STAT3 Inhibits Autocrine IFN Signaling in Type I Conventional Dendritic Cells.

Type I conventional dendritic cells (cDC1s) are an essential Ag-presenting population required for generating adaptive immunity against intracellular pathogens and tumors. While the transcriptional control of cDC1 development is well understood, the mechanisms by which extracellular stimuli regulate cDC1 function remain unclear. We previously demonstrated that the cytokine-responsive transcriptional regulator STAT3 inhibits polyinosinic:polycytidylic acid [poly(I:C)]-induced cDC1 maturation and cDC1-mediated antitumor immunity in murine breast cancer, indicating an intrinsic, suppressive role for STAT3 in cDC1s. To probe transcriptional mechanisms regulating cDC1 function, we generated novel RNA sequencing datasets representing poly(I:C)-, IL-10-, and STAT3-mediated gene expression responses in murine cDC1s. Bioinformatics analyses indicated that poly(I:C) stimulates multiple inflammatory pathways independent of STAT3, while IL-10-activated STAT3 uniquely inhibits the poly(I:C)-induced type I IFN (IFN-I) transcriptional response. We validated this mechanism using purified cDC1s deficient for STAT3 or IFN signaling. Our data reveal IL-10-activated STAT3 suppresses production of IFN-ß and IFN-γ, accrual of tyrosine phosphorylated STAT1, and IFN-stimulated gene expression in cDC1s after poly(I:C) exposure. Moreover, we found that maturation of cDC1s in response to poly(I:C) is dependent on the IFN-I receptor, but not the type II IFN receptor, or IFN-λ. Taken together, we elucidate an essential role for STAT3 in restraining autocrine IFN-I signaling in cDC1s elicited by poly(I:C) stimulation, and we provide novel RNA sequencing datasets that will aid in further delineating inflammatory and anti-inflammatory mechanisms in cDC1s.

Identification of Clinically Significant Cytokine Signature Clusters in Patients With Septic Shock.

OBJECTIVES: To identify cytokine signature clusters in patients with septic shock. DESIGN: Prospective observational cohort study. SETTING: Single academic center in the United States. PATIENTS: Adult (≥ 18 yr old) patients admitted to the medical ICU with septic shock requiring vasoactive medication support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fourteen patients with septic shock completed cytokine measurement at time of enrollment (t 1 ) and 24 hours later (t 2 ). Unsupervised random forest analysis of the change in cytokines over time, defined as delta (t 2 -t 1 ), identified three clusters with distinct cytokine profiles. Patients in cluster 1 had the lowest initial levels of circulating cytokines that decreased over time. Patients in cluster 2 and cluster 3 had higher initial levels that decreased over time in cluster 2 and increased in cluster 3. Patients in clusters 2 and 3 had higher mortality compared with cluster 1 (clusters 1-3: 11% vs 31%; odds ratio [OR], 3.56 [1.10-14.23] vs 54% OR, 9.23 [2.89-37.22]). Cluster 3 was independently associated with in-hospital mortality (hazard ratio, 5.24; p = 0.005) in multivariable analysis. There were no significant differences in initial clinical severity scoring or steroid use between the clusters. Analysis of either t 1 or t 2 cytokine measurements alone or in combination did not reveal clusters with clear clinical significance. CONCLUSIONS: Longitudinal measurement of cytokine profiles at initiation of vasoactive medications and 24 hours later revealed three distinct cytokine signature clusters that correlated with clinical outcomes.

Helmet noninvasive ventilation in acute hypoxic respiratory failure.

PURPOSE OF REVIEW: Invasive mechanical ventilation is a lifesaving intervention for patients with severe acute hypoxic respiratory failure (AHRF), but it is associated with neuromuscular, cognitive, and infectious complications. Noninvasive ventilation (NIV) may provide sufficient respiratory support without these complications. The helmet interface for NIV could address concerns raised for the use of NIV as first-line therapy in AHRF. This review will summarize and appraise the current evidence for helmet NIV in AHRF. RECENT FINDINGS: There are only six randomized controlled trials comparing helmet NIV to standard nasal cannula, facemask NIV, or high-flow nasal oxygen in patients with AHRF. Lower rates of endotracheal intubations and fewer days of mechanical ventilation were reported, with inconsistent findings on patient survival. Facemask NIV may worsen preexisting lung injury, delay intubations, and be inferior at delivering lung protective ventilation strategies compared with mechanical ventilation. The helmet interface could circumvent some of these concerns through the delivery of higher positive end expiratory pressure and more uniform distribution of negative pleural pressure. SUMMARY: There is limited evidence to support or refute the use of helmet NIV in AHRF. Further studies investigating the interface of helmet in NIV as a separate clinical entity are needed.

