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Article ; Online: TNFR2

Xu, Rong / Jacques, Laura C / Khandaker, Shadia / Beentjes, Daan / Leon-Rios, Miguel / Wei, Xiaoqing / French, Neil / Neill, Daniel R / Kadioglu, Aras

Cell reports

2023 Volume 42, Issue 2, Page(s) 112054

Abstract: Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and ... ...

Abstract	Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and have upregulated TNFR2 expression. TNFR2-deficient mice have compromised Treg cell responses and highly activated IL-17A-producing γδ T cell (γδT17) responses, resulting in significantly enhanced neutrophil infiltration, tissue damage, and rapid development of bacteremia, mirroring responses in Treg cell-depleted mice. Deletion of total Treg cells predominantly activate IFNγ-T cell responses, whereas adoptive transfer of TNFR2
MeSH term(s)	Mice ; Animals ; Pneumonia, Pneumococcal/metabolism ; T-Lymphocytes, Regulatory/metabolism ; Interleukin-17/metabolism ; Receptors, Tumor Necrosis Factor, Type II ; Lung/metabolism ; Bacteremia ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell, gamma-delta/metabolism
Chemical Substances	Interleukin-17 ; Receptors, Tumor Necrosis Factor, Type II ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112054
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Helicobacter pylori CagA seropositivity in adult Bangladeshi patients with peptic ulcer and erosion

Fahmida Rahman / Khandaker Shadia / Salma Khatun / Mafruha Mahmud / Indrajit Kumar Dutta / Jalaluddin Ashraful Haq

IMC Journal of Medical Science, Vol 14, Iss 1, Pp 1-

2020 Volume 5

Abstract: Background: CagA IgG antibody in sera might indicate presence of virulent Helicobacter pylori in patients with peptic ulcer disease. Present study was performed to find out the prevalence of CagA IgG antibody in patients with peptic ulcer/erosion. ... ...

Abstract	Background: CagA IgG antibody in sera might indicate presence of virulent Helicobacter pylori in patients with peptic ulcer disease. Present study was performed to find out the prevalence of CagA IgG antibody in patients with peptic ulcer/erosion. Methods: Any case that had peptic ulcer/erosion, plus positive for rapid urease test (RUT) or H. pylori stool antigen (HpSAg) or serum anti-H. pylori IgG/IgA were included in the study and named as H. pylori positive case. H. pylori positive cases were tested for CagA IgG antibody. Anti-H. pylori IgG, IgA and CagA IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and stool antigen by rapid immunochromatographic test (ICT). Urease production in biopsy sample was detected by RUT. Results: Total 86 H. pylori positive patients were included in the study. Out of 86 patients, CagA IgG was positive in 34 (39.5%; 95% CI: 0.30,0.50) cases. CagA seropositivity rate in ulcer and erosion cases were 58.8% (95% CI: 0.36,0.78) and 34.8% (95% CI: 0.25,0.47) respectively. H. pylori stool antigen and IgA antibodies were positive in all (100%) CagA antibody positive ulcer cases while the rates were significantly less among the CagA antibody negative cases (42.8% and 28.6%; p<0.05). However, in CagA antibody positive erosion cases, the rates were not significantly different from CagA antibody negative cases. Conclusion: The study has demonstrated that the CagA positive strain is less prevalent in erosion than ulcer cases. IMC J Med Sci 2020; 14(1): 006. EPub date: 05 April 2020 *Correspondence: J. Ashraful Haq, Department of Microbiology, Ibrahim Medical College, 1/A Ibrahim Sarani, Segunbagicha, Dhaka 1000, Bangladesh. Email: jahaq54@yahoo.com 2a: present address
Keywords	Medicine ; R
Subject code	630
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Ibrahim Medical College
Document type	Article ; Online
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Article ; Online: Helicobacter pylori infection in diabetes mellitus patients with peptic ulcer disease

Salma Khatun / Khandaker Shadia / Mafruha Mahmud / Sraboni Mazumder / Indrajit Kumar Dutta / Fahmida Rahman / Md. Shariful Alam Jilani / Jalaluddin Ashraful Haq

IMC Journal of Medical Science, Vol 14, Iss 2, Pp 1-

2021 Volume 6

Abstract: Background and objectives: Helicobacter pylori infection is suspected to be associated with extra-gastrointestinal disorders such as diabetes mellitus (DM). It is still a subject of investigation whether H. pylori has a pathogenic role on DM or diabetic ... ...

