inducing-meningococcal-meningitis-serogroup-c-mice-via-intracisternal

Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery

Neisseria meningitidis (meningococcus) is a narrow-host-range microorganism, globally recognized as the leading cause of bacterial meningitis. ...

University of Naples Federico II

Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.

Impairment of circulating endothelial progenitors in Down syndrome.

Bartonella henselae is able to internalize endothelial progenitor cells (EPCs), which are resistant to the infection of other common pathogens. Bacteroides fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects from experimental colitis induced by Helicobacter hepaticus through the polysaccharide A (PSA). The aim of our study was to establish: 1) whether B. fragilis colonization could protect from B. henselae infection; if this event may have beneficial effects on EPCs, vascular system and tissues. Our in vitro results establish for the first time that B. fragilis can internalize EPCs and competes with B. henselae during coinfection. We observed a marked activation of the inflammatory response by Real-time PCR and ELISA in coinfected cells compared to B. henselae-infected cells (63 vs 23 up-regulated genes), and after EPCs infection with mutant B. fragilis ΔPSA (≅90% up-regulated genes) compared to B. fragilis. Interestingly, in a mouse model of coinfection, morphological and ultrastructural analyses by hematoxylin-eosin staining and electron microscopy on murine tissues revealed that damages induced by B. henselae can be prevented in the coinfection with B. fragilis but not with its mutant B. fragilis ΔPSA. Moreover, immunohistochemistry analysis with anti-Bartonella showed that the number of positive cells per field decreased of at least 50% in the liver (20±4 vs 50±8), aorta (5±1 vs 10±2) and spleen (25±3 vs 40±6) sections of mice coinfected compared to mice infected only with B. henselae. This decrease was less evident in the coinfection with ΔPSA strain (35±6 in the liver, 5±1 in the aorta and 30±5 in the spleen). Finally, B. fragilis colonization was also able to restore the EPC decrease observed in mice infected with B. henselae (0.65 vs 0.06 media). Thus, our data establish that B. fragilis colonization is able to prevent B. henselae damages through PSA.

Evidence of Bacteroides fragilis protection from Bartonella henselae-induced damage.

Cardiovascular disease is still the major cause of death worldwide despite the remarkable progress in its prevention and treatment. Endothelial progenitor cells (EPCs) have recently emerged as key players of vascular repair and regenerative medicine applied to cardiovascular disease. A large amount of effort has been put into discovering the factors that could aid or impair the number and function of EPCs, and also into characterizing these cells at the molecular level in order to facilitate their therapeutic applications in vascular disease. Interestingly, the major cardiovascular risk factors have been associated with reduced number and function of EPCs. The bacterial contribution to cardiovascular disease represents a long-standing controversy. The discovery that Bartonella henselae can infect and damage EPCs revitalizes the enduring debate about the microbiological contribution to atherosclerosis, thus allowing the hypothesis that this infection could impair the cardiovascular regenerative potential and increase the risk for cardiovascular disease. In this review, we summarize the rationale suggesting that Bartonella henselae could favour atherogenesis by infecting and damaging EPCs, thus reducing their vascular repair potential. These mechanisms suggest a novel link between communicable and non-communicable human diseases, and put forward the possibility that Bartonella henselae could enhance the susceptibility and worsen the prognosis in cardiovascular disease. 

Infections and cardiovascular disease: is Bartonella henselae contributing to this matter?

Celiac disease (CD)-associated duodenal dysbiosis has not yet been clearly defined, and the mechanisms by which CD-associated dysbiosis could concur to CD development or exacerbation are unknown. In this study, we analyzed the duodenal microbiome of CD patients.

Metagenomics Reveals Dysbiosis and a Potentially Pathogenic N. flavescens Strain in Duodenum of Adult Celiac Patients.

No Change in the Mucosal Gut Mycobioma Is Associated with Celiac Disease-Specific Microbiome Alteration in Adult Patients.

 is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that  colonization is able to prevent  damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of  in immunocompromised hosts, SCID mice were co-infected with  wild type or its mutant  ΔPSA and the effects of infection on murine tissues have been observed by High-Frequency Ultrasound (HFUS), histopathological examination, and Transmission Electron Microscopy (TEM). For the first time, echostructure, hepatic lobes length, vascular alterations, and indirect signs of hepatic dysfunctions, routinely used as signs of disease in humans, have been analyzed in an immunocompromised murine model. Our findings showed echostructural alterations in all infected mice compared with the Phosphate Buffer Solution (PBS) control group; further, those infected with  and co-infected with  ΔPSA presented the major echostructural alterations. Half of the mice infected with  and all those co-infected with  ΔPSA have showed an altered hepatic echogenicity compared with the renal cortex. The echogenicity score of co-infected mice with  ΔPSA differed significantly compared with the PBS control group (p < 0.05). Moreover the inflammation score of the histopathological evaluation was fairly concordant with ultrasound findings. Ultrastructural analysis performed by TEM revealed no significant alterations in liver samples of SCID mice infected with  wild type while those infected with  ΔPSA showed the presence of collagen around the main vessels compared with the PBS control group. The liver samples of mice infected with  showed macro-areas rich in collagen, stellate cells, and histiocytic cells. Interestingly, our data demonstrated that immunocompromised SCID mice infected with  and co-infected with  ΔPSA showed the most severe morpho-structural liver damage. In addition, these results suggests that the HFUS together with histopathological evaluation could be considered good imaging approach to evaluate hepatic alterations.