WITHDRAWN: Update in Critical Care 2021.

Ahead of Print article withdrawn by publisher.

Providing respiratory and ventilation care in the face of shifting evidence: current opinion in critical care.

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.

Bedside estimates of dead space using end-tidal CO2 are independently associated with mortality in ARDS.

PURPOSE: In acute respiratory distress syndrome (ARDS), dead space fraction has been independently associated with mortality. We hypothesized that early measurement of the difference between arterial and end-tidal CO2 (arterial-ET difference), a surrogate for dead space fraction, would predict mortality in mechanically ventilated patients with ARDS. METHODS: We performed two separate exploratory analyses. We first used publicly available databases from the ALTA, EDEN, and OMEGA ARDS Network trials (N = 124) as a derivation cohort to test our hypothesis. We then performed a separate retrospective analysis of patients with ARDS using University of Chicago patients (N = 302) as a validation cohort. RESULTS: The ARDS Network derivation cohort demonstrated arterial-ET difference, vasopressor requirement, age, and APACHE III to be associated with mortality by univariable analysis. By multivariable analysis, only the arterial-ET difference remained significant (P = 0.047). In a separate analysis, the modified Enghoff equation ((PaCO2-PETCO2)/PaCO2) was used in place of the arterial-ET difference and did not alter the results. The University of Chicago cohort found arterial-ET difference, age, ventilator mode, vasopressor requirement, and APACHE II to be associated with mortality in a univariate analysis. By multivariable analysis, the arterial-ET difference continued to be predictive of mortality (P = 0.031). In the validation cohort, substitution of the arterial-ET difference for the modified Enghoff equation showed similar results. CONCLUSION: Arterial to end-tidal CO2 (ETCO2) difference is an independent predictor of mortality in patients with ARDS.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

External Validation of an Acute Respiratory Distress Syndrome Prediction Model Using Radiology Reports.

OBJECTIVES: Acute respiratory distress syndrome is frequently under recognized and associated with increased mortality. Previously, we developed a model that used machine learning and natural language processing of text from radiology reports to identify acute respiratory distress syndrome. The model showed improved performance in diagnosing acute respiratory distress syndrome when compared to a rule-based method. In this study, our objective was to externally validate the natural language processing model in patients from an independent hospital setting. DESIGN: Secondary analysis of data across five prospective clinical studies. SETTING: An urban, tertiary care, academic hospital. PATIENTS: Adult patients admitted to the medical ICU and at-risk for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The natural language processing model was previously derived and internally validated in burn, trauma, and medical patients at Loyola University Medical Center. Two machine learning models were examined with the following text features from qualifying radiology reports: 1) word representations (n-grams) and 2) standardized clinical named entity mentions mapped from the National Library of Medicine Unified Medical Language System. The models were externally validated in a cohort of 235 patients at the University of Chicago Medicine, among which 110 (47%) were diagnosed with acute respiratory distress syndrome by expert annotation. During external validation, the n-gram model demonstrated good discrimination between acute respiratory distress syndrome and nonacute respiratory distress syndrome patients (C-statistic, 0.78; 95% CI, 0.72-0.84). The n-gram model had a higher discrimination for acute respiratory distress syndrome when compared with the standardized named entity model, although not statistically significant (C-statistic 0.78 vs 0.72; p = 0.09). The most important features in the model had good face validity for acute respiratory distress syndrome characteristics but differences in frequencies did occur between hospital settings. CONCLUSIONS: Our computable phenotype for acute respiratory distress syndrome had good discrimination in external validation and may be used by other health systems for case-identification. Discrepancies in feature representation are likely due to differences in characteristics of the patient cohorts.

Temperature Trajectory Subphenotypes Correlate With Immune Responses in Patients With Sepsis.

