- Salmonella and Campylobacter epidemiology
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Vibrio bacteria research studies
- Immune Response and Inflammation
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- Research on Leishmaniasis Studies
- Aquaculture disease management and microbiota
- T-cell and B-cell Immunology
- Hepatitis Viruses Studies and Epidemiology
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Streptococcal Infections and Treatments
- Bacterial Identification and Susceptibility Testing
- Vaccine Coverage and Hesitancy
- Infective Endocarditis Diagnosis and Management
- Trypanosoma species research and implications
- Toxoplasma gondii Research Studies
- Bacterial Genetics and Biotechnology
- Gut microbiota and health
- Antibiotic Resistance in Bacteria
University of Cambridge
2015-2024
Google (United States)
2016
Wellcome Sanger Institute
2014-2015
Korea Advertising Society
2010
Kaneka (United States)
2010
Bridge University
2008
Cambridge Science Centre
2006
Imperial College London
1997-2004
Cambridge School
2004
Biology of Infection
2003
A type III protein secretion system encoded by Salmonella pathogenicity island 2 (SPI2) has been found to be required for virulence and survival within macrophages. Here, SPI2 was shown allow typhimurium avoid NADPH oxidase–dependent killing The ability of SPI2-mutant bacteria survive in macrophages cause lethal infection mice restored abrogation the respiratory burst. Ultrastructural immunofluorescence microscopy demonstrated efficient localization oxidase proximity vacuoles containing but...
The contribution of the NADPH phagocyte oxidase (phox) and inducible nitric oxide (NO) synthase (iNOS) to antimicrobial activity macrophages for Salmonella typhimurium was studied by using peritoneal phagocytes from C57BL/6, congenic gp91phox(-/)-, iNOS(-/)-, doubly immunodeficient phox(-/)-iNOS(-/)- mice. respiratory burst NO radical (NO.) made distinct contributions anti-Salmonella macrophages. oxidase-dependent killing is confined first few hours after phagocytosis, whereas iNOS...
Summary The intracellular bacterium Listeria monocytogenes can invade several types of normally non‐phagocytic cells. Entry into cultured epithelial cells requires the expression inIA , first gene an operon, comprising two genes: which encodes internalin, 800‐amino‐acid protein, and inIB a 630‐amino‐acid protein. Several genes homologous to are detected in genome L. monocytogenes; InIB is one them. We have assessed role In invasiveness by constructing isogenic chromosomal deletion mutants...
The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated gp91phox−/−, iNOS−/−, congenic wild-type mice. Although both gp91phox−/− iNOS−/− mice demonstrated increased susceptibility infection with S. compared mice, kinetics bacterial replication dramatically different mouse strains. Greater numbers present spleens livers C57BL/6 controls as early day 1 infection, all succumbed within 5 d....
Clostridium difficile persists in hospitals by exploiting an infection cycle that is dependent on humans shedding highly resistant and infectious spores. Here we show human virulent C. can asymptomatically colonize the intestines of immunocompetent mice, establishing a carrier state for many months. mice consistently shed low levels spores but, surprisingly, do not transmit to cohabiting mice. However, antibiotic treatment carriers triggers contagious supershedder state, characterized...
Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single population. They are also currently poorly understood. Here, we report on the application sophisticated experimental approaches to map spatiotemporal population dynamics bacteria during an infection. We analyzed heterogeneous traits simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic strains [WITS]) in wild-type gene-targeted...
Poultry meat and eggs contaminated with Salmonella enterica serovar Enteritidis or Typhimurium are common sources of acute gastroenteritis in humans. However, the exact nature immune mechanisms protective against infection chickens has not been characterized at molecular level. In present study, bacterial colonization, development pathological lesions, proinflammatory cytokine chemokine gene expression were investigated liver, spleen, jejunum, ileum, cecal tonsils newly hatched 6, 12, 24, 48...
ABSTRACT Infection of poultry with Salmonella enterica serovar Typhimurium poses a significant risk to public health through contamination meat from infected animals. Vaccination has been proposed control infections in chickens. However, the vaccines are currently largely empirical, and our understanding mechanisms that underpin immune clearance protection avian salmonellosis is not complete. In this study we describe cytokine, chemokine, antibody responses cellular changes primary secondary...
