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Article ; Online: Bacteria can compensate the fitness costs of amplified resistance genes via a bypass mechanism.

Pal, Ankita / Andersson, Dan I

2024 Volume 15, Issue 1, Page(s) 2333

Abstract: Antibiotic heteroresistance is a phenotype in which a susceptible bacterial population includes a small subpopulation of cells that are more resistant than the main population. Such resistance can arise by tandem amplification of DNA regions containing ... ...

Abstract	Antibiotic heteroresistance is a phenotype in which a susceptible bacterial population includes a small subpopulation of cells that are more resistant than the main population. Such resistance can arise by tandem amplification of DNA regions containing resistance genes that in single copy are not sufficient to confer resistance. However, tandem amplifications often carry fitness costs, manifested as reduced growth rates. Here, we investigated if and how these fitness costs can be genetically ameliorated. We evolved four clinical isolates of three bacterial species that show heteroresistance to tobramycin, gentamicin and tetracyclines at increasing antibiotic concentrations above the minimal inhibitory concentration (MIC) of the main susceptible population. This led to a rapid enrichment of resistant cells with up to an 80-fold increase in the resistance gene copy number, an increased MIC, and severely reduced growth rates. When further evolved in the presence of antibiotic, these strains acquired compensatory resistance mutations and showed a reduction in copy number while maintaining high-level resistance. A deterministic model indicated that the loss of amplified units was driven mainly by their fitness costs and that the compensatory mutations did not affect the loss rate of the gene amplifications. Our findings suggest that heteroresistance mediated by copy number changes can facilitate and precede the evolution towards stable resistance.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Tobramycin ; Bacteria/genetics ; Gene Amplification ; Gentamicins ; Microbial Sensitivity Tests ; Drug Resistance, Bacterial/genetics
Chemical Substances	Anti-Bacterial Agents ; Tobramycin (VZ8RRZ51VK) ; Gentamicins
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46571-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Assessment of quality of life in thyroid cancer patients using the EORTC thyroid-specific questionnaire: a prospective cross-sectional study.

Thiagarajan, Shivakumar / Fatehi, Khuzema / Menon, Nandini / Sawant, Mahesh / Pal, Ankita

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

2024 Volume 281, Issue 4, Page(s) 1953–1960

Abstract: Background: Many studies on the quality of life (QoL) among the thyroid cancer survivors have shown conflicting results. This may be since many of these studies have not used thyroid cancer-specific questionnaires.: Patients and methods: In our study ...

Abstract	Background: Many studies on the quality of life (QoL) among the thyroid cancer survivors have shown conflicting results. This may be since many of these studies have not used thyroid cancer-specific questionnaires. Patients and methods: In our study we have translated the EORTC THY-34, validated and served it in a cross-sectional study to the assess the QoL among thyroid cancer patients free of disease during their routine follow-up. Patients were categorized based on the duration from treatment completion, ATA risk stratification, treatment received, number of RAI sessions and thyroid function status during analysis. Results: Overall, 220 thyroid cancer survivors were included in this study. In general, in the EORTC QLQ-C30, the global QoL of thyroid cancer patients were good with a mean score of 72.99. The highest score was that for social functioning (89.55). In the EORTC-THY34 all the patients in the cohort had relatively lower scores (on symptom scales). Overall, there was no difference in the QLQ-C30 and THY-34 QoL with respect to any of the categorization mentioned above. However, our thyroid cancer patients QoL scores were better and/or comparable to those in published literature and they were also better or comparable to the QoL of the general population those were available in literature. Conclusions: There was no difference in the QoL scores based on various categories. To better understand the quality of life of these patients a prospective longitudinal study with baseline values and values at regular intervals might give us a better insight.
MeSH term(s)	Humans ; Quality of Life ; Cross-Sectional Studies ; Longitudinal Studies ; Prospective Studies ; Surveys and Questionnaires ; Thyroid Neoplasms/therapy
Language	English
Publishing date	2024-02-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-024-08471-w
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Article ; Online: A Systems Biology Approach To Disentangle the Direct and Indirect Effects of Global Transcription Factors on Gene Expression in Escherichia coli.

Iyer, Mahesh S / Pal, Ankita / Venkatesh, K V

Microbiology spectrum

2023 , Page(s) e0210122

Abstract: Delineating the pleiotropic effects of global transcriptional factors (TFs) is critical for understanding the system-wide regulatory response in a particular environment. Currently, with the availability of genome-wide TF binding and gene expression data ...