OBJECTIVES: We recently found that distinct body temperature trajectories of infected patients correlated with survival. Understanding the relationship between the temperature trajectories and the host immune response to infection could allow us to immunophenotype patients at the bedside using temperature. The objective was to identify whether temperature trajectories have consistent associations with specific cytokine responses in two distinct cohorts of infected patients. DESIGN: Prospective observational study. SETTING: Large academic medical center between 2013 and 2019. SUBJECTS: Two cohorts of infected patients: 1) patients in the ICU with septic shock and 2) hospitalized patients with Staphylococcus aureus bacteremia. INTERVENTIONS: Clinical data (including body temperature) and plasma cytokine concentrations were measured. Patients were classified into four temperature trajectory subphenotypes using their temperature measurements in the first 72 hours from the onset of infection. Log-transformed cytokine levels were standardized to the mean and compared with the subphenotypes in both cohorts. MEASUREMENTS AND MAIN RESULTS: The cohorts consisted of 120 patients with septic shock (cohort 1) and 88 patients with S. aureus bacteremia (cohort 2). Patients from both cohorts were classified into one of four previously validated temperature subphenotypes: "hyperthermic, slow resolvers" (n = 19 cohort 1; n = 13 cohort 2), "hyperthermic, fast resolvers" (n = 18 C1; n = 24 C2), "normothermic" (n = 54 C1; n = 31 C2), and "hypothermic" (n = 29 C1; n = 20 C2). Both "hyperthermic, slow resolvers" and "hyperthermic, fast resolvers" had high levels of G-CSF, CCL2, and interleukin-10 compared with the "hypothermic" group when controlling for cohort and timing of cytokine measurement (p < 0.05). In contrast to the "hyperthermic, slow resolvers," the "hyperthermic, fast resolvers" showed significant decreases in the levels of several cytokines over a 24-hour period, including interleukin-1RA, interleukin-6, interleukin-8, G-CSF, and M-CSF (p < 0.001). CONCLUSIONS: Temperature trajectory subphenotypes are associated with consistent cytokine profiles in two distinct cohorts of infected patients. These subphenotypes could play a role in the bedside identification of cytokine profiles in patients with sepsis.

Evolving targets for sedation during mechanical ventilation.

PURPOSES OF REVIEW: Critically ill patients frequently require mechanical ventilation as part of their care. Administration of analgesia and sedation to ensure patient comfort and facilitate mechanical ventilation must be balanced against the known negative consequences of excessive sedation. The present review focuses on the current evidence for sedation management during mechanical ventilation, including choice of sedatives, sedation strategies, and special considerations for acute respiratory distress syndrome (ARDS). RECENT FINDINGS: The Society of Critical Care Medicine recently published their updated clinical practice guidelines for analgesia, agitation, sedation, delirium, immobility, and sleep in adult patients in the ICU. Deep sedation, especially early in the course of mechanical ventilation, is associated with prolonged time to liberation from mechanical ventilation, longer ICU stays, longer hospital stays, and increased mortality. Dexmedetomidine may prevent ICU delirium when administered nocturnally at low doses; however, it was not shown to improve mortality when used as the primary sedative early in the course of mechanical ventilation, though the majority of patients in the informing study failed to achieve the prescribed light level of sedation. In a follow up to the ACURASYS trial, deep sedation with neuromuscular blockade did not result in improved mortality compared to light sedation in patients with severe ARDS. SUMMARY: Light sedation should be targeted early in the course of mechanical ventilation utilizing daily interruptions of sedation and/or nursing protocol-based algorithms, even in severe ARDS.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

Noninvasive approach for de novo acute hypoxemic respiratory failure: noninvasive ventilation, high-flow nasal cannula, both or none?

PURPOSE OF REVIEW: To summarize the recent evidence regarding the use of noninvasive strategies for de novo acute hypoxemic respiratory failure (AHRF). RECENT FINDINGS: New guidelines for the use of noninvasive ventilation (NIV) in acute respiratory failure have been published. In parallel, high-flow nasal cannula (HFNC) is an emerging noninvasive strategy for AHRF patients. Although some have cautioned against the use of NIV in AHRF, new encouraging data about the use of a helmet interface for NIV in acute respiratory distress syndrome may overcome the limitations of facemask NIV. SUMMARY: In the last two decades, the use of NIV and HFNC in patients with AHRF has considerably expanded, changing the paradigm of management of AHRF. Choice of each technique should be based according to centre experience and patient tolerability. However, when using noninvasive strategies for AHRF, it is crucial to predefine specific criteria for intubation and monitor patients closely for early detection of clinical deterioration to avoid delayed intubation.

Optimal Ventilator Strategies in Acute Respiratory Distress Syndrome.

