Silvia Caterina Resta

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Department of Experimental Medicine
University of Salento

Silvia Caterina Resta


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https://researchid.co/silviacaterinaresta

RESEARCH, TEACHING, or OTHER INTERESTS

Applied Microbiology and Biotechnology, Cell Biology
10

Scopus Publications

81

Scholar Citations

5

Scholar h-index

4

Scholar i10-index

Scopus Publications

  • Effects of surface-exposed sialic acid and LOS outer core on the ability of native Neisseria meningitidis outer membrane vesicles (nOMVs) to induce cytokine expression and pyroptotic pathways in THP-1-derived macrophages
    Silvia Caterina Resta, Adelfia Talà, Antonio Baccante, Giovanni Saudino, Pasquale Petruccelli, Vito Di Cioccio, Cecilia Bucci, Pietro Alifano
    Scientific Reports, 2026
    Native outer membrane vesicles (nOMVs) are involved in meningococcal pathogenesis and are used for vaccine production. In this study, macrophages derived from the human monocytic cell line THP-1 were exposed to nOMVs from serogroup B N. meningitidis B1940 and derivative mutants B1940 siaD(+C), lacking the capsule, and B1940 cps, lacking both the capsule and the LOS outer core with sialic acid. Compared with THP-1 cells exposed to B1940 nOMVs, cells exposed to B1940 cps nOMVs showed significantly lower mRNA levels of genes encoding chemokines, interleukins, caspases, and gasdermin E (DFNA5). Furthermore, Western blot analysis showed a reduction in pro-IL-1β expression and activation of gasdermin E and caspase-4 in THP-1 macrophages treated with B1940 cps nOMVs compared to B1940 or B1940 siaD(+C) nOMVs. However, secreted pro-IL-1β and IL-1β were detected in the culture medium of THP-1 cells exposed to B1940 siaD(+C) nOMVs but not to B1940 or B1940 cps nOMVs. These findings provide genetic evidence that surface-exposed sialic acid and LOS outer core may contribute to the ability of meningococcal nOMVs to activate cytokine expression and pyroptotic pathways in THP-1-derived macrophages, providing new information to create safe nOMV-based vaccines.
  • Propionic acid toxicity and utilization of α-ketobutyric acid in Neisseria meningitidis via the methylcitrate cycle under specific conditions
    Adelfia Talà, Matteo Calcagnile, Silvia Caterina Resta, Salvatore Maurizio Tredici, Giuseppe Egidio De Benedetto, Cecilia Bucci, Pietro Alifano
    Microbiology Spectrum, 2025
    Neisseria meningitidis is a human-specific, transient colonizer of the nasopharynx that occasionally causes invasive disease. It can utilize a limited range of compounds as primary carbon sources, including glucose, maltose, lactate, and pyruvate, which are present in varying concentrations in microenvironments relevant to meningococcal infection. Additionally, intermediates from the tricarboxylic acid cycle, such as succinate, fumarate, and malate, as well as amino acids like glutamate, are utilized as supplementary carbon sources. Notably, N. meningitidis also possesses a functional methylcitrate cycle (MCC), which enables the assimilation of propionic acid and mitigates its toxicity. In this study, we investigated propionate toxicity and MCC functionality in wild-type N. meningitidis strains and prpB -, prpC -, ackA1- , and ackA2 -defective mutants under various growth conditions. We observed that propionate toxicity was influenced by the primary carbon source and additional factors, such as bicarbonate. Specifically, prpB - and prpC -defective mutants showed high sensitivity to propionate when cultured with glucose or pyruvate, but were not inhibited even by high concentrations of propionate when grown with lactate. The mechanisms underlying the conditional toxicity of propionate were further explored and discussed. Additionally, in the genome of 41 out of 128 N . meningitidis strains, we identified a gene encoding a transporter from the 4-toluene sulfonate uptake permease family, located between prpC and acnD in the MCC gene cluster. Genetic inactivation of this gene, named kbuT , impaired the ability to take up and oxidize α-ketobutyrate, an α-keto acid abundant in host cells, which can be used as a carbon source through the MCC. IMPORTANCE Meningococci are metabolically versatile organisms, switching between intracellular and extracellular lifestyle during colonization and invasive disease. Niche switching impacts on how bacteria communicate with host to find a balance between nutrient assimilation and protection against toxicity of some metabolites. The methylcitrate pathway fulfills this function, providing a compromise between propionate assimilation and propionate detoxification, in relation to the colonized host microenvironments. In this study, we revealed an unexpected difference in the sensitivity of meningococci to propionate when grown with different carbon sources. We also characterized the function of a gene located within the prp operon that encodes a transporter of α-ketobutyrate, an α-ketoacid abundant in host cells. These results contribute to extending our understanding of the metabolic adaptation mechanisms, which are crucial for meningococcal infection and virulence within the host microenvironments.
  • Neisseria meningitidis: a traditional extracellular pathogen with an intense intracellular lifestyle
    Silvia Caterina Resta, Adelfia Talà, Riccardo Conte, Matteo Calcagnile, Cecilia Bucci, Pietro Alifano
    Frontiers in Cellular and Infection Microbiology, 2025
