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Article ; Online: Novel sequence type of carbapenem-resistant Acinetobacter pittii ST1451 with enhanced virulence isolated from septicaemic neonates in India.

Roy, Subhasree / Morita, Daichi / Bhattacharya, Sushmita / Dutta, Shanta / Basu, Sulagna

The Journal of antimicrobial chemotherapy

2024 Volume 79, Issue 4, Page(s) 779–783

Abstract: Background: The clinical relevance of Acinetobacter pittii is increasing, but reports of this organism causing neonatal sepsis are rare.: Objectives: To understand the mechanisms of resistance and virulence of A. pittii isolated from neonatal blood ... ...

Abstract	Background: The clinical relevance of Acinetobacter pittii is increasing, but reports of this organism causing neonatal sepsis are rare. Objectives: To understand the mechanisms of resistance and virulence of A. pittii isolated from neonatal blood belonging to a novel sequence type. Materials and methods: Antibiotic susceptibility, MLST, WGS, phylogenomic comparison with a global collection of carbapenemase-harbouring A. pittii were done. To study the pathogenic potential of novel A. pittii, in vitro and in vivo assays were carried out. Results and discussion: Two novel multidrug-resistant A. pittii from neonatal blood belonging to a novel sequence type 1451 (ST1451) were isolated. WGS revealed that the isolates were almost similar (147 SNP distant) and harbouring two carbapenem resistance genes blaNDM-1 with upstream ISAba125 and downstream bleMBL along with blaOXA-58 with upstream ISAba3. Other resistance genes included blaADC-25, blaOXA-533, aph(3″)-Ib, aph(3')-VIa, aph(6)-Id, aac(3)-IId, mph(E), msr(E), sul2 and tet(39), different efflux pump genes and amino acid substitutions within GyrA (Ser81Leu) and ParC (Ser84Leu; Glu88Ala) were detected among the isolates. The study genomes were closely related to four strains belonging to ST119. The isolates showed biofilm production, serum resistance, growth under iron limiting condition, surface-associated motility and adherence to host cell. Isolates induced cytokine production in the host cell and showed mice mortality. Discussion and conclusions: This study is the first report of the presence of blaNDM-1 in A. pittii from India along with another carbapenemase blaOXA-58. Emergence of highly virulent, multidrug-resistant A. pittii with attributes similar to A. baumannii calls for surveillance to identify the novel strains and their pathogenic and resistance potential.
MeSH term(s)	Animals ; Mice ; Carbapenems/pharmacology ; Anti-Bacterial Agents/pharmacology ; Virulence ; Multilocus Sequence Typing ; Acinetobacter Infections/epidemiology ; Microbial Sensitivity Tests ; Bacterial Proteins/genetics ; beta-Lactamases/genetics ; beta-Lactamases/metabolism ; Acinetobacter baumannii/genetics ; Acinetobacter
Chemical Substances	Carbapenems ; Anti-Bacterial Agents ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Journal Article
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkae024
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Book ; Online: Approximate Multiagent Reinforcement Learning for On-Demand Urban Mobility Problem on a Large Map (extended version)

Garces, Daniel / Bhattacharya, Sushmita / Bertsekas, Dimitri / Gil, Stephanie

2023

Abstract: In this paper, we focus on the autonomous multiagent taxi routing problem for a large urban environment where the location and number of future ride requests are unknown a-priori, but follow an estimated empirical distribution. Recent theory has shown ... ...