Abstract	Delineating the pleiotropic effects of global transcriptional factors (TFs) is critical for understanding the system-wide regulatory response in a particular environment. Currently, with the availability of genome-wide TF binding and gene expression data for Escherichia coli, several gene targets can be assigned to the global TFs, albeit inconsistently. Here, using a systematic integrated approach with emphasis on metabolism, we characterized and quantified the direct effects as well as the growth rate-mediated indirect effects of global TFs using deletion mutants of FNR, ArcA, and IHF regulators (focal TFs) under glucose fermentative conditions. This categorization enabled us to disentangle the dense connections seen within the transcriptional regulatory network (TRN) and determine the exact nature of focal TF-driven epistatic interactions with other global and pathway-specific local regulators (iTFs). We extended our analysis to combinatorial deletions of these focal TFs to determine their cross talk effects as well as conserved patterns of regulatory interactions. Moreover, we predicted with high confidence several novel metabolite-iTF interactions using inferred iTF activity changes arising from the allosteric effects of the intracellular metabolites perturbed as a result of the absence of focal TFs. Further, using compendium level computational analyses, we revealed not only the coexpressed genes regulated by these focal TFs but also the coordination of the direct and indirect target expression in the context of the economy of intracellular metabolites. Overall, this study leverages the fundamentals of TF-driven regulation, which could serve as a better template for deciphering mechanisms underlying complex phenotypes.
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02101-22
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Article: Expression of Gata Binding Protein 3 as a Prognostic Factor in Urogenital Lesions and Its Association With Morphology.

Govardhan, T / Mohapatra, Debahuti / Naik, Sujata / Das, Prateek / Mohanty, Pranita / Pal, Ankita

Cureus

2023 Volume 15, Issue 11, Page(s) e49635

Abstract: Background: Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping histopathological features. GATA binding protein 3 (GATA3), a transcription ... ...

Abstract	Background: Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping histopathological features. GATA binding protein 3 (GATA3), a transcription factor associated with urothelial tissue, has shown promise as a potential diagnostic marker. This study aimed to investigate the incidence of these malignancies, explore GATA3's involvement in urothelial cancer (UC), and determine its role in distinguishing urogenital malignancies. Materials and methods: A cross-sectional, retro-prospective, hospital-based study was conducted from May 2019 to April 2021. The surgical samples of patients who underwent transurethral resection of bladder tumour (TURBT), transurethral resection of the prostate (TURP), radical cystoprostatectomy, total and partial radical nephrectomy specimens during the study period were reviewed. Patients diagnosed with urinary bladder neoplasm and high-grade prostate neoplasm along with chromophobe, oncocytic, sarcomatoid variant and clear cell carcinoma, renal cell carcinoma were included. Immunohistochemical analysis of GATA3 expression was performed, with scoring based on nuclear staining intensity and percentage of tumor cells labeled. Results: The study included 64 patients, predominantly males over 60 years. Personal habits revealed a high prevalence of smoking (85.9%). The most prevalent symptom was hematuria (75.0%), followed by hematuria with urgency (20.3%). The most common site of lesion was posterolateral (31.3%). Urothelial cancer was the most common malignancy, primarily high-grade. Strong positive GATA3 expression was significantly associated with high-grade UC (p=0.01) and invasion (p=0.01). However, low-grade UC and papillary urothelial neoplasm of low malignant potential exhibited moderate GATA3 expression. GATA3 demonstrated potential for distinguishing UC from other histological types. Conclusion: GATA3 expression correlates with high-grade urothelial cancer and invasive behavior, suggesting its utility as a diagnostic marker in challenging cases.
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.49635
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Article: Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications.

Dharavath, Bhasker / Butle, Ashwin / Chaudhary, Akshita / Pal, Ankita / Desai, Sanket / Chowdhury, Aniket / Thorat, Rahul / Upadhyay, Pawan / Nair, Sudhir / Dutt, Amit

NPJ precision oncology

2024 Volume 8, Issue 1, Page(s) 63

Abstract: Head and neck cancer is a major cause of morbidity and mortality worldwide. The identification of genetic alterations in head and neck cancer may improve diagnosis and treatment outcomes. In this study, we report the identification and functional ... ...

