A5004721023- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immunodeficiency and Autoimmune Disorders
- Antibiotic Resistance in Bacteria
- Antifungal resistance and susceptibility
- Bacteriophages and microbial interactions
- Antimicrobial Peptides and Activities
- Fungal Infections and Studies
- Immune responses and vaccinations
- Diagnosis and treatment of tuberculosis
- Immune Response and Inflammation
- Biosensors and Analytical Detection
- Analytical Chemistry and Sensors
- Pneumocystis jirovecii pneumonia detection and treatment
- Biochemical and Structural Characterization
- Bacterial biofilms and quorum sensing
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Gut microbiota and health
- vaccines and immunoinformatics approaches
- Electrochemical Analysis and Applications
- T-cell and B-cell Immunology
- Advanced Sensor and Energy Harvesting Materials
- Infectious Diseases and Tuberculosis
- Fungal and yeast genetics research
University of Pisa
2014-2023
Whitehead Institute for Biomedical Research
2019
Institut Pasteur
2007-2015
Mycobacterium species, including tuberculosis and leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged paradigm that these pathogens exclusively localize within phagosome host cells. As yet biological relevance mycobacterial translocation to cytosol remained unclear. In this current study we used electron microscopy techniques establish a clear link between virulence. Pathogenic, patient-derived species were found translocate...
ABSTRACT The 6-kDa early secreted antigenic target ESAT-6 and the 10-kDa culture filtrate protein CFP-10 of Mycobacterium tuberculosis are by ESX-1 system into host cell thereby contribute to pathogenicity. Although different studies performed at organismal cellular levels have helped explain ESX-1-associated phenomena, not much is known about how pathogenesis molecular level. In this study we describe interaction both proteins with lipid bilayers, using biologically relevant liposomal...
Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two the most widely used attenuated history research are Mycobacterium bovis BCG (BCG) H37Ra (H37Ra), which both during vitro serial passage. Whereas attenuation due mainly loss ESAT-6 secretion system, ESX-1, reason why remained unknown. However, here we show point mutation (S219L) predicted DNA...
The dedicated secretion system ESX-1 of Mycobacterium tuberculosis encoded by the extended RD1 region (extRD1) assures export ESAT-6 protein and its partner, 10-kDa culture filtrate CFP-10, is missing from vaccine strains M. bovis BCG microti. Here, we systematically investigated involvement each individual gene in both antigens, specific immunogenicity, virulence. ESX-1-complemented microti were more efficiently engulfed bone-marrow-derived macrophages than controls, this may account for...
Summary The chromosome of Mycobacterium tuberculosis encodes five type VII secretion systems (ESX‐1–ESX‐5). While the role ESX‐1 and ESX‐3 in M. has been elucidated, predictions for function ESX‐5 system came from data obtained marinum , where it transports PPE PE_PGRS proteins modulates innate immune responses. To define this study, we have constructed H37Rv knockout/deletion mutants, inactivating eccA 5 eccD rv1794 esxM genes or ppe25‐pe19 region. Whereas Mtb ko displayed no obvious...
Mycobacterium tuberculosis is an intracellular pathogen. Within macrophages, M. thrives in a specialized membrane-bound vacuole, the phagosome, whose pH slightly acidic, and where access to nutrients limited. Understanding how bacillus extracts incorporates from its host may help develop novel strategies combat tuberculosis. Here we show that employs asparagine transporter AnsP2 secreted asparaginase AnsA assimilate nitrogen resist acid stress through hydrolysis ammonia release. While role...
Abstract Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted “modern” responsible for globally-spread epidemics, whereas TbD1-intact “ancestral” tend to be restricted specific geographical areas, such as South India and East Asia (L1) or Africa (L7). By constructing characterizing panel...
The antimicrobial activity of human beta-defensin 3 (hBD-3) against multidrug-resistant clinical isolates Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) all bacterial strains tested observed. presence 20% serum abolished the hBD-3 gram-negative reduced peptide gram-positive strains.
Abstract We have previously demonstrated that a soluble form of the human NK cell natural cytotoxicity receptor p44, binds to surface M ycobacterium tuberculosis ( MTB ). Herein, we investigated interaction wall components CWC ) with p44 or T oll‐like 2 TLR 2) and role in direct activation cells upon stimulation . By using several purified bacterial an ELISA , was able bind core mycolyl‐arabinogalactan‐peptidoglycan mAGP as well mycolic acids MA arabinogalactan AG ), while bound...
Staphylococcus epidermidis plays a major role in biofilm-related medical device infections. Herein the anti-biofilm activity of human liver-derived antimicrobial peptide hepcidin 20 (hep20) was evaluated against polysaccharide intercellular adhesin (PIA)-positive and PIA-negative clinical isolates S. epidermidis. Hep20 markedly inhibited biofilm formation bacterial cell metabolism PIA-positive strains, but decrease biomass only partially correlated with viable bacteria. Confocal microscope...
The pathogenesis of Mycobacterium tuberculosis largely depends on the secretion 6-kD early secreted antigenic target ESAT-6 (EsxA) and 10-kD culture filtrate protein CFP-10 (EsxB) via ESX-1/typeVII system. Although gene products from core RD1 region have been shown to be deeply implicated in this process, less is known about proteins encoded further upstream 5' ESX-1 cluster, such as secretion-associated (Esps) EspF or EspG(1).To elucidate role EspF/G(1), whose orthologs marinum smegmatis...
Mycobacterium tuberculosis (Mtb), possesses at least three type VII secretion systems, ESX-1, -3 and -5 that are actively involved in pathogenesis host-pathogen interaction. We recently showed an attenuated Mtb vaccine candidate (Mtb Δppe25-pe19), which lacks the characteristic ESX-5-associated pe/ppe genes, but harbors all other components of ESX-5 system, induces CD4+ T-cell immune responses against non-esx-5-associated PE/PPE protein homologs. These T cells strongly cross-recognize...
The in vitro activities of human beta-defensin 3 (hBD-3) alone or combined with lysozyme, metronidazole, amoxicillin, and chlorhexidine were investigated the oral bacteria Streptococcus mutans, sanguinis, sobrinus, Lactobacillus acidophilus, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis. hBD-3 showed bactericidal activity against all bacterial species tested. effect was enhanced when peptide used combination antimicrobial agents mentioned above.
Abstract Mycobacterium bovis bacillus Calmette‐Guérin (BCG) is capable of directly stimulating several effector functions human natural killer (NK) cells in the absence interleukin‐12 and professional antigen presenting cells. To assess contribution two main NK‐cell subsets (CD56 dim CD56 bright ) to overall vitro response BCG, peripheral blood mononuclear depleted nylon wool‐adherent or purified NK were stimulated with live BCG. By combining intranuclear bromodeoxyuridine (BrdU) staining...
The recently described ESX-5 secretion system of Mycobacterium tuberculosis is one the most important modulators host-pathogen interactions due to its crucial impact on PPE protein secretion, cell wall stability and virulence. Although various components machinery have been defined, other core still remain be characterized. In this study, we focused EccB5 EccC5, a transmembrane (EccB5) membrane-bound ATPase (EccC5), both predicted building blocks M. membrane-associated complex. vitro...