Abstract	In this paper, we focus on the autonomous multiagent taxi routing problem for a large urban environment where the location and number of future ride requests are unknown a-priori, but follow an estimated empirical distribution. Recent theory has shown that if a base policy is stable then a rollout-based algorithm with such a base policy produces a near-optimal stable policy. Although, rollout-based approaches are well-suited for learning cooperative multiagent policies with considerations for future demand, applying such methods to a large urban environment can be computationally expensive. Large environments tend to have a large volume of requests, and hence require a large fleet of taxis to guarantee stability. In this paper, we aim to address the computational bottleneck of multiagent (one-at-a-time) rollout, where the computational complexity grows linearly in the number of agents. We propose an approximate one-at-a-time rollout-based two-phase algorithm that reduces the computational cost, while still achieving a stable near-optimal policy. Our approach partitions the graph into sectors based on the predicted demand and an user-defined maximum number of agents that can be planned for using the one-at-a-time rollout approach. The algorithm then applies instantaneous assignment (IA) for re-balancing taxis across sectors and a sector-wide one-at-a-time rollout algorithm that is executed in parallel for each sector. We characterize the number of taxis $m$ that is sufficient for IA base policy to be stable, and derive a necessary condition on $m$ as time goes to infinity. Our numerical results show that our approach achieves stability for an $m$ that satisfies the theoretical conditions. We also empirically demonstrate that our proposed two-phase algorithm has comparable performance to the one-at-a-time rollout over the entire map, but with significantly lower runtimes. Comment: 11 pages, 5 figures, 1 lemma, and 2 theorems
Keywords	Computer Science - Multiagent Systems ; Computer Science - Artificial Intelligence ; Computer Science - Robotics
Subject code	006
Publishing date	2023-11-02
Publishing country	us
Document type	Book ; Online
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Article ; Online: Capsaicin derived from endemic chili landraces combats Shigella pathogen: Insights on intracellular inhibition mechanism

Das, Subhasish / Priyadarshani, Nayana / Basak, Priyanka / Maitra, Priyanka / Bhattacharya, Sushmita / Bhattacharya, Satya Sundar

Microbial Pathogenesis. 2023 Aug., v. 181 p.106210-

2023

Abstract: Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as ... ...

Abstract	Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as a natural drug for pain relief, diabetic neuropathy, psoriasis, arthritis, etc. In this study, we tried to observe the influence of locality factors on the pungency and bioactive features of Capsicum annuum L. landraces. We also checked the gastro-protective ability of these chilies, especially in the cure of shigellosis. Phytometabolite characterization and estimation were done through spectrophotometric methods. Preparative and analytical HPLC techniques were employed for extracting and purifying capsaicin-enriched fractions. Shigella flexneri growth retardation was determined through the broth dilution method. Gentamicin protection assay and ELISA were done to assess the intracellular invasion and IL-1β inflammasome production by S.flexneri. The correlation analyses postulated that phenols, flavonoids, chlorophylls, β-carotene, and capsaicin synthase upregulation strongly influenced capsaicin biosynthesis in chili cultivars. Correspondingly, the inhibitory efficacy of the HPLC-purified Balijuri-derived capsaicin was more effective than the Raja-derived capsaicin in inhibiting intracellular Shigella growth. Reduced levels of pro-inflammatory cytokine (IL1β) in capsaicin-treated Shigella-infected cells probably reduced inflammation-mediated intestinal damage, limiting bacterial spread. This investigation advocates the unique potential of local chilies in curing deadly ‘shigellosis’ with mechanistic evidence. Our observation justifies the traditional healing practices of the ethnic people of NE India.
Keywords	Capsicum annuum ; Shigella flexneri ; analgesia ; arthritis ; biosynthesis ; capsaicin ; cultivars ; cytokines ; diabetic neuropathy ; flavonoids ; gentamicin ; growth retardation ; inflammasomes ; intestines ; landraces ; metabolites ; pathogenesis ; pathogens ; psoriasis ; shigellosis ; India ; Capsicum ; Pungency ; Inflammation
Language	English
Dates of publication	2023-08
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2023.106210
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Capsaicin derived from endemic chili landraces combats Shigella pathogen: Insights on intracellular inhibition mechanism.