Abstract	Background and objectives: Helicobacter pylori infection is suspected to be associated with extra-gastrointestinal disorders such as diabetes mellitus (DM). It is still a subject of investigation whether H. pylori has a pathogenic role on DM or diabetic patients have an increased susceptibility to H. pylori infection. The aim of the present study was to find out the rate of H. pylori infection in individuals with and without DM. Materials and methods: The study was conducted on 72 diabetic and 19 non-diabetic adult individuals with dyspeptic symptoms attending the BIRDEM General Hospital for diagnostic endoscopy. All cases were tested for H. pylori stool antigen by rapid immunochromatographic test (ICT), urease production in biopsy samples by rapid urease test (RUT), and serum anti-H. pylori IgA and anti-CagA IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Any case that had peptic ulcer/erosion and was positive for H. pylori stool antigen or rapid urease test (RUT) was defined as H. pylori positive case. Results: There was no significant (p=0.095) difference in H. pylori infection between diabetics and non-diabetics (68.1% vs 47.4%). Presence of ulcer and erosion were not significantly different among diabetics and non-diabetics. Anti-H. pylori IgA positivity rate in H. pylori positive diabetic and non-diabetic cases were 65.3% and 55.6% (p=0.575) respectively while anti-CagA IgG rate in those cases were 46.9% and 66.7% (p=0.276) respectively. Conclusion: The present study did not reveal any significant difference in H. pylori infection between individuals with and without DM having peptic ulcer/erosion. IMC J Med Sci 2020; 14(2): 006. EPub date: 17 January 2021. OPEN ACCESS *Correspondence: J. Ashraful Haq, Department of Microbiology, Ibrahim Medical College, 1/A Ibrahim Sarani, Segunbagicha, Dhaka 1000, Bangladesh. Email: jahaq54@yahoo.com
Keywords	Medicine ; R
Subject code	630
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Ibrahim Medical College
Document type	Article ; Online
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Article ; Online: Streptococcus pneumoniae Rapidly Translocate from the Nasopharynx through the Cribriform Plate to Invade the Outer Meninges.

Audshasai, Teerawit / Coles, Jonathan A / Panagiotou, Stavros / Khandaker, Shadia / Scales, Hannah E / Kjos, Morten / Baltazar, Murielle / Vignau, Julie / Brewer, James M / Kadioglu, Aras / Yang, Marie

mBio

2022 Volume 13, Issue 4, Page(s) e0102422

Abstract: The entry routes and translocation mechanisms of microorganisms or particulate materials into the central nervous system remain obscure We report here that Streptococcus pneumoniae (pneumococcus), or polystyrene microspheres of similar size, appear in ... ...

Abstract	The entry routes and translocation mechanisms of microorganisms or particulate materials into the central nervous system remain obscure We report here that Streptococcus pneumoniae (pneumococcus), or polystyrene microspheres of similar size, appear in the meninges of the dorsal cortex of mice within minutes of inhaled delivery. Recovery of viable bacteria from dissected tissue and fluorescence microscopy show that up to at least 72 h, pneumococci and microspheres were predominantly found in the outer of the two meninges: the pachymeninx. No pneumococci were found in blood or cerebrospinal fluid. Intravital imaging through the skull, aligned with flow cytometry showed recruitment and activation of LysM
MeSH term(s)	Animals ; Central Nervous System ; Ethmoid Bone ; Meninges/microbiology ; Mice ; Nasopharynx/microbiology ; Pneumococcal Infections/microbiology ; Streptococcus pneumoniae/physiology
Language	English
Publishing date	2022-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.01024-22
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Article ; Online: Author Correction: Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity.

