The adenylate cyclase toxin (ACT) of Bordetella pertussis intoxicates target cells by generating supraphysiologic levels intracellular cyclic AMP (cAMP). Since ACT kills macrophages rapidly and potently, we asked whether would also kill neutrophils. In fact, prolongs the neutrophil life span inhibiting constitutive apoptosis preventing induced exposure to live B. pertussis. Imaging pertussis-exposed neutrophils revealed that lacking induces formation extracellular traps (NETs), whereas...

ABSTRACT Whooping cough results from infection of the respiratory tract with Bordetella pertussis , and secreted adenylate cyclase toxin (ACT) is essential for bacterium to establish infection. Despite extensive study mechanism ACT cytotoxicity its effects over a range concentrations in vitro has not been observed or quantified vivo thus concentration at site unknown. The recently developed baboon model mimics prolonged transmissibility pertussis, we hypothesized that measurement...

Abstract CR3 (CD11b/CD18; αmβ2 integrin) is a conserved phagocytic receptor. The active conformation of binds the iC3b fragment complement C3 as well many host and microbial ligands, leading to actin-dependent phagocytosis. There are conflicting reports about how engagement affects fate phagocytosed substrates. Using imaging flow cytometry, we confirmed that binding internalization iC3b-opsonized polystyrene beads by primary human neutrophils was CR3-dependent. did not stimulate neutrophil...

The catalytic domain of Bordetella pertussis adenylate cyclase toxin (ACT) translocates directly across the plasma membrane mammalian cells to induce toxicity by production cAMP. Here, we use electrophysiology examine translocation into polarized epithelial that model mucosal surfaces host. We find both T84 cell monolayers and human airway cultures respond nanomolar concentrations ACT when applied basolateral membranes, with little or no response apically. induction is rapid fully explained...

Bordetella pertussis adenylate cyclase toxin (ACT) intoxicates cells by producing intracellular cAMP. B. outer membrane vesicles (OMV) contain ACT on their surface (OMV–ACT), but the properties of OMV–ACT were previously unknown. We found that in lung from a fatal case contains OMV, suggesting an involvement pathogenesis. and intoxicate with without toxin's receptor CD11b/CD18. Intoxication is blocked antitoxin anti‐CD11b antibodies, not cytochalasin‐D; contrast, unaffected either antibody...

Nucleic acid microarray (NAM) testing for detection of Staphylococcus aureus bacteremia (SAB) and S. resistance gene determinants can reduce time to targeted antibiotic administration. Evidence-based management SAB includes bedside infectious diseases (ID) consultation. As a healthcare improvement initiative at our institution, with the goal improving outcomes subjects SAB, we implemented NAM process responding positive results by directly triggered, mandatory ID...

Caveolins are membrane proteins that the major coat of caveolae, specialized lipid rafts in plasma serve as scaffolding sites for many signaling complexes. Among molecules associated with caveolins Src tyrosine kinases, whose activation regulates numerous cellular functions including balance between cell survival and death. Several mutations muscle-specific caveolin, caveolin-3, lead to a form autosomal dominant muscular dystrophy referred limb girdle type 1C (LGMD-1C). One these (here...

Bordetella pertussis, the causative agent of whooping cough, secretes and releases adenylate cyclase toxin (ACT), which is a protein bacterial that targets host cells disarms immune defenses. ACT binds filamentous haemagglutinin (FHA), surface-displayed adhesin, until now, consequences this interaction were unknown. A B. bronchiseptica mutant lacking produced more biofilm than parental strain; leading Irie et al. to propose ACT-FHA could be responsible for inhibition. Here we characterize...

Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy ceftaroline as initial therapy. We present an assessment outcomes patients initiated on early MRSA-B. This was a single-center, retrospective study adult admitted MRSA-B between July 1, 2017 and April 31, 2023. During this period, there change in...

Ciliary neurotrophic factor (CNTF)-dependent induction of expression the neuropeptide vasoactive intestinal peptide (VIP) gene is mediated by a 180-base pair cytokine response element (CyRE) in VIP promoter. To elucidate molecular mechanisms mediating transcriptional activation CNTF, intracellular signaling to CyRE has been studied neuroblastoma cell line. It shown previously that CNTF induces Stat proteins bind site within CyRE. also second protein C/EBP-like In this report, we show...

In vitro growth conditions for bacteria do not fully recapitulate the host environment. RNA sequencing transcriptome analysis allows characterization of infection gene expression profiles pathogens in complex environments. Isolation pathogen from infected tissues is critical because large amounts present crude lysates organs. A filtration method was developed that enabled enrichment RNA-seq analysis. The resulting data describe “infection transcriptome” B. pertussis murine lung. This...

Our study describes the first in vivo transposon sequencing (Tn-seq) analysis of B. pertussis and identifies genes predicted to be essential for growth a murine model intranasal infection, generating key resources future investigations into pathogenesis vaccine design.

ABSTRACT The adenylate cyclase toxin (ACT) of Bordetella pertussis does not require a receptor to generate intracellular cyclic AMP (cAMP) in broad range cell types. To intoxicate cells, ACT binds the surface, translocates its catalytic domain across membrane, and converts ATP cAMP. In cells that express integrin CD11b/CD18 (CR3), is more potent than CR3-negative cells. We find, however, maximum levels cAMP accumulation inside CR3-positive -negative are comparable. better understand how CR3...

Abstract Quality is central to value-based care, and measurement essential for assessing performance understanding improvement over time. Both care methods quality are evolving. Infectious diseases (ID) has been less engaged than other specialties in measure development, ID providers must seize the opportunity engage with development research. Antimicrobial stewardship programs an ideal starting point ID-related development; antimicrobial program interventions best practices specific,...

Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis, and antibodies to ACT protect against B. pertussis infection in mice. The therefore a strong candidate antigen for addition future acellular vaccines. In order characterize the functionality immunologic response after infection, we developed assay testing ability serum samples from subjects infected with neutralize ACT-induced cytotoxicity J774 macrophage cells. Baboons develop neutralizing anti-ACT...

The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, determine the value care provided by physicians promote improvement. Few ID-specific have been developed; herein, we provide an overview importance measurement ID, discuss issues in specific describe standards which candidate...

Our results suggest that FFR fit during CPR is poor and EMHRs provide superior fit, confirming previous research. 5 We chose to evaluate because it highly aerosolizing, physically strenuous, has been associated with occupational transmission.Strengths of our study include real-world design prospective data collection.Limitations the lack blinding or randomization use participant-reported detection.The EMHR more effective at preventing aerosol inhalation strenuous clinical work should be...

Non-immunoglobulin E (IgE)-mediated hypersensitivity reactions (HSRs) to nafcillin are commonly reported, but scarce data available guide appropriate antibiotic change following these reactions. Although cefazolin is an attractive therapeutic alternative in methicillin-susceptible Staphylococcus aureus (MSSA) infections when patients experience HSR nafcillin, more needed evaluate the tolerability of after switching from nafcillin. The purpose this study was describe who develop a suspected...

Abstract Background A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous effusion (TPE) with notable negative predictive value. Case presentation We report case patient ADA who was found have culture-positive and biopsy-proven Mycobacterium tuberculosis. Conclusions This shows importance pursuing gold standard diagnostic studies when clinical suspicion remains high despite preliminary testing. further describe gaps research improve...