    Neisseria meningitidis (meningococcus) is a transitory colonizer of the human nasopharynx that occasionally, for largely unknown reasons, reaches the bloodstream, translocating across the nasopharyngeal mucosa, causing septicemia. The bloodstream spread of bacteria to the meninges can cause meningitis after crossing the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Thus, the meningococcus must cross several epithelial and endothelial barriers to cause invasive meningococcal disease (IMD). While meningococcal interactions on the surface of epithelial and endothelial cells have been intensively investigated, leading to the identification of key determinants of virulence of this bacterium, relatively little is known about the crossing of the nasopharyngeal epithelial barrier (NEB), the BBB, and BCSFB by the meningococcus. Several mechanisms (transcellular and paracellular) have been proposed, including transcellular crossing and paracellular crossing that might be favored by an epicellular lifestyle of this bacterium. Little is also known about the prevalent (vacuolar or cytoplasmic) localization of N. meningitidis in infected epithelial and endothelial cells and the mechanisms adopted by this microorganism to survive and multiply in the intracellular environment. The purpose of this article is to collect and review what is actually known about the intracellular lifestyle of these microorganisms. The picture that emerges is that although it is traditionally considered an extracellular pathogen (despite its original name, Diplococcus intracellularis meningitidis [Weichseilbaum, 1887]), N. meningitidis engages in complex interactions with host cells in the intracellular microenvironment, involving signal transduction, membrane trafficking, cytoskeleton, metabolic cross-talk, and programmed cell death.
  • Beyond Inflammation: Role of Pyroptosis Pathway Activation by Gram-Negative Bacteria and Their Outer Membrane Vesicles (OMVs) in the Interaction with the Host Cell
    Silvia Caterina Resta, Flora Guerra, Adelfia Talà, Cecilia Bucci, Pietro Alifano
    Cells, 2024
    Pyroptosis is a gasdermin-mediated pro-inflammatory programmed cell death that, during microbial infections, aims to restrict the spreading of bacteria. Nevertheless, excessive pyroptosis activation leads to inflammation levels that are detrimental to the host. Pathogen-associated molecular patterns (PAMPs) present in bacteria and outer membrane vesicles (OMVs) can trigger pyroptosis pathways in different cell types with different outcomes. Moreover, some pathogens have evolved virulence factors that directly interfere with pyroptosis pathways, like Yersinia pestis YopM and Shigella flexneri IpaH7.8. Other virulence factors, such as those of Neisseria meningitidis, Neisseria gonorrhoeae, Salmonella enterica, and Helicobacter pylori affect pyroptosis pathways indirectly with important differences between pathogenic and commensal species of the same family. These pathogens deserve special attention because of the increasing antimicrobial resistance of S. flexneri and N. gonorrhoeae, the high prevalence of S. enterica and H. pylori, and the life-threatening diseases caused by N. meningitidis and Y. pestis. While inflammation due to macrophage pyroptosis has been extensively addressed, the effects of activation of pyroptosis pathways on modulation of cell cytoskeleton and cell–cell junctions in epithelia and endothelia and on the bacterial crossing of epithelial and endothelial barriers have only been partly investigated. Another important point is the diverse consequences of pyroptosis pathways on calcium influx, like activation of calcium-dependent enzymes and mitochondria dysregulation. This review will discuss the pyroptotic pathways activated by Gram-negative bacteria and their OMVs, analyzing the differences between pathogens and commensal bacteria. Particular attention will also be paid to the experimental models adopted and the main results obtained in the different models. Finally, strategies adopted by pathogens to modulate these pathways will be discussed with a perspective on the use of pyroptosis inhibitors as adjuvants in the treatment of infections.
  • Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system
    Chiara Pagliuca, Roberta Colicchio, Silvia Caterina Resta, Adelfia Talà, Elena Scaglione, Giuseppe Mantova, Leonardo Continisio, Caterina Pagliarulo, Cecilia Bucci, Pietro Alifano, Paola Salvatore
    Frontiers in Cellular and Infection Microbiology, 2024
    There is evidence that in infected cells in vitro the meningococcal HrpA/HrpB two-partner secretion system (TPS) mediates the exit of bacteria from the internalization vacuole and the docking of bacteria to the dynein motor resulting in the induction of pyroptosis. In this study we set out to study the role of the HrpA/HrpB TPS in establishing meningitis and activating pyroptotic pathways in an animal model of meningitis using a reference serogroup C meningococcal strain, 93/4286, and an isogenic hrpB knockout mutant, 93/4286ΩhrpB. Survival experiments confirmed the role of HrpA/HrpB TPS in the invasive meningococcal disease. In fact, the ability of the hrpB mutant to replicate in brain and spread systemically was impaired in mice infected with hrpB mutant. Furthermore, western blot analysis of brain samples during the infection demonstrated that: i. N. meningitidis activated canonical and non-canonical inflammasome pyroptosis pathways in the mouse brain; ii. the activation of caspase-11, caspase-1, and gasdermin-D was markedly reduced in the hrpB mutant; iii. the increase in the amount of IL-1β and IL-18, which are an important end point of pyroptosis, occurs in the brains of mice infected with the wild-type strain 93/4286 and is strongly reduced in those infected with 93/4286ΩhrpB. In particular, the activation of caspase 11, which is triggered by cytosolic lipopolysaccharide, indicates that during meningococcal infection pyroptosis is induced by intracellular infection after the exit of the bacteria from the internalizing vacuole, a process that is hindered in the hrpB mutant. Overall, these results confirm, in an animal model, that the HrpA/HrpB TPS plays a role in the induction of pyroptosis and suggest a pivotal involvement of pyroptosis in invasive meningococcal disease, paving the way for the use of pyroptosis inhibitors in the adjuvant therapy of the disease.
  • Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae
    Adelfia Talà, Matteo Calcagnile, Silvia Caterina Resta, Antonio Pennetta, Giuseppe Egidio De Benedetto, Pietro Alifano
    Frontiers in Microbiology, 2023
    Due to the increased resistance to all available antibiotics and the lack of vaccines, Neisseria gonorrhoeae (the gonococcus) poses an urgent threat. Although the mechanisms of virulence and antibiotic resistance have been largely investigated in this bacterium, very few studies have addressed the stringent response (SR) that in pathogenic bacteria controls the expression of genes involved in host-pathogen interaction and tolerance and persistence toward antibiotics. In this study, the results of the transcriptome analysis of a clinical isolate of N. gonorrhoeae, after induction of the SR by serine hydroxamate, provided us with an accurate list of genes that are transcriptionally modulated during the SR. The list includes genes associated with metabolism, cellular machine functions, host-pathogen interaction, genome plasticity, and antibiotic tolerance and persistence. Moreover, we found that the artificial induction of the SR in N. gonorrhoeae by serine hydroxamate is prevented by thiostrepton, a thiopeptide antibiotic that is known to interact with ribosomal protein L11, thereby inhibiting functions of EF-Tu and EF-G, and binding of pppGpp synthase I (RelA) to ribosome upon entry of uncharged tRNA. We found that N. gonorrhoeae is highly sensitive to thiostrepton under in vitro conditions, and that thiostrepton, in contrast to other antibiotics, does not induce tolerance or persistence. Finally, we observed that thiostrepton attenuated the expression of key genes involved in the host-pathogen interaction. These properties make thiostrepton a good drug candidate for dampening bacterial virulence and preventing antibiotic tolerance and persistence. The ongoing challenge is to increase the bioavailability of thiostrepton through the use of chemistry and nanotechnology.
  • Bacillus velezensis MT9 and Pseudomonas chlororaphis MT5 as biocontrol agents against citrus sooty mold and associated insect pests
    Matteo Calcagnile, Maurizio Salvatore Tredici, Antonio Pennetta, Silvia Caterina Resta, Adelfia Talà, Giuseppe Egidio De Benedetto, Pietro Alifano
    Biological Control, 2022
  • HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis
    Adelfia Talà, Flora Guerra, Matteo Calcagnile, Roberta Romano, Silvia Caterina Resta, Aurora Paiano, Mario Chiariello, Graziano Pizzolante, Cecilia Bucci, Pietro Alifano
    Journal of Biomedical Science, 2022
    Background In Neisseria meningitidis the HrpA/HrpB two-partner secretion system (TPS) was implicated in diverse functions including meningococcal competition, biofilm formation, adherence to epithelial cells, intracellular survival and vacuolar escape. These diverse functions could be attributed to distinct domains of secreted HrpA. Methods A yeast two-hybrid screening, in vitro pull-down assay and immunofluorescence microscopy experiments were used to investigate the interaction between HrpA and the dynein light-chain, Tctex-type 1 (DYNLT1). In silico modeling was used to analyze HrpA structure. Western blot analysis was used to investigate apoptotic and pyroptotic markers. Results The HrpA carboxy-terminal region acts as a manganese-dependent cell lysin, while the results of a yeast two-hybrid screening demonstrated that the HrpA middle region has the ability to bind the dynein light-chain, Tctex-type 1 (DYNLT1). This interaction was confirmed by in vitro pull-down assay and immunofluorescence microscopy experiments showing co-localization of N. meningitidis with DYNLT1 in infected epithelial cells. In silico modeling revealed that the HrpA-M interface interacting with the DYNLT1 has similarity with capsid proteins of neurotropic viruses that interact with the DYNLT1. Indeed, we found that HrpA plays a key role in infection of and meningococcal trafficking within neuronal cells, and is implicated in the modulation of the balance between apoptosis and pyroptosis. Conclusions Our findings revealed that N. meningitidis is able to effectively infect and survive in neuronal cells, and that this ability is dependent on HrpA, which establishes a direct protein–protein interaction with DYNLTI in these cells, suggesting that the HrpA interaction with dynein could be fundamental for N. meningitidis spreading inside the neurons. Moreover, we found that the balance between apoptotic and pyroptotic pathways is heavily affected by HrpA.
  • Phenotyping of Fecal Microbiota of Winnie, a Rodent Model of Spontaneous Chronic Colitis, Reveals Specific Metabolic, Genotoxic, and Pro-inflammatory Properties
    Adelfia Talà, Flora Guerra, Silvia Caterina Resta, Matteo Calcagnile, Amilcare Barca, Salvatore Maurizio Tredici, Maria Dolores De Donno, Mirco Vacca, Marina Liso, Marcello Chieppa, Maria De Angelis, Tiziano Verri, Maria Giuseppina Bozzetti, Cecilia Bucci, Pietro Alifano
    Inflammation, 2022
    Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information.
  • Surface architecture of Neisseria meningitidis capsule and outer membrane as revealed by atomic force microscopy
    Daniela Erminia Manno, Adelfia Talà, Matteo Calcagnile, Silvia Caterina Resta, Pietro Alifano, Antonio Serra
    Research in Microbiology, 2021

