on local environmental conditions. SABs are modeled as thin mixed biofilm-liquid water layers sitting on stone.

Water activity in subaerial microbial biofilms on stone monuments.

Stone monuments can be difficult environments for life, particularly with respect to liquid water access. Nevertheless, microbial communities are found on them with apparent ubiquity. A variety of strategies for access to liquid water have been proposed.

Eicosanoid-Activated PPARα Inhibits NFκB-Dependent Bacterial Clearance During Post-Influenza Superinfection.

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 and resolution of inflammation. CYP450 lipid metabolites are anti-inflammatory lipid mediators that are produced at an excessive level during superinfection potentiating the vulnerability to secondary bacterial infection.

Nitrate Is an Environmental Cue in the Gut for Salmonella enterica Serovar Typhimurium Biofilm Dispersal through Curli Repression and Flagellum Activation via Cyclic-di-GMP Signaling.

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

Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin.

There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit.

A Bead Movement Based Computational Framework for 3-Dimensional Analysis of Biofilm Material Heterogeneity.

Differences in the material properties of bacterial biofilms have been observed in biofilms of different bacterial species, within the same species under different growth conditions and after treatment with matrix modifying molecules. To better quantitate the material properties of 3D biofilms, an experimental and computational workflow was developed and applied to examine differences between Enterococcus faecalis, Salmonella enterica serotype Typhimurium and Escherichia coli biofilms as well as the role of the amyloid curli in confirming rigidity to Enterobacteriaceae biofilms. The spatio-temporal dynamics of 1 µm carboxylate beads in biofilms were tracked in 20 µm 3D biofilms over 20 minutes.

Enhanced eradication of intracellular and biofilm-residing methicillin-resistant Staphylococcus aureus (MRSA) reservoirs with hybrid nanoparticles delivering rifampicin.

Osteomyelitis carries a high risk of recurrence even after extended, aggressive antibiotic therapy. One of the key challenges is to eradicate the reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) inside the host bone cells and their biofilms. Our goal is to develop rifampicin loaded lipid-polymer hybrid nanocarriers (Rf-LPN) and evaluate if they can achieve enhanced rifampicin delivery to eradicate these intracellular and biofilm-residing MRSA.

Development of a New Bead Movement-Based Computational Framework Shows that Bacterial Amyloid Curli Reduces Bead Mobility in Biofilms.

Biofilms exist in complex environments, including the intestinal tract, as a part of the gastrointestinal microbiota. The interaction of planktonic bacteria with biofilms can be influenced by material properties of the biofilm. During previous confocal studies, we observed that amyloid curli-containing serotype Typhimurium and biofilms appeared rigid.

Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing osteomyelitis. The tendency of MRSA to evade standard antibiotic treatment by hiding inside bone cells and biofilms is a major cause of frequent osteomyelitis recurrence. In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA.

Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli.

Bacterial biofilms, especially those associated with implanted medical devices, are difficult to eradicate. Curli amyloid fibers are important components of the biofilms formed by the Enterobacteriaceae family. Here, we show that a human monoclonal antibody with pan-amyloid-binding activity (mAb 3H3) can disrupt biofilms formed by Salmonella enterica serovar Typhimurium in vitro and in vivo.

Protein kinase C-delta inhibition is organ-protective, enhances pathogen clearance, and improves survival in sepsis.

Sepsis is a leading cause of morbidity and mortality in intensive care units. Previously, we identified Protein Kinase C-delta (PKCδ) as an important regulator of the inflammatory response in sepsis. An important issue in development of anti-inflammatory therapeutics is the risk of immunosuppression and inability to effectively clear pathogens.

Cytotoxic Curli Intermediates Form during Biofilm Development.

produce amyloid proteins called curli that are the major proteinaceous component of biofilms. Amyloids are also produced by humans and are associated with diseases such as Alzheimer's. During the multistep process of amyloid formation, monomeric subunits form oligomers, protofibrils, and finally mature fibrils.

Bacteriophage φEf11 ORF28 Endolysin, a Multifunctional Lytic Enzyme with Properties Distinct from All Other Identified Enterococcus faecalis Phage Endolysins.

ϕEf11 is a temperate bacteriophage that infects strains of The ϕEf11 genome, encompassing 65 open reading frames (ORFs), is contained within 42,822 bp of DNA. Within this genome, a module of six lysis-related genes was identified. Based upon sequence homology, one of these six genes, ORF28, was predicted to code for an -acetylmuramoyl-l-alanine amidase endolysin of 46.

Synthesis and biological evaluation of solithromycin analogs against multidrug resistant pathogens.

Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.

Ribosome-Templated Azide-Alkyne Cycloadditions Using Resistant Bacteria as Reaction Vessels: Click Chemistry.

click chemistry has been a powerful method for fragment-based drug design since its discovery in 2002. Recently, we demonstrated that the bacterial ribosome can template the azide-alkyne cycloaddition reaction to expedite the discovery of novel antibiotics. We now report this process can be performed in an antibiotic-resistant bacterial cell.

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms.

The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S.

Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9.

Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies.

Effect of a genetically engineered bacteriophage on Enterococcus faecalis biofilms.

Objective: Enterococcus faecalis is a Gram-positive, facultative anaerobic bacterium that is associated with failed endodontic cases and nosocomial infections. E. faecalis can form biofilms, penetrate dentinal tubules and survive in root canals with scarce nutritional supplies.

Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by In Situ Click Chemistry.

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 the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides.

Bioorganic Investigation of Multicationic Antimicrobials to Combat QAC-Resistant Staphylococcus aureus.

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

Mucin can enhance growth, biofilm formation, and survival of Streptococcus mutans.

Streptococcus mutans is a member of the dental plaque and is the primary causative agent of dental caries. It can survive extended periods of starvation, which may occur in different niches within the oral cavity. We have found that mucin compensated for the absence of amino acids to promote exponential growth and biofilm formation of S.

Bacteria adhere less to barbed monofilament than braided sutures in a contaminated wound model.

Background: Previous studies have found fewer clinical infections in wounds closed with monofilament suture compared with braided suture. Recently, barbed monofilament sutures have shown improved strength and increased timesavings over interrupted braided sutures. However, the adherence of bacteria to barbed monofilament sutures and other commonly used suture materials is unclear.

Community-associated methicillin-resistant Staphylococcus aureus survival on artificial turf substrates.

Objective: Artificial turf has been suggested as a risk factor for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). This is an experimental study looking at survival of CA-MRSA on artificial turf.

Methods: MRSA strain USA-300-0114 was grown as either planktonic cells or biofilms in liquid cultures of beef heart infusion broth overnight at 37 °C.

The pdh operon is expressed in a subpopulation of stationary-phase bacteria and is important for survival of sugar-starved Streptococcus mutans.

Streptococcus mutans is a facultative member of the oral plaque and is associated with dental caries. It is able to survive long periods of sugar starvation. We show here that inactivation of pdhD, putatively encoding a subunit of the pyruvate dehydrogenase complex, impairs survival of both batch cultures and biofilms.