A5029651247- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Antibiotic Resistance in Bacteria
- Antimicrobial Peptides and Activities
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Legionella and Acanthamoeba research
- Health and Medical Research Impacts
- Lipid Membrane Structure and Behavior
- Biochemical and Structural Characterization
- Innovations in Medical Education
- Diversity and Career in Medicine
- Cystic Fibrosis Research Advances
- Yersinia bacterium, plague, ectoparasites research
- Genomics and Phylogenetic Studies
- Nosocomial Infections in ICU
- Evolution and Genetic Dynamics
- Probiotics and Fermented Foods
- Streptococcal Infections and Treatments
- Escherichia coli research studies
- Barrier Structure and Function Studies
- Blood donation and transfusion practices
Yale University
2016-2025
Microbial ID (United States)
2025
Public Health Dayton & Montgomery County
2024
Yale New Haven Hospital
2020
Office of Infectious Diseases
2007
University of California, San Francisco
2000-2003
Rockefeller University
1993-1994
Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in immunocompromised individuals. P. employs type III secretion system to inject effector molecules into the cytoplasm of host cell. This interaction with cell leads inflammatory responses eventually result death. We show infection macrophages results activation caspase-1 an IPAF-dependent, but flagellin-independent, manner. Macrophages deficient IPAF or were markedly resistant aeruginosa–induced death...
ABSTRACT FlhF is a signal recognition particle-like protein present in monotrichous bacteria. The loss of various bacteria results decreased transcription class II, III, or IV flagellar genes, leads to diminished absent motility, and the assembly flagella at nonpolar locations on cell surface. In this work, we demonstrate that defective swimming swarming motility Pseudomonas aeruginosa . localizes pole; absence FlhF, occurs but no longer restricted pole. Δ flhF swim lower velocities than...
Summary Type IV pili (Tfp) are polar surface structures of Pseudomonas aeruginosa required for twitching motility, biofilm formation and adherence. One protein the assembly tfp is FimX, which possesses both GGDEF EAL domains characteristic diguanylate cyclases phosphodiesterases respectively. In this work we demonstrate that FimX has phosphodiesterase activity towards bis‐(3′‐5′)‐cyclic dimeric guanosine monophosphate (c‐di‐GMP), but does not show cyclase activity. Instead, imperfect domain...
ABSTRACT Pseudomonas aeruginosa exhibits swarming motility on 0.5 to 1% agar plates in the presence of specific carbon and nitrogen sources. We have found that PAO1 double mutants expressing neither flagella nor type IV pili ( fliC pilA ) display sliding under same conditions. Sliding was inhibited when pilus expression restored; like motility, it also decreased absence rhamnolipid surfactant production. Transposon insertions gacA gacS increased restored tendril formation spreading colonies,...
NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]–containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory are that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin the inner rod needle proteins of type III secretion systems (T3SSs). Despite strong biochemical evidence implicating detection ligands, genetic has been lacking. Here we report use CRISPR/Cas9 generate...
Aspergillus fumigatus forms ubiquitous airborne conidia that humans inhale on a daily basis. Although respiratory fungal infection activates the adaptor proteins CARD9 and MyD88 via C-type lectin, Toll-like, interleukin-1 family receptor signals, defining temporal spatial pattern of MyD88- CARD9-coupled signals in immune activation clearance has been difficult to achieve. Herein, we demonstrate act two discrete phases cellular compartments direct chemokine- neutrophil-dependent host defense....
Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa can initially attach surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached express structures, such as Type IV pili, behaviors, including twitching motility initiation. P. lack the GTPase FlhF assemble...
Pseudomonas aeruginosa, an important nosocomial pathogen of humans, expresses a type III secretion system that is required for virulence. Previous studies demonstrated the lung-virulent strain PA103 has capacity to be either cytotoxic or invasive. Analyses mutants suggest delivers negative regulator invasion, anti-internalization factor, host cells via system. In this work we show secreted protein ExoT inhibits internalization by polarized epithelial (Madin-Darby canine kidney cells) and...
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen capable of acutely infecting or persistently colonizing susceptible hosts. P. colonizes surfaces in vitro by either biofilm formation swarming motility. The choice behaviour influenced the physical properties surface and specific nutrient availability, subject to regulatory networks that also govern type 2 3 protein secretion. Biofilm clinical isolates has been well-studied. However, human not extensively analysed. We...
Type IVa pili (T4P) are bacterial surface structures that enable motility, adhesion, biofilm formation and virulence. T4P assembled by nanomachines span the cell envelope. Cycles of assembly retraction, powered ATPases PilB PilT, allow bacteria to attach pull themselves along surfaces, so-called "twitching motility". These opposing ATPase activities must be coordinated limited one pole for show directional movement. How this occurs is still incompletely understood. Herein, we c-di-GMP...
Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce salt-retaining steroid hormone aldosterone and cause millions cases severe hypertension worldwide. Either 2 somatic mutations in potassium channel KCNJ5 (G151R L168R, hereafter referred to as KCNJ5MUT) adrenocortical cells account for half APAs These alter selectivity allow abnormal Na+ conductance, resulting membrane depolarization, calcium influx, production, cell proliferation. Because...
Summary The type III secretion system (TTSS) of Pseudomonas aeruginosa is induced by contact with eukaryotic cells and growth in low‐calcium media. We have identified a protein, RtsM, that necessary for expression the TTSS genes P. . RtsM possesses both histidine kinase response regulator domains common to two‐component signalling proteins, as well large predicted periplasmic domain seven transmembrane domains. Deletion rtsM resulted defect production effectors. Northern blot analysis...
Oxidative stress is one of the main challenges bacteria must cope with during infection. Here, we identify a new oxidative sensing and response ospR (oxidative pigment production Regulator) gene in Pseudomonas aeruginosa. Deletion leads to significant induction H(2)O(2) resistance. This effect mediated by de-repression PA2826, which lies immediately upstream encodes glutathione peroxidase. Constitutive expression alters beta-lactam resistance P. aeruginosa via PA2826-independent manner. We...
The opportunistic human pathogen Pseudomonas aeruginosa causes rapidly progressive and tissue-destructive infections, such as hospital-acquired ventilator-associated pneumonias. Innate immune responses are critical in controlling P. the mammalian lung, demonstrated by increased susceptibility of MyD88(-/-) mice to this pathogen. Experiments conducted using bone marrow chimeric that radio-resistant cells participated initiating MyD88-dependent innate aeruginosa. In study we used a novel...
Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that utilizes polar type IV pili (T4P) for twitching motility and adhesion in the environment during infection. Pilus assembly requires FimX, GGDEF/EAL domain protein binds hydrolyzes cyclic di-GMP (c-di-GMP). Bacteria lacking FimX are deficient microcolony formation. We carried out an extragenic suppressor screen PA103ΔfimX bacteria to identify additional regulators of pilus assembly. Multiple mutations were mapped PA0171,...
Chronic infections resulting from biofilm formation are difficult to eradicate with current antimicrobial agents and consequently new therapies needed. This work demonstrates that the carbon monoxide-releasing molecule CORM-2, previously shown kill planktonic bacteria, also attenuates surface-associated growth of Gram-negative pathogen Pseudomonas aeruginosa by both preventing maturation killing bacteria within established biofilm. CORM-2 treatment has an additive effect when combined...
We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association ingestion P. both vitro vivo. Since interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation aeruginosa, we hypothesized...