Abstract	Head and neck cancer is a major cause of morbidity and mortality worldwide. The identification of genetic alterations in head and neck cancer may improve diagnosis and treatment outcomes. In this study, we report the identification and functional characterization of UBE3C-LRP5 translocation in head and neck cancer. Our whole transcriptome sequencing and RT-PCR analysis of 151 head and neck cancer tumor samples identified the LRP5-UBE3C and UBE3C-LRP5 fusion transcripts in 5.3% of patients of Indian origin (n = 151), and UBE3C-LRP5 fusion transcripts in 1.2% of TCGA-HNSC patients (n = 502). Further, whole genome sequencing identified the breakpoint of UBE3C-LRP5 translocation. We demonstrate that UBE3C-LRP5 fusion is activating in vitro and in vivo, and promotes the proliferation, migration, and invasion of head and neck cancer cells. In contrast, depletion of UBE3C-LRP5 fusion suppresses the clonogenic, migratory, and invasive potential of the cells. The UBE3C-LRP5 fusion activates the Wnt/β-catenin signaling by promoting nuclear accumulation of β-catenin, leading to upregulation of Wnt/β-catenin target genes, MYC, CCND1, TCF4, and LEF1. Consistently, treatment with the FDA-approved drug, pyrvinium pamoate, significantly reduced the transforming ability of cells expressing the fusion protein and improved survival in mice bearing tumors of fusion-overexpressing cells. Interestingly, fusion-expressing cells upon knockdown of CTNNB1, or LEF1 show reduced proliferation, clonogenic abilities, and reduced sensitivity to pyrvinium pamoate. Overall, our study suggests that the UBE3C-LRP5 fusion is a promising therapeutic target for head and neck cancer and that pyrvinium pamoate may be a potential drug candidate for treating head and neck cancer harboring this translocation.
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ISSN	2397-768X
ISSN	2397-768X
DOI	10.1038/s41698-024-00555-4
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Article ; Online: Structural and functional insights into colicin: a new paradigm in drug discovery

Calcuttawala, Fatema / Pal, Ankita / Nath, Papri / Kar, Riya / Hazra, Debraj / Pāla, Rajata

Arch Microbiol. 2022 Jan., v. 204, no. 1 p.37-37

2022

Abstract: Colicins are agents of allelopathic interactions produced by certain enterobacteria which give them a competitive advantage in the environment. These protein molecules are mostly encoded by plasmids. The colicin operon consists of the activity, immunity ... ...

Abstract	Colicins are agents of allelopathic interactions produced by certain enterobacteria which give them a competitive advantage in the environment. These protein molecules are mostly encoded by plasmids. The colicin operon consists of the activity, immunity and the lysis genes. The activity protein is responsible for the killing activity, the immunity protein protects the producer cell from the lethal action of colicin and the lysis protein facilitates its release. Colicins are primarily composed of three domains, namely the receptor-binding domain, the translocation domain and the cytotoxic domain. The protein molecule binds to its cognate receptor on the target cell via the receptor-binding domain and undergoes translocation into the cell either via the Tol system or the Ton system. After gaining entry into the target cell, there are various mechanisms by which colicins exert their lethality. These comprise DNase activity, RNase activity and pore formation in the target cell membrane or peptidoglycan synthesis inhibition. This review gives a detailed insight into the structural and functional aspect of colicins and their mode of action. This knowledge is of immense significance because colicins are being considered as very useful alternatives to conventional antibiotics in the treatment of multidrug-resistant infections. Besides, they also have a negligible harmful impact on the commensals. Thus, before tapping their therapeutic potential, it is imperative to know their structure and mechanism of action in detail.
Keywords	cell membranes ; colicins ; cytotoxicity ; death ; deoxyribonucleases ; drugs ; immunity ; mechanism of action ; multiple drug resistance ; operon ; peptidoglycans ; plasmids ; ribonucleases ; therapeutics
Language	English
Dates of publication	2022-01
Size	p. 37.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
Note	Review
ZDB-ID	124824-8
ISSN	1432-072X ; 0302-8933
ISSN (online)	1432-072X
ISSN	0302-8933
DOI	10.1007/s00203-021-02689-6
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Surface Treatment and Implant Bone Interface: A Systematic Literature Review.

Chopra, Megha / Vermani, Mayank / Swarup, Neeti / Pal, Ankita / Chowdhary, Zoya

Journal of long-term effects of medical implants

2021 Volume 30, Issue 4, Page(s) 283–294

Abstract: In the present scenario, dental implants have proven to be a very reliable and popular treatment option for partial and completely edentulous arches. The biological, chemical, local, clinician, and implant related factors determine sequence of bone ... ...

