RESUMEN
The development of anti-virulence drug therapy against Acinetobacter baumannii infections would provide an alternative to traditional antibacterial therapy that are increasingly failing. Here, we demonstrate that the OmpR transcriptional regulator plays a pivotal role in the pathogenesis of diverse A. baumannii clinical strains in multiple murine and G. mellonella invertebrate infection models. We identified OmpR-regulated genes using RNA sequencing and further validated two genes whose expression can be used as robust biomarker to quantify OmpR inhibition in A. baumannii. Moreover, the determination of the structure of the OmpR DNA binding domain of A. baumannii and the development of in vitro protein-DNA binding assays enabled the identification of an OmpR small molecule inhibitor. We conclude that OmpR is a valid and unexplored target to fight A. baumannii infections and we believe that the described platform combining in silico methods, in vitro OmpR inhibitory assays and in vivo G. mellonella surrogate infection model will facilitate future drug discovery programs.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Ratones , Animales , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Virulencia/genética , Antibacterianos/uso terapéuticoRESUMEN
The formation of persister cells is one mechanism by which bacteria can survive exposure to environmental stresses. We show that Campylobacter jejuni 11168H forms persister cells at a frequency of 10-3 after exposure to 100 × MIC of penicillin G for 24 h. Staining the cell population with a redox sensitive fluorescent dye revealed that penicillin G treatment resulted in the appearance of a population of cells with increased fluorescence. We present evidence, to show this could be a consequence of increased redox protein activity in, or associated with, the electron transport chain. These data suggest that a population of penicillin G treated C. jejuni cells could undergo a remodeling of the electron transport chain in order to moderate membrane hyperpolarization and intracellular alkalization; thus reducing the antibiotic efficacy and potentially assisting in persister cell formation.
Asunto(s)
Campylobacter jejuni , Antibacterianos/farmacología , Células Epiteliales , Oxidación-Reducción , Penicilinas/farmacologíaRESUMEN
In the past decade, Galleria mellonella (wax moth) larvae have become widely used as a non-mammalian infection model. However, the full potential of this infection model has yet to be realised, limited by the variable quality of larvae used and the lack of standardised procedures. Here, we review larvae suitable for research, protocols for dosing larvae, and methods for scoring illness in larvae infected with fungal pathogens. The development of standardised protocols for carrying out our experimental work will allow high throughput screens to be developed, changing the way in which we evaluate panels of mutants and strains. It will also enable the in vivo screening of potential antimicrobials at an earlier stage in the research and development cycle.
RESUMEN
The acute toxicities of 19 chemicals were assessed using G. mellonella larvae. The results obtained were compared against LD50 values derived from in vitro cytotoxicity tests and against in vivo acute oral LD50 values. In general, cell culture systems overestimated the toxicity of chemicals, especially low toxicity chemicals. In contrast, toxicity testing in G. mellonella larvae was found to be a reliable predictor for low toxicity chemicals. For the 9 chemicals tested which were assigned to Globally Harmonised System (GHS) category 5, the toxicity measured in G. mellonella larvae was consistent with their GHS categorisation but cytotoxicity measured in 3T3 or NHK cells predicted 4 out of 9 chemicals as having low toxicity. A more robust assessment of the likely toxicity of chemicals in mammals could be made by taking into account their toxicities in both cell cultures and in G. mellonella larvae.
Asunto(s)
Larva/efectos de los fármacos , Mariposas Nocturnas/efectos de los fármacos , Pruebas de Toxicidad/métodos , Animales , Línea Celular , Ratones , Células 3T3 NIHRESUMEN
Massively parallel sequencing technology coupled with saturation mutagenesis has provided new and global insights into gene functions and roles. At a simplistic level, the frequency of mutations within genes can indicate the degree of essentiality. However, this approach neglects to take account of the positional significance of mutations - the function of a gene is less likely to be disrupted by a mutation close to the distal ends. Therefore, a systematic bioinformatics approach to improve the reliability of essential gene identification is desirable. We report here a parametric model which introduces a novel mutation feature together with a noise trimming approach to predict the biological significance of Tn5 mutations. We show improved performance of essential gene prediction in the bacterium Yersinia pestis, the causative agent of plague. This method would have broad applicability to other organisms and to the identification of genes which are essential for competitiveness or survival under a broad range of stresses.
Asunto(s)
Proteínas Bacterianas/genética , Genes Esenciales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Peste/microbiología , Yersinia pestis/crecimiento & desarrollo , Yersinia pestis/genética , Biología Computacional , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Fenotipo , VirulenciaRESUMEN
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling. A comparison of our data with reported methylome changes in cells infected with M. tuberculosis revealed commonality of differentially methylated genes, including genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK), actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1), and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that pathogenic-specific and pathogen-common changes in the methylome occur following infection.