Mechanical ventilation practices in patients with acute respiratory distress syndrome (ARDS) have progressed with a growing understanding of the disease pathophysiology. Paramount to the care of affected patients is the delivery of lung-protective mechanical ventilation which prioritizes tidal volume and plateau pressure limitation. Lung protection can probably be further enhanced by scaling target tidal volumes to the specific respiratory mechanics of individual patients. The best procedure for selecting optimal positive end-expiratory pressure (PEEP) in ARDS remains uncertain; several relevant issues must be considered when selecting PEEP, particularly lung recruitability. Noninvasive ventilation must be used with caution in ARDS as excessively high respiratory drive can further exacerbate lung injury; newer modes of delivery offer promising approaches in hypoxemic respiratory failure. Airway pressure release ventilation offers an alternative approach to maximize lung recruitment and oxygenation, but clinical trials have not demonstrated a survival benefit of this mode over conventional ventilation strategies. Rescue therapy with high-frequency oscillatory ventilation is an important option in refractory hypoxemia. Despite a disappointing lack of benefit (and possible harm) in patients with moderate or severe ARDS, possibly due to lung hyperdistention and right ventricular dysfunction, high-frequency oscillation may improve outcome in patients with very severe hypoxemia.

One-Year Outcomes in Patients With Acute Respiratory Distress Syndrome Enrolled in a Randomized Clinical Trial of Helmet Versus Facemask Noninvasive Ventilation.

OBJECTIVES: Many survivors of acute respiratory distress syndrome have poor long-term outcomes possibly due to supportive care practices during "invasive" mechanical ventilation. Helmet noninvasive ventilation in acute respiratory distress syndrome may reduce intubation rates; however, it is unknown if avoiding intubation with helmet noninvasive ventilation alters the consequences of surviving acute respiratory distress syndrome. DESIGN: Long-term follow-up data from a previously published randomized controlled trial. PATIENTS: Adults patients with acute respiratory distress syndrome enrolled in a previously published clinical trial. SETTING: Adult ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was functional independence at 1 year after hospital discharge defined as independence in activities of daily living and ambulation. At 1 year, patients were surveyed to assess for functional independence, survival, and number of institution-free days, defined as days alive spent living at home. The presence of ICU-acquired weakness and functional independence was also assessed by a blinded therapist on hospital discharge. On hospital discharge, there was a greater prevalence of ICU-acquired weakness (79.5% vs 38.6%; p = 0.0002) and less functional independence (15.4% vs 50%; p = 0.001) in the facemask group. One-year follow-up data were collected for 81 of 83 patients (97.6%). One-year mortality was higher in the facemask group (69.2% vs 43.2%; p = 0.017). At 1 year, patients in the helmet group were more likely to be functionally independent (40.9% vs 15.4%; p = 0.015) and had more institution-free days (median, 268.5 [0-354] vs 0 [0-323]; p = 0.017). CONCLUSIONS: Poor functional recovery after invasive mechanical ventilation for acute respiratory distress syndrome is common. Helmet noninvasive ventilation may be the first intervention that mitigates the long-term complications that plague survivors of acute respiratory distress syndrome managed with noninvasive ventilation.

Experimental platform utilising melting curve technology for detection of mutations in Mycobacterium tuberculosis isolates.

Tuberculosis (TB) remains one of the most deadly infections with approximately a quarter of cases not being identified and/or treated mainly due to a lack of resources. Rapid detection of TB or drug-resistant TB enables timely adequate treatment and is a cornerstone of effective TB management. We evaluated the analytical performance of a single-tube assay for multidrug-resistant TB (MDR-TB) on an experimental platform utilising RT-PCR and melting curve analysis that could potentially be operated as a point-of-care (PoC) test in resource-constrained settings with a high burden of TB. Firstly, we developed and evaluated the prototype MDR-TB assay using specimens extracted from well-characterised TB isolates with a variety of distinct rifampicin and isoniazid resistance conferring mutations and nontuberculous Mycobacteria (NTM) strains. Secondly, we validated the experimental platform using 98 clinical sputum samples from pulmonary TB patients collected in high MDR-TB settings. The sensitivity of the platform for TB detection in clinical specimens was 75% for smear-negative and 92.6% for smear-positive sputum samples. The sensitivity of detection for rifampicin and isoniazid resistance was 88.9 and 96.0% and specificity was 87.5 and 100%, respectively. Observed limitations in sensitivity and specificity could be resolved by adjusting the sample preparation methodology and melting curve recognition algorithm. Overall technology could be considered a promising PoC methodology especially in resource-constrained settings based on its combined accuracy, convenience, simplicity, speed, and cost characteristics.

Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells.

AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism and has attracted significant attention as a therapeutic target for treating metabolic disorders. AMPK activity is stimulated more than 100-fold by phosphorylation of threonine 172 (Thr172). Binding of AMP to the γ subunit allosterically activates the kinase. Additionally, many small molecules, e.g. 991, have been identified that bind between the kinase domain and the carbohydrate-binding module of the ß subunit, stabilising their interaction and leading to activation. It was reported recently that non-phosphorylated Thr172 AMPK is activated by AMP and A769662. We present here the crystal structure of non-phosphorylated Thr172 AMPK in complex with AMP and 991. This structure reveals that the activation loop, as well as the complex overall, is similar to the Thr172 phosphorylated complex. We find that in the presence of AMP and 991 non-phosphorylated Thr172, AMPK is much less active than the Thr172 phosphorylated enzyme. In human cells, the basal level of Thr172 phosphorylation is very low (∼1%), but is increased 10-fold by treatment with 2-deoxyglucose. In cells lacking the major Thr172 kinases, LKB1 and CaMKKß, Thr172 phosphorylation is almost completely abolished, and AMPK activity is virtually undetectable. Our data show that AMP and 991 binding to non-phosphorylated Thr172 AMPK can induce an ordered, active-like, conformation of the activation loop explaining how AMPK activity can be measured in vitro without Thr172 phosphorylation. However, in a cellular context, phosphorylation of Thr172 is critical for significant activation of AMPK.

Molecular cloning, characterization and expression of immunoglobulin D on pathogen challenge and pathogen associated molecular patterns stimulation in freshwater carp, Catla catla.

The primordial immunoglobulin class, IgD, was the first non-IgM isotype discovered in teleosts. The crucial roles of IgM and IgZ in imparting systemic and mucosal immunity, respectively, in various fish species have been widely established. However, the putative function of a unique IgD isotype during pathogenic invasions has not been well explored. The present study reports the existence of an IgD ortholog in freshwater carp, Catla catla, and further evaluates its differential expression profile in response to bacterial, parasitic and viral antigenic exposure and pathogen associated molecular patterns (PAMPs) stimulation. The IgD of C. catla (CcIgD) cDNA sequence was found to encode 226 amino acids and confirmed homology with heavy chain delta region of Cyprinidae family members. Phylogenetic analysis of CcIgD exhibited greatest similarity with Ctenopharyngodon idella. qRT-PCR analysis revealed significant upregulation (P < 0.001) of IgD gene expression in kidney with respect to other tissues at 24 hr post-Aeromonas hydrophila challenge. CcIgD gene expression in skin was enhanced following Streptococcus uberis infection and in blood following Argulus infection and inactivated rhabdoviral antigen stimulation. Further, the treatment of bacterial and viral products (PAMPs) also triggered significant (P < 0.05) increases in CcIgD mRNA expression in kidney. These findings indicate the functional importance of teleost IgD in orchestrating tissue specific neutralization of antigens on stimulation with different pathogens and PAMPs.

Disruption of the quorum sensing regulated pathogenic traits of the biofilm-forming fish pathogen Aeromonas hydrophila by tannic acid, a potent quorum quencher.

The quorum sensing (QS) phenomenon regulates a myriad of pathogenic traits in the biofilm forming fish pathogen, Aeromonas hydrophila. Blocking the QS mechanism of A. hydrophila is a novel strategy to prevent disease in fish. This study evaluated the effect of tannic acid, a QS inhibitor, on A. hydrophila-associated QS regulated phenomena. A streaking assay with Chromobacterium violaceum (CVO26) reported the presence of N-acyl homoserine lactone (AHL) in A. hydrophila, which was confirmed by HPLC and GC-MS analysis. Tannic acid-treated A. hydrophila showed a considerable reduction in violacein production, blood haemolysis activity and the pattern of swarming motility. Biofilm formation was significantly reduced (p < 0.001) (up to 95%), after tannic acid treatment for 48 h. Analysis by qRT-PCR revealed significant downregulation (p < 0.001) of AhyI and AhyR transcripts in A. hydrophila after tannic acid treatment. Co-stimulation of Catla catla with A. hydrophila and tannic acid attenuated pathogen-induced skin haemorrhages and increased the relative survival rate up to 86.6%. The study provides a mechanistic basis of tannic acid as a QS blocker and indicates its therapeutic potential against A. hydrophila-induced pathogenesis.