Arunava Bandyopadhaya

• Ph.D in Life Sciences ( Microbiology & Immunobiology)
• Faculty Member at Harvard University

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa ( PA ) , a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2’-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct met...

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabol...

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabol...

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabol...

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabol...

Macrophages utilize metabolic pathways to generate energy and metabolites that may be vulnerable to pathogen hijacking to favor pathogen survival and persistence. It is unclear how bacterial pathogens alter metabolic pathways in immune cells for their benefit and persistence in the infected host. We have shown that the Pseudomonas aeruginosa quorum...

Severe trauma predisposes patients to multiple independent infection episodes (MIIEs), leading to augmented morbidity and mortality. We developed a method to identify increased MIIE risk before clinical signs appear, which is fundamentally different from existing approaches entailing infections' detection after their establishment. Applying machine...

Pseudomonas aeruginosa , a bacterium that is resistant to treatment, causes serious acute, persistent, and relapsing infections in humans. There is increasing evidence that bacterial excreted small molecules play a critical role during infection. We have shown that a quorum sensing (QS)-regulated excreted small molecule, 2-AA, which is abundantly p...

Quorum sensing (QS) systems play global regulatory roles in bacterial virulence. They synchronize the expression of multiple virulence factors and they control and modulate bacterial antibiotic tolerance systems and host defense mechanisms. Therefore, it is important to obtain knowledge about QS modes of action and to test putative therapeutics tha...

Some bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volatile molecule 2-aminoacetophenone (2-AA), which has been proposed as a biomarker of Pseudomonas aeruginosa colonization in chronically infected human tissues, is critically involved in “host tole...

Human monocyte cell viability in presence of HAT inhibitor C646. MTT assay measuring viability in THP-1 cells following treatment with increasing concentrations of C646. Cells were exposed to C646 for 24 h (n = 3; means ± SDs).

Acetylation of CBP/p300 is modulated by 2-AA. Western blot analysis showing decreased CBP/p300 acetylation in 2-AA-tolerized mouse macrophage cells RAW264.7 cells following 2-AA stimulation (1 h). Data are representative of three independent experiments.

2-AA tolerization induces interaction between NF-κB p50 and HDAC1 and disrupts p65-CBP/p300 binding. (a) Co-IP assay showing increased p50/HDAC1 interaction in 2-AA-tolerized mouse macrophage RAW264.7 cells following 2-AA stimulation (1 h). (b) Co-IP assay confirming that 2-AA tolerization inhibits interaction of p65 with CBP and p300 in THP-1 cell...

Pseudomonas aeruginosa is an important nosocomial pathogen that is frequently recalcitrant to available antibiotics, underlining the urgent need for alternative therapeutic options against this pathogen. Targeting virulence functions is a promising alternative strategy as it is expected to generate less selective resistance to treatment compared to...

The mechanisms by which pathogens evade elimination without affecting host fitness are not well understood. For the pathogen Pseudomonas aeruginosa, this evasion appears to be triggered by excretion of the quorum-sensing molecule 2-aminoacetophenone, which dampens host immune responses and modulates host metabolism, thereby enabling the bacteria to...

Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial...

Cholera remains a significant health problem in developing countries due to its ability to spread rapidly and kills a high proportion of those affected. The disease is produced by Vibrio cholerae that colonizes in the human intestine and causes inflammatory diarrheal diseases. The reactogenicity of vaccine strain causes a serious problem in clinica...

Etiological agents of acute, persistent, or relapsing clinical infections are often refractory to antibiotics due to multidrug resistance and/or antibiotic tolerance. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen that causes recalcitrant and severe acute chronic and persistent human infections. Here, we target the MvfR...

Objective: To develop predictive models for early triage of burn patients based on hypersusceptibility to repeated infections. Background: Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. Methods: Secondary analysis of 459...

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tiss...

Effects of 2-AA on viability of mouse macrophages. MTT assay measuring cell viability in mouse macrophage cells after treatment with 0.2 mM, 0.4 mM or 0.8 mM 2-AA for different time points, as indicated in the figure. SDs (vertical bars) were calculated from three replicate experiments. (TIF)

Structures of 2-AA, the 2-AA metabolite 3OH-2-AA, and the 2-AA analogs 4-AA, 2NA, and MA. (TIF)

2-AA pretreated macrophages are broadly hyporesponsive to pathogen associated molecules. Macrophages were pretreated with 2-AA (0.8 mM), LPS (100 ng/ml), or PGN (100 ng/ml) for 48 h and then stimulated with LPS (1 ng/ml) or PGN (10 ng/ml) for 2 h. Activation of NF-κB (expressed as fold change over background) upon stimulation with LPS or PGN is sho...