Asunto(s)
Infecciones por Burkholderia/genética , Burkholderia pseudomallei/patogenicidad , Metilación de ADN , Epigénesis Genética , Genoma Humano , Interacciones Huésped-Patógeno/genética , Leucemia/genética , Infecciones por Burkholderia/inmunología , Infecciones por Burkholderia/microbiología , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/crecimiento & desarrollo , Perfilación de la Expresión Génica , Humanos , Leucemia/microbiología , Leucemia/patología , Células Tumorales CultivadasRESUMEN
Mammals are widely used by microbiologists as a model host species to study infectious diseases of humans and domesticated livestock. These studies have been pivotal for our understanding of mechanisms of virulence and have allowed the development of diagnostics, pre-treatments and therapies for disease. However, over the past decade we have seen efforts to identify organisms which can be used as alternatives to mammals for these studies. The drivers for this are complex and multifactorial and include cost, ethical and scientific considerations. Galleria mellonella have been used as an alternative infection model since the 1980s and its utility for the study of bacterial disease and antimicrobial discovery was recently comprehensively reviewed. The wider applications of G. mellonella as a model host, including its susceptibility to 29 species of fungi, 7 viruses, 1 species of parasite and 16 biological toxins, are described in this perspective. In addition, the latest developments in the standardisation of G. mellonella larvae for research purposes has been reviewed.
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Infecciones , Modelos Animales , Mariposas Nocturnas/microbiología , Toxinas Biológicas , Animales , Antibacterianos/farmacología , Infecciones Bacterianas , Investigación Biomédica , Determinación de Punto Final , Interacciones Huésped-Patógeno , Larva/microbiología , Microbiota , Mariposas Nocturnas/virología , Micosis , Toxinas Biológicas/toxicidad , Virulencia , VirosisRESUMEN
There is an urgent need for an effective vaccine against human disease caused by Burkholderia pseudomallei, and although a wide range of candidates have been tested in mice none provide high level protection. We considered this might reflect the inability of these vaccine candidates to protect against chronic disease. Using Q-RT PCR we have identified 6 genes which are expressed in bacteria colonising spleens and lungs of chronically infected mice. Three of the genes (BPSL1897, BPSL3369 and BPSL2287) have been expressed in Escherichia coli and the encoded proteins purified. We have also included BPSL2765, a protein known to induce immune responses associated with a reduced incidence of chronic/recurrent disease in humans. Immunisation of mice with a combination of these antigens resulted in the induction of antibody responses against all of the proteins. Compared with mice immunised with capsular polysaccharide or LolC protein, mice immunised with the combination of chronic stage antigens showed enhanced protection against experimental disease in mice.
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Antígenos Bacterianos/inmunología , Vacunas Bacterianas/inmunología , Melioidosis/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Burkholderia pseudomallei/genética , Femenino , Genes Bacterianos , Inmunoglobulina G/sangre , Pulmón/microbiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo/microbiología , TranscriptomaRESUMEN
Burkholderia pseudomallei, the causative agent of melioidosis, has complex and poorly understood extracellular and intracellular lifestyles. We used transposon-directed insertion site sequencing (TraDIS) to retrospectively analyze a transposon library that had previously been screened through a BALB/c mouse model to identify genes important for growth and survival in vivo. This allowed us to identify the insertion sites and phenotypes of negatively selected mutants that were previously overlooked due to technical constraints. All 23 unique genes identified in the original screen were confirmed by TraDIS, and an additional 105 mutants with various degrees of attenuation in vivo were identified. Five of the newly identified genes were chosen for further characterization, and clean, unmarked bpsl2248, tex, rpiR, bpsl1728, and bpss1528 deletion mutants were constructed from the wild-type strain K96243. Each of these mutants was tested in vitro and in vivo to confirm their attenuated phenotypes and investigate the nature of the attenuation. Our results confirm that we have identified new genes important to in vivo virulence with roles in different stages of B. pseudomallei pathogenesis, including extracellular and intracellular survival. Of particular interest, deletion of the transcription accessory protein Tex was shown to be highly attenuating, and the tex mutant was capable of providing protective immunity against challenge with wild-type B. pseudomallei, suggesting that the genes identified in our TraDIS screen have the potential to be investigated as live vaccine candidates.