RECENT SCHOLAR PUBLICATIONS

  • Neisseria meningitidis : a traditional extracellular pathogen with an intense intracellular lifestyle
    SC Resta, A Talà, R Conte, M Calcagnile, C Bucci, P Alifano
    Frontiers in Cellular and Infection Microbiology 15, 1733264 , 2025
    2025
    Citations: 2
  • Propionic acid toxicity and utilization of α-ketobutyric acid in Neisseria meningitidis via the methylcitrate cycle under specific conditions
    A Talà, M Calcagnile, SC Resta, SM Tredici, GE De Benedetto, C Bucci, ...
    Microbiology Spectrum 13 (12), e00783-25 , 2025
    2025
    Citations: 3
  • Effects of surface-exposed sialic acid and LOS outer core on the ability of native Neisseria meningitidis outer membrane vesicles (nOMVs) to induce cytokine …
    SC Resta, A Talà, A Baccante, G Saudino, P Petruccelli, V Di Cioccio, ...
    Scientific Reports , 2025
    2025
  • Beyond inflammation: Role of pyroptosis pathway activation by gram-negative bacteria and their outer membrane vesicles (OMVs) in the interaction with the host cell
    SC Resta, F Guerra, A Talà, C Bucci, P Alifano
    Cells 13 (21), 1758 , 2024
    2024
    Citations: 13
  • Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system
    C Pagliuca, R Colicchio, SC Resta, A Talà, E Scaglione, G Mantova, ...
    Frontiers in Cellular and Infection Microbiology 14, 1384072 , 2024
    2024
    Citations: 5
  • Role of HrpA-Dynein interaction in meningococcal infection
    SC Resta, A Talà, F Guerra, M Calcagnile, R Romano, A Paiano, ...
    Frontiers Abstract Book , 2024
    2024
  • Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae
    A Talà, M Calcagnile, SC Resta, A Pennetta, GE De Benedetto, P Alifano
    Frontiers in Microbiology 14, 1104454 , 2023
    2023
    Citations: 8
  • Bacillus velezensis MT9 and Pseudomonas chlororaphis MT5 as biocontrol agents against citrus sooty mold and associated insect pests
    M Calcagnile, MS Tredici, A Pennetta, SC Resta, A Talà, ...
    Biological Control 176, 105091 , 2022
    2022
    Citations: 23
  • HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis
    A Talà, F Guerra, M Calcagnile, R Romano, SC Resta, A Paiano, ...
    Journal of Biomedical Science 29 (1), 45 , 2022
    2022
    Citations: 13
  • Phenotyping of fecal microbiota of Winnie, a rodent model of spontaneous chronic colitis, reveals specific metabolic, genotoxic, and pro-inflammatory properties
    A Talà, F Guerra, SC Resta, M Calcagnile, A Barca, SM Tredici, ...
    Inflammation 45 (6), 2477 , 2022
    2022
    Citations: 10
  • Surface architecture of Neisseria meningitidis capsule and outer membrane as revealed by atomic force microscopy
    DE Manno, A Talà, M Calcagnile, SC Resta, P Alifano, A Serra
    Research in microbiology 172 (6), 103865 , 2021
    2021
    Citations: 4