Das, Subhasish / Priyadarshani, Nayana / Basak, Priyanka / Maitra, Priyanka / Bhattacharya, Sushmita / Bhattacharya, Satya Sundar

Microbial pathogenesis

2023 Volume 181, Page(s) 106210

Abstract	Ethnic tribals in northeast India have been growing and maintaining local chili landraces for ages. These chilies are known for their characteristic pungency and immense therapeutic properties. Capsaicin, a significant chili metabolite, is recognized as a natural drug for pain relief, diabetic neuropathy, psoriasis, arthritis, etc. In this study, we tried to observe the influence of locality factors on the pungency and bioactive features of Capsicum annuum L. landraces. We also checked the gastro-protective ability of these chilies, especially in the cure of shigellosis. Phytometabolite characterization and estimation were done through spectrophotometric methods. Preparative and analytical HPLC techniques were employed for extracting and purifying capsaicin-enriched fractions. Shigella flexneri growth retardation was determined through the broth dilution method. Gentamicin protection assay and ELISA were done to assess the intracellular invasion and IL-1β inflammasome production by S.flexneri. The correlation analyses postulated that phenols, flavonoids, chlorophylls, β-carotene, and capsaicin synthase upregulation strongly influenced capsaicin biosynthesis in chili cultivars. Correspondingly, the inhibitory efficacy of the HPLC-purified Balijuri-derived capsaicin was more effective than the Raja-derived capsaicin in inhibiting intracellular Shigella growth. Reduced levels of pro-inflammatory cytokine (IL1β) in capsaicin-treated Shigella-infected cells probably reduced inflammation-mediated intestinal damage, limiting bacterial spread. This investigation advocates the unique potential of local chilies in curing deadly 'shigellosis' with mechanistic evidence. Our observation justifies the traditional healing practices of the ethnic people of NE India.
MeSH term(s)	Humans ; Capsaicin/pharmacology ; Capsaicin/analysis ; Fruit/chemistry ; Capsicum ; Shigella ; India
Chemical Substances	Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2023.106210
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Article ; Online: Asiatic acid inhibits intracellular Shigella flexneri growth by inducing antimicrobial peptide gene expression.

Maitra, Priyanka / Basak, Priyanka / Okamoto, Keinosuke / Miyoshi, Shin-Ichi / Dutta, Shanta / Bhattacharya, Sushmita

Journal of applied microbiology

2023 Volume 134, Issue 2

Abstract: Aims: A rapid rise in resistance to conventional antibiotics for Shigella spp. has created a problem in treating shigellosis. Hence, there is an urgent need for new and non-conventional anti-bacterial agents. The aim of this study is to show how Asiatic ...

Abstract	Aims: A rapid rise in resistance to conventional antibiotics for Shigella spp. has created a problem in treating shigellosis. Hence, there is an urgent need for new and non-conventional anti-bacterial agents. The aim of this study is to show how Asiatic acid, a plant-derived compound, inhibits the intracellular growth of Shigella flexneri. Methods and results: Shigella flexneri sensitive and resistant strains were used for checking antimicrobial activity of Asiatic acid by gentamicin protection assay. Asiatic acid inhibited the intracellular growth of all strains. Gene expression analysis showed antimicrobial peptide (AMP) up-regulation by Asiatic acid in intestinal cells. Further western blot analysis showed that ERK, p38, and JNK are activated by Asiatic acid. ELISA was performed to check IL-8, IL-6, and cathelicidin secretion. The antibacterial effect of Asiatic acid was further verified in an in vivo mouse model. Conclusions: The reason behind the antibacterial activities of Asiatic acid is probably over-expression of antimicrobial peptide genes. Besides, direct antimicrobial activities, antimicrobial peptides also carry immunomodulatory activities. Here, Asiatic acid increased IL-6 and IL-8 secretion to induce inflammation. Overall, Asiatic acid up-regulates antimicrobial peptide gene expression and inhibits intracellular S. flexneri growth. Moreover, Asiatic acid reduced bacterial growth and recovered intestinal tissue damages in in vivo mice model.
MeSH term(s)	Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Dysentery, Bacillary/drug therapy ; Dysentery, Bacillary/microbiology ; Gene Expression ; Interleukin-6/genetics ; Interleukin-8/genetics ; Microbial Sensitivity Tests ; Shigella/genetics ; Shigella flexneri/genetics ; Antimicrobial Peptides/pharmacology
Chemical Substances	Anti-Bacterial Agents ; asiatic acid (9PA5A687X5) ; Interleukin-6 ; Interleukin-8 ; Antimicrobial Peptides
Language	English
Publishing date	2023-01-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1358023-1
ISSN	1365-2672 ; 1364-5072
ISSN (online)	1365-2672
ISSN	1364-5072
DOI	10.1093/jambio/lxac076
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Book ; Online: Multiagent Reinforcement Learning for Autonomous Routing and Pickup Problem with Adaptation to Variable Demand