Novel Approach for Evaluation of  Protective Role against  Liver Damage in Immunocompromised Murine Model.

This report describes a case of congenital toxoplasmosis in a newborn in Southern Italy. A pregnant mother had been admitted at the 20th week of her pregnancy on account of pharyngodynia and laterocervical lymphadenopathy. Although serological testing of the mother's serum documented a seroconversion with positive IgG and IgM anti-Toxoplasma antibodies during II trimester, the woman refused to perform prenatal diagnosis for congenital toxoplasmosis. Fetal ultrasound scan already showed mild asymmetrical triventricular hydrocephaly and cerebral calcifications. After birth, real-time PCR on cerebrospinal fluid and blood samples of the newborn showed a positive result for 529bp-repeat element DNA of T. gondii, In addition brain magnetic resonance imaging and computed tomography showed a characteristic diffuse brain tissue loss associated with hydrocephalus. For the first time molecular characterization of T. gondii isolate was performed directly from the newborn's CSF samples by using nested-PCR-RFLP of sag-2 and pk1 genes. The PCR-RLFP analysis revealed that the isolate belongs to the clonal type II, the predominant lineage causing human toxoplasmosis, as confirmed by DNA sequencing.

Genotyping of Toxoplasma gondii strain directly from human CSF samples of congenital toxoplasmosis clinical case.

To evaluate the antimicrobial activity of hydroalcoholic extracts of pomegranate ( L.) peel and juice, against the microorganisms considered the main etiologic agents of dental caries.

 Antibacterial Activity of Pomegranate Juice and Peel Extracts on Cariogenic Bacteria.

We previously profiled duodenal microbiome in active (a-), gluten-free diet (GFD) celiac disease (CD) patients and controls finding higher levels of the Proteobacterium Neisseria flavescens in a-CD patients than in the other two groups. Here, we investigate the oropharyngeal microbiome in CD patients and controls to evaluate whether this niche share microbial composition with the duodenum. We characterized by 16S rRNA gene sequencing the oropharyngeal microbiome in 14 a-CD, 22 GFD patients and 20 controls. Bacteroidetes, Proteobacteria and Firmicutes differed significantly between the three groups. In particular, Proteobacteria abounded in a-CD and Neisseria species mostly accounted for this abundance (p < 0.001), whereas Bacteroidetes were more present in control and GFD microbiomes. Culture-based oropharyngeal microbiota analysis confirmed the greater abundance of Proteobacteria and of Neisseria species in a-CD. Microbial functions prediction indicated a greater metabolic potential for degradation of aminoacids, lipids and ketone bodies in a-CD microbiome than in control and GFD microbiomes, in which polysaccharide metabolism predominated. Our results suggest a continuum of a-CD microbial composition from mouth to duodenum. We may speculate that microbiome characterization in the oropharynx, which is a less invasive sampling than the duodenum, could contribute to investigate the role of dysbiosis in CD pathogenesis.

Article	Year
Impairment of circulating endothelial progenitors in Down syndrome. BMC medical genomics\| PubMed ID: 20836844	2010
Evidence of Bacteroides fragilis protection from Bartonella henselae-induced damage. PloS one\| PubMed ID: 23166739	2012
Infections and cardiovascular disease: is Bartonella henselae contributing to this matter? Journal of medical microbiology\| PubMed ID: 26066633	2015
Metagenomics Reveals Dysbiosis and a Potentially Pathogenic N. flavescens Strain in Duodenum of Adult Celiac Patients. The American journal of gastroenterology\| PubMed ID: 27045926	2016
No Change in the Mucosal Gut Mycobioma Is Associated with Celiac Disease-Specific Microbiome Alteration in Adult Patients. The American journal of gastroenterology\| PubMed ID: 27808136	2016
Novel Approach for Evaluation of Protective Role against Liver Damage in Immunocompromised Murine Model. Frontiers in microbiology\| PubMed ID: 27872616	2016
Genotyping of Toxoplasma gondii strain directly from human CSF samples of congenital toxoplasmosis clinical case. The new microbiologica\| PubMed ID: 28368078	2017
Antibacterial Activity of Pomegranate Juice and Peel Extracts on Cariogenic Bacteria. BioMed research international\| PubMed ID: 29209624	2017
Oropharyngeal microbiome evaluation highlights Neisseria abundance in active celiac patients. Scientific reports\| PubMed ID: 30038321	2018

Roberta Colicchio

Biography

JoVE Journal Publications

Other Publications