Panagiotou, Stavros / Chaguza, Chrispin / Yahya, Reham / Audshasai, Teerawit / Baltazar, Murielle / Ressel, Lorenzo / Khandaker, Shadia / Alsahag, Mansoor / Mitchell, Tim J / Prudhomme, Marc / Kadioglu, Aras / Yang, Marie

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5099

Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-08813-w
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Article ; Online: Author Correction: Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity.

Scientific reports

2021 Volume 11, Issue 1, Page(s) 6658

Language	English
Publishing date	2021-03-17
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-86214-1
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Article ; Online: Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity.

Scientific reports

2020 Volume 10, Issue 1, Page(s) 17313

Abstract: Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive ... ...

Abstract	Streptococcus pneumoniae is a devastating global pathogen. Prevalent in sub-Saharan Africa, pneumococcal serotype 1 is atypical in that it is rarely found as a nasopharyngeal coloniser, yet is described as one of the most common causes of invasive pneumococcal disease. Clonal sequence type (ST)-306 and ST615 are representative of the two major serotype 1 lineages A and C, respectively. Here we investigated the virulence properties and haemolytic activities of these 2 clonal types using in vivo mouse models and in vitro assays. A lethal dose of ST615 administered intranasally to mice led to the rapid onset of disease symptoms and resulted in 90% mortality. In contrast, mice exposed to the same infection dose of ST306 or a pneumolysin (Ply)-deficient ST615 failed to develop any disease symptoms. Interestingly, the 2 strains did not differ in their ability to bind the immune complement or to undergo neutrophil-mediated phagocytosis. Upon comparative genomic analysis, we found higher within-ST sequence diversity in ST615 compared with ST306 and determined that ZmpA, ZmpD proteins, and IgA protease, were uniquely found in ST615. Using cell fractionation and cell contact-dependent assay, we made the unexpected finding that ST615 harbours the expression of two haemolytic variants of Ply: a cell-wall restricted fully haemolytic Ply, and a cytosolic pool of Ply void of any detectable haemolytic activity. This is the first time such a phenomenon has been described. We discuss the biological significance of our observation in relation to the aptitude of the pneumococcus for sustaining its human reservoir.
MeSH term(s)	Animals ; Bacterial Proteins ; Female ; Hemolysis ; Humans ; Mice ; Serogroup ; Streptococcus pneumoniae/classification ; Streptococcus pneumoniae/genetics ; Streptococcus pneumoniae/pathogenicity ; Streptolysins ; Virulence
Chemical Substances	Bacterial Proteins ; Streptolysins ; plY protein, Streptococcus pneumoniae
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-73454-w
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Article ; Online: Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin.

Jacques, Laura C / Panagiotou, Stavros / Baltazar, Murielle / Senghore, Madikay / Khandaker, Shadia / Xu, Rong / Bricio-Moreno, Laura / Yang, Marie / Dowson, Christopher G / Everett, Dean B / Neill, Daniel R / Kadioglu, Aras

Nature communications

2020 Volume 11, Issue 1, Page(s) 1892

Abstract: Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify ... ...

Abstract	Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.
MeSH term(s)	A549 Cells ; Animals ; Autolysis ; Bacteremia/microbiology ; Bacterial Proteins/metabolism ; Bacterial Toxins ; Cell Survival ; Disease Models, Animal ; Epithelial Cells/microbiology ; Female ; Humans ; Lung/microbiology ; Lung/pathology ; Mice ; Mice, Inbred BALB C ; Nasopharynx/microbiology ; Pneumococcal Infections/microbiology ; Pneumococcal Infections/pathology ; Serogroup ; Streptococcus pneumoniae/metabolism ; Streptococcus pneumoniae/pathogenicity ; Streptolysins/metabolism ; Virulence ; Virulence Factors
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Streptolysins ; Virulence Factors ; plY protein, Streptococcus pneumoniae
Language	English
Publishing date	2020-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-15751-6
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Article ; Online: Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.