Abstract	In the present scenario, dental implants have proven to be a very reliable and popular treatment option for partial and completely edentulous arches. The biological, chemical, local, clinician, and implant related factors determine sequence of bone turnover that eventually enhances the success of implant therapy. The positioning of implant is followed by an inflammatory process that results in de novo bone formation and deposition on the implant surface. Pure titanium is commercially the prime material of choice for an implant. The implant surface can be chemically altered by a change in manufacturing, finishing, thermal treatment, blasting etching, coatings, and even sterilization procedures. These techniques have led to major innovations in implant dentistry as they roughen the surface, promoting bone deposition and stability. The current paper gives a comprehensive review of the diverse topographical characteristics of an implant surface and the altered techniques offered to create appropriate roughness to enhance osseointegration starting from fundamental to the latest techniques.
MeSH term(s)	Bone Remodeling ; Dental Implants ; Humans ; Osseointegration ; Prostheses and Implants ; Surface Properties ; Titanium
Chemical Substances	Dental Implants ; Titanium (D1JT611TNE)
Language	English
Publishing date	2021-01-18
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	1073166-0
ISSN	1940-4379 ; 1050-6934
ISSN (online)	1940-4379
ISSN	1050-6934
DOI	10.1615/JLongTermEffMedImplants.2020036820
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Article ; Online: Global pleiotropic effects in adaptively evolved

Pal, Ankita / Iyer, Mahesh S / Srinivasan, Sumana / Narain Seshasayee, Aswin Sai / Venkatesh, K V

Open biology

2022 Volume 12, Issue 2, Page(s) 210206

Abstract: Evolution facilitates emergence of fitter phenotypes by efficient allocation of cellular resources in conjunction with beneficial mutations. However, system-wide pleiotropic effects that redress the perturbations to the apex node of the transcriptional ... ...

Abstract	Evolution facilitates emergence of fitter phenotypes by efficient allocation of cellular resources in conjunction with beneficial mutations. However, system-wide pleiotropic effects that redress the perturbations to the apex node of the transcriptional regulatory networks remain unclear. Here, we elucidate that absence of global transcriptional regulator CRP in
MeSH term(s)	Biological Evolution ; Cyclic AMP Receptor Protein/genetics ; Cyclic AMP Receptor Protein/metabolism ; Energy Metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Gene Expression Regulation, Bacterial ; Metabolic Networks and Pathways ; Mutation
Chemical Substances	Cyclic AMP Receptor Protein ; Escherichia coli Proteins ; crp protein, E coli
Language	English
Publishing date	2022-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.210206
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Article ; Online: Correction to 'Global pleiotropic effects in adaptively evolved

Pal, Ankita / Iyer, Mahesh S / Srinivasan, Sumana / Narain Seshasayee, Aswin Sai / Venkatesh, K V

Open biology

2022 Volume 12, Issue 4, Page(s) 220087

Language	English
Publishing date	2022-04-06
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.220087
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Article: Global Transcriptional Regulators Fine-Tune the Translational and Metabolic Efficiency for Optimal Growth of Escherichia coli.

Iyer, Mahesh S / Pal, Ankita / Srinivasan, Sumana / Somvanshi, Pramod R / Venkatesh, K V

mSystems

2021 Volume 6, Issue 2

Abstract: Global transcriptional regulators coordinate complex genetic interactions that bestow better adaptability for an organism against external and internal perturbations. These transcriptional regulators are known to control an enormous array of genes with ... ...

Abstract	Global transcriptional regulators coordinate complex genetic interactions that bestow better adaptability for an organism against external and internal perturbations. These transcriptional regulators are known to control an enormous array of genes with diverse functionalities. However, regulator-driven molecular mechanisms that underpin precisely tuned translational and metabolic processes conducive for rapid exponential growth remain obscure. Here, we comprehensively reveal the fundamental role of global transcriptional regulators FNR, ArcA, and IHF in sustaining translational and metabolic efficiency under glucose fermentative conditions in
Language	English
Publishing date	2021-03-30
Publishing country	United States
Document type	Journal Article
ISSN	2379-5077
ISSN	2379-5077
DOI	10.1128/mSystems.00001-21
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