The mechanisms of immunity to salmonellae conferred by immunization with live vaccines were studied adoptive transfer using the mouse-virulent strain Salmonella typhimurium C5 and innately susceptible BALB/c (ltys) mice. This organism cannot establish a sublethal infection in naive Animals immunized 2 3 months earlier S. SL3261 aroA vaccine used as donors serum, spleen cells, mesenteric lymph node cells for recipients which challenged orally virulent strain. Simultaneous both immune serum...
ABSTRACT Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells recombinant gamma interferon (rIFN-γ) enhanced IL-18 production. treated in vivo anti-IL-18 antibodies showed impaired resistance to infection, increased bacterial loads liver spleen. Administration rIL-18 could protect challenge a lethal dose virulent salmonellae, dramatic reduction numbers...
Salmonella enterica sv. typhimurium (S. Typhimurium) has two metal-transporting P1-type ATPases whose actions largely overlap with respect to growth in elevated copper. Mutants lacking both over-accumulate copper relative wild-type or either single mutant. Such duplication of is unusual bacterial tolerance. Both are under the control MerR family metal-responsive transcriptional activators. Analyses periplasmic complexes identified copper-CueP as one predominant metal pools. Expression cueP...
Protective Th1 responses to Salmonella enterica do not develop in the absence of B cells. Using chimeric mice, we dissect early (innate) and late (cognate) contributions cells Th programming. cell-intrinsic MyD88 signaling is required for primary effector development, whereas Ag-specific BCR-mediated Ag presentation necessary development memory populations. Programming T cell response BCR/B MHC II independent, but requires MyD88-dependent secretion cytokines by Chimeras which lack IFN-gamma...
Significance Bacteria, such as nontyphoidal Salmonella , are responsible for a large global burden of disease. Due to limited need in developed countries and consequent lack commercial incentive, vaccines unavailable against many bacteria. Glycoconjugates constitute the standard bacterial vaccine approach, but can be costly, particularly where multivalent preparations required. This report compares low-cost vesicle-based technology, known Generalized Modules Membrane Antigens (GMMA), with...
ABSTRACT In the present study we evaluated role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background ( Igh-6 −/− ). immunized with live, attenuated aroA enterica serovar Typhimurium vaccine strain showed impaired long-term resistance against virulent C5. were able control primary and clear inoculum from reticuloendothelial system. However, mice, unlike +/+ controls, did not survive an oral challenge...
The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting bacterial counts spleens and livers of anti-IL-12-treated mice that 10- 100-fold higher than ones normally observed premortem mice; yet animals showed only signs illness. Nevertheless, they eventually died a slow, progressive disease. Mice infected with salmonellae become hypersusceptible endotoxin....
Salmonella enterica causes severe systemic diseases in humans and animals grows intracellularly within discrete tissue foci that become pathological lesions. Because of its lifestyle is a superb model for studying the vivo dynamics bacterial distribution. Using multicolour fluorescence microscopy mouse typhoid we have studied interaction between different populations same host as well dynamic evolution infection relation to growth localization. We showed liver results spread microorganisms...
Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine currently available. T cells important for clearance infection within macrophages, in Africa, invasive disease usually manifests the blood affects children between 4 months 2 y age, when anti- antibody absent. We have previously found a role complement-fixing bactericidal protecting these Here we show that opsonic...
The question of whether Ab responses to T-dependent Ags require B cell intrinsic signaling via the main TLR adaptor (MyD88) has become embroiled in confusion. In part this may be related methods used analyze signaling. We have a mixed bone marrow chimera model generate mice which compartment is completely deficient MyD88 expression, while other hematopoietic lineages are largely normal. These were immunized with or infected Salmonella. found that Ag-specific IgG2c primary response was...
Salmonella enterica causes a range of diseases. Salmonellae are intracellular parasites macrophages, and the control bacteria within these cells is critical to surviving an infection. The dynamics invading, surviving, proliferating in killing macrophages central disease pathogenesis. Fundamentally important parameters, however, such as cellular infection rate, have not previously been calculated. We used two independent approaches calculate macrophage rate: mathematical modelling...