ORCID Profile
0009-0004-2178-901X
Current Organisations
University of Newcastle Australia
,
Montpellier SupAgro
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Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JGAR.2017.11.014
Abstract: Neisseria meningitidis is an important causative agent of meningitis and/or sepsis with high morbidity and mortality. Baseline genome data on N. meningitidis, especially from developing countries such as India, are lacking. This study aimed to investigate the whole genome sequences of N. meningitidis isolates from a tertiary care centre in India. Whole-genome sequencing was performed using an Ion Torrent™ Personal Genome Machine™ (PGM) with 400-bp chemistry. Data were assembled de novo using SPAdes Genome Assembler v.5.0.0.0. Sequence annotation was performed through PATRIC, RAST and the NCBI PGAAP server. Downstream analysis of the isolates was performed using the Center for Genomic Epidemiology databases for antimicrobial resistance genes and sequence types. Virulence factors and CRISPR were analysed using the PubMLST database and CRISPRFinder, respectively. This study reports the whole genome shotgun sequences of eight N. meningitidis isolates from bloodstream infections. The genome data revealed two novel sequence types (ST12777 and ST12778), along with ST11, ST437 and ST6928. The virulence profile of the isolates matched their sequence types. All isolates were negative for plasmid-mediated resistance genes. To the best of our knowledge, this is the first report of ST11 and ST437 N. meningitidis isolates in India along with two novel sequence types (ST12777 and ST12778). These results indicate that the sequence types circulating in India are erse and require continuous monitoring. Further studies strengthening the genome data on N. meningitidis are required to understand the prevalence, spread, exact resistance and virulence mechanisms along with serotypes.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
Publisher: European Respiratory Society (ERS)
Date: 22-12-2022
DOI: 10.1183/13993003.01506-2022
Abstract: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. We assessed RIPK1 expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK′547. RIPK1 expression increased in alveolar type 1 (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients compared with never-smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T-cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS exposure, as well as airway remodelling, emphysema, and apoptotic and necroptotic cell death upon chronic CS exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-seq on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.CMET.2022.02.002
Abstract: The Krebs cycle-derived metabolite itaconate and its derivatives suppress the inflammatory response in pro-inflammatory "M1" macrophages. However, alternatively activated "M2" macrophages can take up itaconate. We therefore examined the effect of itaconate and 4-octyl itaconate (OI) on M2 macrophage activation. We demonstrate that itaconate and OI inhibit M2 polarization and metabolic remodeling. Examination of IL-4 signaling revealed inhibition of JAK1 and STAT6 phosphorylation by both itaconate and OI. JAK1 activation was also inhibited by OI in response to IL-13, interferon-β, and interferon-γ in macrophages and in T helper 2 (Th2) cells. Importantly, JAK1 was directly modified by itaconate derivatives at multiple residues, including cysteines 715, 816, 943, and 1130. Itaconate and OI also inhibited JAK1 kinase activity. Finally, OI treatment suppressed M2 macrophage polarization and JAK1 phosphorylation in vivo. We therefore identify itaconate and OI as JAK1 inhibitors, suggesting a new strategy to inhibit JAK1 in M2 macrophage-driven diseases.
Publisher: Wageningen Academic Publishers
Date: 08-07-2019
Publisher: Wiley
Date: 11-11-2021
DOI: 10.1111/CEA.13766
Abstract: Asthma is an airway inflammatory disease and a major health problem worldwide. Anti-inflammatory steroids and bronchodilators are the gold-standard therapy for asthma. However, they do not prevent the development of the disease, and critically, a subset of asthmatics are resistant to steroid therapy. To elucidate the therapeutic potential of human β-defensins (hBD), such as hBD2 mild to moderate and severe asthma. We investigated the role of hBD2 in a steroid-sensitive, house dust mite-induced allergic airways disease (AAD) model and a steroid-insensitive model combining ovalbumin-induced AAD with C muridarum (Cmu) respiratory infection. In both models, we demonstrated that therapeutic intranasal application of hBD2 significantly reduced the influx of inflammatory cells into the bronchoalveolar lavage fluid. Furthermore, key type 2 asthma-related cytokines IL-9 and IL-13, as well as additional immunomodulating cytokines, were significantly decreased after administration of hBD2 in the steroid-sensitive model. The suppression of inflammation was associated with improvements in airway physiology and treatment also suppressed airway hyper-responsiveness (AHR) in terms of airway resistance and compliance to methacholine challenge. These data indicate that hBD2 reduces the hallmark features and has potential as a new therapeutic agent in allergic and especially steroid-resistant asthma.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.MIMET.2017.07.015
Abstract: Streptococcus pneumoniae is a major cause of pneumonia, meningitis and other invasive diseases resulting in high mortality and morbidity among children under the age of five. Inaccurate identification of S. pneumoniae masks the exact estimation of disease burden and could delay treatment options. This is the common problem most frequently faced in developing countries due to several reasons that include poor infrastructure, insensitive operational procedures and lack of expertise. Inconsistent methods for phenotypic detection often delay the early identification and confirmation of S. pneumoniae. For serotyping S. pneumoniae, Quellung method is the gold standard which can be performed only on viable isolates, needs expertise and is expensive. Therefore, the data available on disease burden and serotype prevalence is not truly estimated in most of the developing countries, in turn, the use of available pneumococcal vaccines have been restricted. This current review deliberates an overview on advantages and limitations of routinely used phenotypic tests for S. pneumoniae identification. Also discussed in this review are the roles and current challenges faced by various molecular identification and serogroup/serotype identification methods of S. pneumoniae, including PCR, real time PCR, sequence analysis of different specific genes of S. pneumoniae, PCR combined with RFLP, MALDI-TOF, MLST, MLSA and WGS.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JMII.2018.03.004
Abstract: To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults. Prospective laboratory based surveillance of IPD was carried out in >18 years age group between January 2007 and July 2017, from a tertiary care hospital in South India. All Streptococcus pneumoniae culture positives from blood, CSF and sterile body fluids were characterized to identify the serotypes and AMR. A total of 408 IPD cases were characterized in this study. The overall case fatality rate in this study was 17.8% (95% confidence interval (CI): 14.1, 22.4). Pneumonia (39%), meningitis (24.3%), and septicaemia (18.4%) were the most common clinical conditions associated with IPD. Serotypes 1, 3, 5, 19F, 8, 14, 23F, 4, 19A and 6B were the predominant serotypes in this study. Penicillin non-susceptibility was low with 6.4% CONCLUSION: Serotype data from this study helped in accurate estimation of pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 protective coverage against serotypes causing IPD in India as 58.7% (95% CI: 53.8, 63.4) and 67.4% (95% CI: 62.7, 71.8) respectively. Penicillin non-susceptibility in meningeal IPD cases is 27.4%. Empirical therapy for meningeal IPD must be cephalosporin in combination with vancomycin since cefotaxime non-susceptibility in meningeal IPD is 9.9.