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Proteínas Bacterianas/metabolismo , Burkholderia pseudomallei/crecimiento & desarrollo , Burkholderia pseudomallei/metabolismo , Melioidosis/microbiología , Factores de Virulencia/metabolismo , Animales , Proteínas Bacterianas/genética , Burkholderia pseudomallei/genética , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Viabilidad Microbiana , Factores de Virulencia/genéticaRESUMEN
The enteropathogen Campylobacter jejuni is a global health disaster, being one of the leading causes of bacterial gastroenteritis. Here, we present the draft genome sequence of C. jejuni strain cj255, isolated from a chicken source in Islamabad, Pakistan. The draft genome sequence will aid in epidemiological studies and quarantine of this broad-host-range pathogen.
RESUMEN
BACKGROUND: Campylobacter jejuni and C. coli are human intestinal pathogens that are the most frequent causes of bacterial foodborne gastroenteritis in humans in the UK. In this study, we aimed to characterise the metabolic diversity of both C. jejuni and C. coli using a diverse panel of clinical strains isolated from the UK, Pakistan and Thailand, thereby representing both the developed and developing world. Our aim was to apply multi genome analysis and Biolog phenotyping to determine differences in carbon source utilisation by C. jejuni and C. coli strains. RESULTS: We have identified a core set of carbon sources (utilised by all strains tested) and a set that are differentially utilised for a diverse panel of thirteen C. jejuni and two C. coli strains. This study used multi genome analysis to show that propionic acid is utilised only by C. coli strains tested. A broader PCR screen of 16 C. coli strains and 42 C. jejuni confirmed the absence of the genes needed for propanoate metabolism. CONCLUSIONS: From our analysis we have identified a phenotypic method and two genotypic methods based on propionic utilisation that might be applicable for distinguishing between C. jejuni and C. coli.
Asunto(s)
Campylobacter coli/clasificación , Campylobacter coli/metabolismo , Campylobacter jejuni/clasificación , Campylobacter jejuni/metabolismo , Carbono/metabolismo , Propionatos/metabolismo , Técnicas de Tipificación Bacteriana/métodos , Infecciones por Campylobacter/microbiología , Campylobacter coli/aislamiento & purificación , Campylobacter jejuni/aislamiento & purificación , ADN Bacteriano/química , ADN Bacteriano/genética , Humanos , Redes y Vías Metabólicas/genética , Técnicas de Diagnóstico Molecular/métodos , Datos de Secuencia Molecular , Pakistán , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Tailandia , Reino UnidoRESUMEN
A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.
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Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/genética , Campylobacter jejuni/patogenicidad , Diarrea/epidemiología , Genoma Bacteriano , Carne/microbiología , Animales , Asia/epidemiología , Sistemas de Secreción Bacterianos/genética , Infecciones por Campylobacter/microbiología , Infecciones por Campylobacter/transmisión , Campylobacter jejuni/clasificación , Campylobacter jejuni/aislamiento & purificación , Pollos , Diarrea/microbiología , Humanos , Filogenia , Análisis de Secuencia de ADN , Reino Unido/epidemiología , VirulenciaRESUMEN
Burkholderia thailandensis, although normally avirulent for mammals, can infect macrophages in vitro and has occasionally been reported to cause pneumonia in humans. It is therefore used as a model organism for the human pathogen B. pseudomallei, to which it is closely related phylogenetically. We characterized the B. thailandensis clinical isolate CDC2721121 (BtCDC272) at the genome level and studied its response to environmental cues associated with human host colonization, namely, temperature and oxygen limitation. Effects of the different growth conditions on BtCDC272 were studied through whole genome transcription studies and analysis of proteins associated with the bacterial cell surface. We found that growth at 37°C, compared to 28°C, negatively affected cell motility and flagella production through a mechanism involving regulation of the flagellin-encoding fliC gene at the mRNA stability level. Growth in oxygen-limiting conditions, in contrast, stimulated various processes linked to virulence, such as lipopolysaccharide production and expression of genes encoding protein secretion systems. Consistent with these observations, BtCDC272 grown in oxygen limitation was more resistant to phagocytosis and strongly induced the production of inflammatory cytokines from murine macrophages. Our results suggest that, while temperature sensing is important for regulation of B. thailandensis cell motility, oxygen limitation has a deeper impact on its physiology and constitutes a crucial environmental signal for the production of virulence factors.