Shears, Rebecca K / Jacques, Laura C / Naylor, Georgia / Miyashita, Lisa / Khandaker, Shadia / Lebre, Filipa / Lavelle, Ed C / Grigg, Jonathan / French, Neil / Neill, Daniel R / Kadioglu, Aras

The Journal of allergy and clinical immunology

2020 Volume 145, Issue 4, Page(s) 1272–1284.e6

Abstract: Background: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne ... ...

Abstract	Background: The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). Objectives: We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. Methods: We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. Results: We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. Conclusion: Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.
MeSH term(s)	Animals ; Bacteremia ; Carrier State ; Cells, Cultured ; Disease Models, Animal ; Disease Progression ; Disease Susceptibility ; Humans ; Lung/immunology ; Lung/microbiology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nasopharynx/microbiology ; Nasopharynx/pathology ; Particulate Matter/adverse effects ; Phagocytosis ; Pneumonia, Pneumococcal/epidemiology ; Pneumonia, Pneumococcal/immunology ; Risk ; Streptococcus pneumoniae/physiology ; Vehicle Emissions
Chemical Substances	Particulate Matter ; Vehicle Emissions
Language	English
Publishing date	2020-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2019.11.039
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Article ; Online: Activity of Mecillinam and Clavulanic Acid on ESBL Producing and Non- ESBL Producing Escherichia Coli Isolated From UTI Cases

Khandaker Shadia / Abdullah Akhtar Ahmed / Lovely Barai / Fahmida Rahman / Nusrat Tahmina / J. Ashraful Haq

IMC Journal of Medical Science, Vol 8, Iss 2, Pp 56-

2014 Volume 60

Abstract: Mecillinam is one of the very few oral antibacterial agents used against extended spectrum b-lactamase (ESBL) producing Escherichia coli (E. coli) causing urinary tract infection (UTI)). It is reported that, resistance to mecillinam can be reversed to ... ...

Abstract	Mecillinam is one of the very few oral antibacterial agents used against extended spectrum b-lactamase (ESBL) producing Escherichia coli (E. coli) causing urinary tract infection (UTI)). It is reported that, resistance to mecillinam can be reversed to some extent by adding beta lactamase inhibitor like clavulanic acid. The present study was aimed to determine in-vitro activity of mecillinam and mecillinam-clavulanic acid combination on the susceptibility of ESBL producing and non-ESBL producing E. coli. Total 124 E. coli (78 ESBL positive and 46 ESBL negative) isolates from urine samples of patients with UTI were included in the study. Organisms were isolated from patients attending BIRDEM General Hospital from July 2012 to December 2012. ESBL production was tested by double disc synergy test. Minimum inhibitory concentration (MIC) of mecillinam and clavulanic acid against E. coli was determined by agar dilution method. Of the total E. coli isolates, 62.9% was ESBL positive and 37.1% was negative for ESBL. Out of ESBL positive isolates, 75.6% was sensitive to mecillinam while ESBL negative isolates showed the sensitivity as 67.4%. The sensitivity to mecillinam of ESBL positive and negative isolates increased to 85.9% and 86.9% respectively by addition of clavulanic acid with mecillinam. The MIC values of intermediate and resistant isolates converted to sensitive MIC range after addition of clavulanic acid with mecillinam. Conversion of resistance of ESBL producing isolates by adding clavulanic acid was also evident by the reduction of MIC50 and MIC90 from 4µg/ml to £1 µg/ml and from 128 µg/ml to 64 µg/ml respectively. Similar trend of reduction of MICs was also observed in non-ESBLs. In conclusion, both ESBL positive and negative E. coli demonstrated considerable sensitivity to mecillinam and the sensitivity increased significantly (p<0.05) by adding clavulanic acid with mecillinam. Ibrahim Med. Coll. J. 2014; 8(2): 56-60
Keywords	Medicine ; R
Subject code	630
Language	English
Publishing date	2014-07-01T00:00:00Z
Publisher	Ibrahim Medical College
Document type	Article ; Online
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