Publisher: Medknow
Date: 2015
Publisher: Elsevier BV
Date: 2016
Abstract: The aim of this study was to utilize the multilocus sequence typing (MLST) technique to characterise Streptococcus pneumoniae among clinical isolates in India. MLST was used to determine clonality, to establish genetic relatedness, to check for correlation between serotypes and sequence types (STs) and its relevance associated with antibiotic resistance. Forty consecutive invasive S. pneumoniae isolates in children<5 years were characterised. Preliminary identification of serotype and antibiotic susceptible profile was followed with MLST technique to identify the STs of the isolates. STs were then analysed for clonality using an eBURST algorithm and genetic relatedness using Sequence Type Analysis and Recombinational Tests version 2 software. The most common ST was ST63. Among the forty isolates, we identified nine novel STs, six of which had known alleles but in new combinations, three of which had new alleles in their sequence profile. The new STs assigned were 8501-8509. One clonal complex was found among the 40 strains characterised. The most common serotypes in this study were serotype 19F, 14 and 5. Non-susceptibility to penicillin and erythromycin was observed in 2.5% and 30% of the isolates, respectively. This study shows a significant number of novel STs among the 40 isolates characterised (9/40, 22.5%), however, internationally recognised strains were also circulating in India, indicating, there could be greater geographical variation in pneumococcal STs in India. Molecular epidemiology data is essential to understand the population dynamics of S. pneumoniae in India before the introduction of pneumococcal vaccines in NIP in India.
Publisher: MDPI AG
Date: 30-05-2018
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.MIMET.2016.09.007
Abstract: For accurate and earlier detection of invasive pneumococcal serogroup/serotypes from India, we have rearranged the African sequence of multiplex PCR provided by the Centers for Disease Control and Prevention, USA. This modified approach can successfully be adapted for earlier serotype detection of 95% of the pneumococcal strains prevalent in India.
Publisher: Wageningen Academic Publishers
Date: 08-07-2019
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 09-11-2013
Publisher: Wiley
Date: 21-03-2022
DOI: 10.1111/IMCB.12537
Abstract: Increased inflammasome responses are strongly implicated in inflammatory diseases however, their specific roles are incompletely understood. Therefore, we sought to examine the roles of nucleotide‐binding oligomerization domain–like receptor (NLR) family, pyrin domain–containing 3 (NLRP3) and absent in melanoma‐2 (AIM2) inflammasomes in cigarette smoke–induced inflammation in a model of experimental chronic obstructive pulmonary disease (COPD). We targeted NLRP3 with the inhibitor MCC950 given prophylactically or therapeutically and examined Aim2 −/− mice in cigarette smoke–induced experimental COPD. MCC950 treatment had minimal effects on disease development and/or progression. Aim2 −/− mice had increased airway neutrophils with decreased caspase‐1 levels, independent of changes in lung neutrophil chemokines. Suppressing neutrophils with anti‐Ly6G in experimental COPD in wild‐type mice reduced neutrophils in bone marrow, blood and lung. By contrast, anti‐Ly6G treatment in Aim2 −/− mice with experimental COPD had no effect on neutrophils in bone marrow, partially reduced neutrophils in the blood and had no effect on neutrophils or neutrophil caspase‐1 levels in the lungs. These findings identify that following cigarette smoke exposure, Aim2 is important for anti‐Ly6G–mediated depletion of neutrophils, suppression of neutrophil recruitment and mediates activation of caspase‐1 in neutrophils.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JIPH.2018.01.002
Abstract: Streptococcus pneumoniae is a significant cause of childhood bacterial meningitis in India. The United States Food and Drug Administration has licensed an immunochromatographic (ICT) test, Binax CSF s les from 2081 children admitted, with clinically suspected bacterial meningitis at 11 sentinel sites of hospital based sentinel surveillance network for bacterial meningitis in India between September 2009 and December 2016 were tested with ICT. Concurrent CSF cultures were processed using standard procedures. S. pneumoniae was detected thrice the number of times by ICT than by CSF culture, with a sensitivity and specificity of 100% and 95.3% respectively. This rapid ICT test proves to be of immense use as a diagnostic test for meningitis patients with/without prior antibiotic treatment, especially in facilities with limited laboratory infrastructure in resource limited settings.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2019
Publisher: Springer Science and Business Media LLC
Date: 29-01-2019
Publisher: Medknow
Date: 2015
No related grants have been discovered for Ranjith Jayaraman.