Garces, Daniel / Bhattacharya, Sushmita / Gil, Stephanie / Bertsekas, Dimitri

2022

Abstract: We derive a learning framework to generate routing/pickup policies for a fleet of autonomous vehicles tasked with servicing stochastically appearing requests on a city map. We focus on policies that 1) give rise to coordination amongst the vehicles, ... ...

Abstract	We derive a learning framework to generate routing/pickup policies for a fleet of autonomous vehicles tasked with servicing stochastically appearing requests on a city map. We focus on policies that 1) give rise to coordination amongst the vehicles, thereby reducing wait times for servicing requests, 2) are non-myopic, and consider a-priori potential future requests, 3) can adapt to changes in the underlying demand distribution. Specifically, we are interested in policies that are adaptive to fluctuations of actual demand conditions in urban environments, such as on-peak vs. off-peak hours. We achieve this through a combination of (i) an online play algorithm that improves the performance of an offline-trained policy, and (ii) an offline approximation scheme that allows for adapting to changes in the underlying demand model. In particular, we achieve adaptivity of our learned policy to different demand distributions by quantifying a region of validity using the q-valid radius of a Wasserstein Ambiguity Set. We propose a mechanism for switching the originally trained offline approximation when the current demand is outside the original validity region. In this case, we propose to use an offline architecture, trained on a historical demand model that is closer to the current demand in terms of Wasserstein distance. We learn routing and pickup policies over real taxicab requests in San Francisco with high variability between on-peak and off-peak hours, demonstrating the ability of our method to adapt to real fluctuation in demand distributions. Our numerical results demonstrate that our method outperforms alternative rollout-based reinforcement learning schemes, as well as other classical methods from operations research. Comment: 8 pages, 6 figures, 3 tables, accepted to ICRA 2023
Keywords	Computer Science - Multiagent Systems ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning ; Computer Science - Robotics
Subject code	629
Publishing date	2022-11-27
Publishing country	us
Document type	Book ; Online
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Article ; Online: Glycyrrhizin, an inhibitor of HMGB1 induces autolysosomal degradation function and inhibits Helicobacter pylori infection.

Khan, Uzma / Karmakar, Bipul Chandra / Basak, Priyanka / Paul, Sangita / Gope, Animesh / Sarkar, Deotima / Mukhopadhyay, Asish Kumar / Dutta, Shanta / Bhattacharya, Sushmita

Molecular medicine (Cambridge, Mass.)

2023 Volume 29, Issue 1, Page(s) 51

Abstract: Background: Helicobacter pylori is a key agent for causing gastric complications linked with gastric disorders. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to ... ...