MOST CITED SCHOLAR PUBLICATIONS

  • Bacillus velezensis MT9 and Pseudomonas chlororaphis MT5 as biocontrol agents against citrus sooty mold and associated insect pests
    M Calcagnile, MS Tredici, A Pennetta, SC Resta, A Talà, ...
    Biological Control 176, 105091 , 2022
    2022
    Citations: 23
  • Beyond inflammation: Role of pyroptosis pathway activation by gram-negative bacteria and their outer membrane vesicles (OMVs) in the interaction with the host cell
    SC Resta, F Guerra, A Talà, C Bucci, P Alifano
    Cells 13 (21), 1758 , 2024
    2024
    Citations: 13
  • HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis
    A Talà, F Guerra, M Calcagnile, R Romano, SC Resta, A Paiano, ...
    Journal of Biomedical Science 29 (1), 45 , 2022
    2022
    Citations: 13
  • Phenotyping of fecal microbiota of Winnie, a rodent model of spontaneous chronic colitis, reveals specific metabolic, genotoxic, and pro-inflammatory properties
    A Talà, F Guerra, SC Resta, M Calcagnile, A Barca, SM Tredici, ...
    Inflammation 45 (6), 2477 , 2022
    2022
    Citations: 10
  • Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae
    A Talà, M Calcagnile, SC Resta, A Pennetta, GE De Benedetto, P Alifano
    Frontiers in Microbiology 14, 1104454 , 2023
    2023
    Citations: 8
  • Neisseria meningitidis activates pyroptotic pathways in a mouse model of meningitis: role of a two-partner secretion system
    C Pagliuca, R Colicchio, SC Resta, A Talà, E Scaglione, G Mantova, ...
    Frontiers in Cellular and Infection Microbiology 14, 1384072 , 2024
    2024
    Citations: 5
  • Surface architecture of Neisseria meningitidis capsule and outer membrane as revealed by atomic force microscopy
    DE Manno, A Talà, M Calcagnile, SC Resta, P Alifano, A Serra
    Research in microbiology 172 (6), 103865 , 2021
    2021
    Citations: 4
  • Propionic acid toxicity and utilization of α-ketobutyric acid in Neisseria meningitidis via the methylcitrate cycle under specific conditions
    A Talà, M Calcagnile, SC Resta, SM Tredici, GE De Benedetto, C Bucci, ...
    Microbiology Spectrum 13 (12), e00783-25 , 2025
    2025
    Citations: 3
  • Neisseria meningitidis : a traditional extracellular pathogen with an intense intracellular lifestyle
    SC Resta, A Talà, R Conte, M Calcagnile, C Bucci, P Alifano
    Frontiers in Cellular and Infection Microbiology 15, 1733264 , 2025
    2025
    Citations: 2
  • Effects of surface-exposed sialic acid and LOS outer core on the ability of native Neisseria meningitidis outer membrane vesicles (nOMVs) to induce cytokine …
    SC Resta, A Talà, A Baccante, G Saudino, P Petruccelli, V Di Cioccio, ...
    Scientific Reports , 2025
    2025
  • Role of HrpA-Dynein interaction in meningococcal infection
    SC Resta, A Talà, F Guerra, M Calcagnile, R Romano, A Paiano, ...
    Frontiers Abstract Book , 2024
    2024