2-AA activates NF-κB pathways and pro-inflammatory cytokines in mouse macrophages. (A) Mouse macrophages were incubated with 0.2 mM, 0.4 mM, or 2 mM 2-AA for the indicated time periods, and NF-κB activation was monitored by luciferase assays. The results are expressed as fold change compared to control cells. Mean values calculated from three repli...

2-AA modulates NF-κBp65, p38, JNK, and ERK phosphorylation in 2-AA pretreated mouse macrophages. Cells were pretreated with 2-AA (2-AA Pre) or medium only (No Pre) for 48 h and subsequently stimulated with 2 mM 2-AA for the indicated time periods. Western blotting of cellular extracts with phospho-specific antibodies was used to reveal the effects...

4-AA pretreatment does not alter activation of AP-1 in macrophages upon 4-AA stimulation. A TransAM AP-1 transcription factor assay after a 48 h pretreatment with 4-AA (0.8 mM) followed by stimulation with 4-AA, showing binding of c-Fos (A) and c-Jun (B) to the AP-1 promoter. Mean values calculated from three replicate experiments are depicted with...

Increasing evidence indicates that bacterial quorum sensing (QS) signals are important mediators of immunomodulation. However, whether microbes utilize these immunomodulatory signals to maintain infection remain unclear. Here, we show that the Pseudomonas aeruginosa QS-regulated molecule 2-amino acetophenone (2-AA) modulates host immune responses i...

Cholera remains a devastating bacterial cause of human morbidity and mortality in developing countries. The diseases is produced by a gram-negative, motile Vibrio cholerae that colonizes in the human intestine and secretes a potent cholera toxin, which ultimately stimulates cellular adenylate cyclase to cause massive intestinal fluid loss leading t...

CONTEXT: The pathogenesis of isolated hypoparathyroidism, also referred to as idiopathic hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation. OBJECTIVE: We investigated for th...

It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external env...

Vibrio cholerae activates proinflammatory response in cultured intestinal epithelial cells. In this study, we demonstrate that V. cholerae O395 infection of intestinal epithelial cells results in the activation of Akt. Inhibition of Akt significantly decreases IL-1, IL-6, and TNF- production in V. cholerae infected Int407 cells. Analysis of the mec...

Vibrio cholerae, the etiological agent of cholera, colonizes the small intestine, produces an enterotoxin and causes acute inflammatory response at intestinal epithelial surface. Chemotaxis and motility greatly influence the infectivity of V. cholerae although the role of chemotaxis genes in V. cholerae pathogenesis is less well understood. Four ch...

Vibrio cholerae, the etiological agent of cholera, leads to the induction of host cell nuclear responses and the activation of proinflammatory cytokines in the cultured intestinal epithelial cells. However, the host cell signaling pathway leading to proinflammatory response is not explored. In this study, we demonstrated that V. cholerae infection...

Vibrio cholerae, a noninvasive enteric bacterium, causing inflammatory diarrheal disease cholera, is associated with the secretion of proinflamammatory cytokines including IL-1beta in cultured epithelial cells. Incubation of Int407 with live V. cholerae resulted in increased IL-1beta mRNA expression as early as 2h of infection, reached a peak at ap...

Analyses of frequency profiles of markers on disease or drug-response related genes in diverse populations are important for the dissection of common diseases. We report the results of analyses of data on 405 SNPs from 75 such genes and a 5.2 Mb chromosome, 22 genomic region in 1871 individuals from diverse 55 endogamous Indian populations. These i...

Coordinated expression and upregulation of interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, granulocyte-macrophage colony-stimulating factor, interleukin-8, monocyte chemotactic protein-1 (MCP-1) and epithelial cell derived neutrophil activator-78, with chemoattractant and proinflammatory properties of various cyto...

Vibro cholerae, the etiological agent of cholera, colonizes the small intestine, produces an enterotoxin and causes acute inflammatory response at intestinal epithelial surface; the signals for such induction are still unknown. We determined the mRNA expression of proinflammatory and anti-inflammatory cytokines in Int407 cells following infection w...

Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning lan-guages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacoge-nomics, one needs to understand the...

Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning lan-guages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacoge-nomics, one needs to understand the...

Indian population, comprising of more than a billion people, consists of 4693 communities with several thousands of endogamous groups, 325 functioning languages and 25 scripts. To address the questions related to ethnic diversity, migrations, founder populations, predisposition to complex disorders or pharmacogenomics, one needs to understand the d...

Cholera still remains an important global predicament especially in India and other developing countries. Vibrio cholerae, the etiologic agent of cholera, colonizes the small intestine and produces an enterotoxin that is largely responsible for the watery diarrheal symptoms of the disease. Using RNA arbitrarily primed PCR, ND5 a mitochondria encode...