Abstract	Background: Helicobacter pylori is a key agent for causing gastric complications linked with gastric disorders. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the host's autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented during infection and gastric cancer. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. Main methods: Human gastric cancer (AGS) cells were infected with the H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression of autophagy proteins. Autophagy and lysosomal activity were monitored by fluorescence assays. A knockdown of HMGB1 was performed to verify the effect of glycyrrhizin. H. pylori infection in in vivo mice model was established and the effect of glycyrrhizin treatment was studied. Results: The autophagy-lysosomal pathway was impaired due to an increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damage in mice. Conclusion: This study showed that inhibiting HMGB1 restored lysosomal activity to ameliorate H. pylori infection. It also demonstrated the potential of glycyrrhizin as an antibacterial agent to address the problem of antimicrobial resistance.
MeSH term(s)	Humans ; Mice ; Animals ; Glycyrrhizic Acid/pharmacology ; Glycyrrhizic Acid/therapeutic use ; Glycyrrhizic Acid/metabolism ; Helicobacter pylori/metabolism ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/metabolism ; HMGB1 Protein/metabolism ; Helicobacter Infections/drug therapy ; Helicobacter Infections/metabolism ; Helicobacter Infections/microbiology ; Autophagy
Chemical Substances	Glycyrrhizic Acid (6FO62043WK) ; HMGB1 Protein
Language	English
Publishing date	2023-04-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-023-00641-6
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Article: Capsaicin Inhibits Inflammation and Gastric Damage during H pylori Infection by Targeting NF-kB–miRNA Axis

Saha, Kalyani / Sarkar, Deotima / Khan, Uzma / Karmakar, Bipul Chandra / Paul, Sangita / Mukhopadhyay, Asish K. / Dutta, Shanta / Bhattacharya, Sushmita

Pathogens. 2022 June 01, v. 11, no. 6

2022

Abstract: Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway ... ...

Abstract	Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the pro-inflammatory cytokines during infection. It also regulates the transcriptional network of several inflammatory cytokine genes. Hence, targeting NF-kB could be an important strategy to reduce pathogenesis. Moreover, treatment of H. pylori needs attention as current therapeutics lack efficacy due to antibiotic resistance, highlighting the need for alternative therapeutic approaches. In this study, we investigated the effects of capsaicin, a known NF-kB inhibitor in reducing inflammation and gastric complications during H. pylori infection. We observed that capsaicin reduced NF-kB activation and upregulation of cytokine genes in an in vivo mice model. Moreover, it affected NF-kB–miRNA interplay to repress inflammation and gastric damages. Capsaicin reduced the expression level of mir21 and mir223 along with the pro-inflammatory cytokines. The repression of miRNA further affected downstream targets such as e-cadherin and Akt. Our data represent the first evidence that treatment with capsaicin inhibits inflammation and induces antimicrobial activity during H. pylori infection. This alternative approach might open a new avenue in treating H. pylori infection, thus reducing gastric problems.
Keywords	Helicobacter pylori ; antibiotic resistance ; antimicrobial properties ; cadherins ; capsaicin ; cytokines ; inflammation ; microRNA ; pathogenesis ; therapeutics ; transcription (genetics) ; transcription factor NF-kappa B
Language	English
Dates of publication	2022-0601
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11060641
Database	NAL-Catalogue (AGRICOLA)

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Article: Capsaicin Inhibits Inflammation and Gastric Damage during

Saha, Kalyani / Sarkar, Deotima / Khan, Uzma / Karmakar, Bipul Chandra / Paul, Sangita / Mukhopadhyay, Asish K / Dutta, Shanta / Bhattacharya, Sushmita

Pathogens (Basel, Switzerland)

2022 Volume 11, Issue 6

Abstract: Helicobacter pylori (H. pylori) ...

Abstract	Helicobacter pylori (H. pylori)
Language	English
Publishing date	2022-06-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens11060641
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Article: Capsaicin Inhibits

Basak, Priyanka / Maitra, Priyanka / Khan, Uzma / Saha, Kalyani / Bhattacharya, Satya Sundar / Dutta, Moumita / Bhattacharya, Sushmita

Frontiers in pharmacology

2022 Volume 13, Page(s) 903438

Abstract: Antibiotic treatment plays an essential role in ... ...

Abstract	Antibiotic treatment plays an essential role in preventing
Language	English
Publishing date	2022-07-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.903438
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