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Proteínas Bacterianas/genética , Burkholderia/crecimiento & desarrollo , Burkholderia/genética , Oxígeno/farmacología , Temperatura , Animales , Proteínas Bacterianas/metabolismo , Biopolímeros/metabolismo , Burkholderia/efectos de los fármacos , Burkholderia/ultraestructura , Comunicación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Genoma Bacteriano , Lipopolisacáridos/metabolismo , Ratones , Células Mieloides/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Adhesión en Parafina , Fagocitosis/efectos de los fármacos , Polihidroxialcanoatos/farmacología , Células RAW 264.7 , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN , Análisis de Secuencia de ARN , Factores de TiempoRESUMEN
We solved the crystal structure of Burkholderia pseudomallei acute phase antigen BPSL2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. Based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized to the same extent as the recombinant protein in sera from melioidosis-affected subjects. Antibodies raised against the consensus peptide were successfully tested in opsonization bacterial killing experiments and antibody-dependent agglutination tests of B. pseudomallei. Our strategy represents a step in the development of immunodiagnostics, in the production of specific antibodies and in the optimization of antigens for vaccine development, starting from structural and physicochemical principles.
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Antígenos Bacterianos/química , Proteínas Bacterianas/química , Vacunas Bacterianas/inmunología , Burkholderia pseudomallei/inmunología , Epítopos/química , Anticuerpos/sangre , Anticuerpos/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Burkholderia pseudomallei/metabolismo , Cristalografía por Rayos X , Mapeo Epitopo , Epítopos/inmunología , Epítopos/metabolismo , Humanos , Simulación de Dinámica Molecular , Neutrófilos/citología , Neutrófilos/inmunología , Fagocitosis , Estructura Terciaria de Proteína , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunologíaRESUMEN
BACKGROUND: In order to identify new virulence determinants in Y. pseudotuberculosis a comparison between its genome and that of Yersinia pestis was undertaken. This reveals dozens of pseudogenes in Y. pestis, which are still putatively functional in Y. pseudotuberculosis and may be important in the enteric lifestyle. One such gene, YPTB1572 in the Y. pseudotuberculosis IP32953 genome sequence, encodes a protein with similarity to invasin, a classic adhesion/invasion protein, and to intimin, the attaching and effacing protein from enteropathogenic (EPEC) and enterohaemorraghic (EHEC) Escherichia coli. RESULTS: We termed YPTB1572 Ifp (Intimin family protein) and show that it is able to bind directly to human HEp-2 epithelial cells. Cysteine and tryptophan residues in the C-terminal region of intimin that are essential for function in EPEC and EHEC are conserved in Ifp. Protein binding occurred at distinct foci on the HEp-2 cell surface and can be disrupted by mutation of a single cysteine residue at the C-terminus of the protein. Temporal expression analysis using lux reporter constructs revealed that ifp is expressed at late log phase at 37°C in contrast to invasin, suggesting that Ifp is a late stage adhesin. An ifp defined mutant showed a reduction in adhesion to HEp-2 cells and was attenuated in the Galleria mellonella infection model. CONCLUSION: A new Y. pseudotuberculosis adhesin has been identified and characterised. This Ifp is a new member in the family of invasin/intimin outer membrane adhesins.
Asunto(s)
Adhesinas Bacterianas/genética , Adhesinas Bacterianas/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/patogenicidad , Sustitución de Aminoácidos/genética , Animales , Adhesión Bacteriana , Línea Celular , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Hepatocitos/microbiología , Humanos , Lepidópteros/microbiología , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Unión Proteica , Análisis de SupervivenciaRESUMEN
Larvae of Galleria mellonella (Greater Wax Moth) have been shown to be susceptible to Campylobacter jejuni infection and our study characterizes this infection model. Following infection with C. jejuni human isolates, bacteria were visible in the haemocoel and gut of challenged larvae, and there was extensive damage to the gut. Bacteria were found in the extracellular and cell-associated fraction in the haemocoel, and it was shown that C. jejuni can survive in insect cells. Finally, we have used the model to screen a further 67 C. jejuni isolates belonging to different MLST types. Isolates belonging to ST257 were the most virulent in the Galleria model, whereas those belonging to ST21 were the least virulent.
Asunto(s)
Infecciones por Campylobacter/etiología , Campylobacter jejuni/patogenicidad , Mariposas Nocturnas/microbiología , Animales , Técnicas de Tipificación Bacteriana , Campylobacter jejuni/clasificación , Campylobacter jejuni/genética , Campylobacter jejuni/aislamiento & purificación , Línea Celular , Modelos Animales de Enfermedad , Hemocitos/microbiología , Humanos , Larva/microbiología , Macrófagos/microbiología , Ratones , Tipificación de Secuencias Multilocus , Spodoptera/microbiología , Virulencia/genéticaRESUMEN
Manganese has an important yet undefined role in the virulence of many bacterial pathogens. In this study we confirm that a null mutation in Yersinia pseudotuberculosis mntH reduces intracellular manganese accumulation. An mntH mutant was susceptible to killing by reactive oxygen species when grown under manganese-limited conditions. The mntH mutant was defective in survival and growth in macrophages expressing functional Nramp1, but in macrophages deficient in Nramp the bacteria were able to survive and replicate. In Galleria mellonella, the mntH mutant was attenuated. Taken together, these data suggest a role for manganese in Y. pseudotuberculosis during macrophage intracellular survival, protecting the bacteria from the antimicrobial products released during the respiratory burst.
Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas de Transporte de Catión/metabolismo , Macrófagos/microbiología , Manganeso/metabolismo , Viabilidad Microbiana , Yersinia pseudotuberculosis/fisiología , Animales , Proteínas Bacterianas/genética , Proteínas de Transporte de Catión/genética , Línea Celular , Técnicas de Inactivación de Genes , Prueba de Complementación Genética , Lepidópteros/microbiología , Ratones , Estrés Oxidativo , Especies Reactivas de Oxígeno/toxicidad , Análisis de Supervivencia , Virulencia , Yersinia pseudotuberculosis/efectos de los fármacos , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/metabolismoRESUMEN
Galleria mellonella (wax moth) larvae have elsewhere been shown to be susceptible to pathogens such as Francisella tularensis, Burkholderia mallei, and Pseudomonas aeruginosa. We report that the larvae are rapidly killed by Campylobacter jejuni at 37C. Three strains of C. jejuni tested, 11168H (human diarrheal isolate), G1 (human Guillain-Barré syndrome isolate), and 81-176 (human diarrheal isolate), were equally effective at killing G. mellonella larvae. A panel of defined mutants of C. jejuni 11168H, in known or putative virulence genes, showed different degrees of attenuation in G. mellonella larvae. A mutant lacking the O-methyl phosphoramidate (MeOPN) capsule side group was attenuated, clearly demonstrating that MeOPN has a role in virulence. This new model of C. jejuni infection should facilitate the identification of novel virulence genes.
Asunto(s)
Amidas/toxicidad , Infecciones por Campylobacter/microbiología , Campylobacter jejuni/patogenicidad , Modelos Animales de Enfermedad , Mariposas Nocturnas/efectos de los fármacos , Ácidos Fosfóricos/toxicidad , Animales , Técnicas de Inactivación de Genes , Humanos , Larva/efectos de los fármacos , Larva/microbiología , Mariposas Nocturnas/microbiología , Análisis de Supervivencia , Temperatura , Virulencia , Factores de Virulencia/genéticaRESUMEN
We report that larvae of the wax moth (Galleria mellonella) are susceptible to infection with the human enteropathogen Yersinia pseudotuberculosis at 37 degrees C. Confocal microscopy demonstrated that in the initial stages of infection the bacteria were taken up into haemocytes. To evaluate the utility of this model for screening Y. pseudotuberculosis mutants we constructed and tested a superoxide dismutase C (sodC) mutant. This mutant showed increased susceptibility to superoxide, a key mechanism of killing in insect haemocytes and mammalian phagocytes. It showed reduced virulence in the murine yersiniosis infection model and in contrast to the wild-type strain IP32953 was unable to kill G. mellonella. The complemented mutant regained all phenotypic properties associated with SodC, confirming the important role of this metalloenzyme in two Y. pseudotuberculosis infection models.
Asunto(s)
Modelos Animales de Enfermedad , Mariposas Nocturnas , Infecciones por Yersinia pseudotuberculosis/microbiología , Yersinia pseudotuberculosis/patogenicidad , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Mariposas Nocturnas/microbiología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Virulencia , Yersinia pseudotuberculosis/enzimología , Yersinia pseudotuberculosis/genéticaRESUMEN
We tested the hypothesis that host resistance to Campylobacter jejuni is Nramp1 dependent. Following intraperitoneal (IP) inoculation of Nramp1+/+ and isogenic Nramp1-deficient (Nramp1-/-) mice C. jejuni primarily associated with mac1-positive cells in liver tissue. A significant reduction of C. jejuni was observed in Nramp1+/+ mice 4 days post-infection (PI) (liver) and 8 days PI cecum-colon. In contrast, Nramp1-/- mice showed no significant reduction of C. jejuni and instead had a chronic inflammatory response and significant histopathological lesions 30 days PI. Differential cytokine profiles were observed in C. jejuni infected Nramp1+/+ and Nramp1-/- primary dendritic cells. Taken together these data indicate that Nramp1 is critical for host resistance to C. jejuni.