Francesco Messina
@inmi.it
Scopus Publications
- High-Resolution Genomic Surveillance of Carbapenem-Resistant Acinetobacter baumannii: IC-2 Clonal Diversity, Resistance Determinants, and Virulence Signatures
Arianna Basile, Valentina Antonelli, Claudia Rotondo, Michele Properzi, Francesco Messina, et al.
Antibiotics, 2026
Background/Objectives: Acinetobacter baumannii is a critical opportunistic pathogen causing severe healthcare-associated infections, particularly in intensive care units. The global dissemination of carbapenem-resistant A. baumannii (CRAB) and its environmental persistence necessitate continuous genomic surveillance to monitor high-risk clones. Methods: We conducted whole-genome sequencing (WGS), core genome multi-locus sequence typing (cgMLST), and phylogenomic analyses on 26 CRAB isolates collected at the National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” IRCCS (September 2023–September 2024). Antimicrobial resistance determinants, virulence-related genes, and capsular (KL) and lipooligosaccharide outer core (OCL) loci were characterized by interrogation of comprehensive bioinformatic pipelines. Results: All CRAB isolates displayed an extensively drug-resistant (XDR) phenotype, with a shared resistance pattern to carbapenems, aminoglycosides, fluoroquinolones, fosfomycin, and sulfonamides, while being susceptible only to colistin and cefiderocol. The carbapenemase gene blaOXA-23 was detected in all CRAB isolates, together with clone-specific blaOXA-51-like variants. For all isolates, the resistome profile fully matched the observed resistance phenotype. All isolates belonged to the International Clonal Lineage II (ICL II), Pasteur Sequence Type (ST) 2, and Oxford ST369, ST208, and ST455. Integration of cgMLST data with phylogenomic analyses and genome-based classification of KL and OCL loci revealed five distinct clusters, each one including nearly identical isolates, indicating both intra-hospital dissemination and possible inter-hospital transmission. Virulome profiling revealed heterogeneous repertoires of virulence-associated genes, resulting in cluster-specific patterns, while patristic analysis identified phylogenetic clusters linking the study isolates to other Italian and other European lineages. Conclusions: This study underscores the complex genomic landscape of CRAB in our setting, driven by the circulation of different ICL II clonal types, and reinforces the urgency of integrated genomic surveillance and robust antimicrobial stewardship to mitigate the spread of high-risk XDR A. baumannii clones. - Comprehensive Whole Genome Sequencing Dataset of Mycobacterium tuberculosis Strains Collected Across Italy
Arash Ghodousi, Angela Cannas, Elisa Tagliani, Virginia Batignani, Francesco Bisognin, et al.
Scientific Data, 2025 - Investigating Skin Microbial Community in Malignant Melanoma Lesions
Michele Properzi, Valentina Dimartino, Daniele Pietrucci, Carla Fontana, Claudia Rotondo, et al.
Microorganisms, 2025
The skin microbiome is identified as one of the crucial factors in several pathological conditions, including its potential capacity in modulating cancer progression and response to treatment. A strong association of Bacilli and Betaproteobacteria classes and the Bacteroidetes phylum with melanoma is described in patients with cutaneous malignancies, while an imbalance of S. epidermidis and S. aureus is related to the progression of other skin cancers. In the present study, we characterized the microbial community in suspected lesions of 35 patients, classified, after histological analysis, as malignant melanoma lesions and benign non-melanoma lesions. Mirrored healthy skin were also included as negative control. No significant difference in alpha and beta diversity was observed when samples were categorized in four different groups (melanoma samples vs. contralateral healthy samples; melanoma samples vs. benign lesions; benign lesions vs. contralateral controls; melanoma controls vs. benign controls). The differential abundance analyses show that Corynebacterium urealyticum is more abundant in melanoma samples compared to their control, while Roseomonas gilardii is less abundant in melanoma. Staphylococcus massiliensis, Bacillus coagulans, Paracoccus yeei, Corynebacterium jeikeium, and Corynebacterium pyruviciproducens are present only in melanoma samples when compared with benign lesions. - Molecular exploration of host-pathogen interactions in severe Pseudomonas aeruginosa infection through a multi-level data integration approach
Francesco Messina, Claudia Rotondo, Luiz Ladeira, Sara Crosetti, Michele Properzi, et al.
Frontiers in Medicine, 2025
IntroductionUnderstanding host-pathogen interactions is crucial for explaining the variability in sepsis outcomes, with Pseudomonas aeruginosa (PA) remaining a significant public health concern. In this work, we explored PA-human host interaction mechanisms through a data integration workflow, focusing on protein-protein and metabolite-protein interactions, along with pathway modulation in affected organs during severe infections.MethodsA scoping literature review enabled us to construct a domain-based infection network encompassing pathogenesis concepts, molecular interactions, and host response signatures, providing a wide view of the relevant mechanisms involved in severe bacterial infections.ResultsOur analysis yielded a literature-based comprehensive description of PA infection mechanisms and an annotated dataset of 189 PA-human interactions involving 151 proteins/molecules (109 human proteins, 3 human metabolites, 34 PA proteins, and 5 PA molecules). This dataset was complemented with gene expression analysis from in vivo PA-infected lung samples. The results indicated a notable overexpression of proinflammatory pathways and PA-mediated modulation of host lung responses.DiscussionOur comprehensive molecular network of PA infection represents a valuable tool for the understanding of severe bacterial infections and offers potential applications in predicting clinical phenotypes. Through this approach combining omics data, clinical information, and pathogen characteristics, we have provided a foundation for future research in host-pathogen interactions and the mechanistic grounds to build dynamic computational models for clinical phenotype predictions. - Vδ2 T-cells response in people with Mpox infection: a three-month longitudinal assessment
Eleonora Cimini, Eleonora Tartaglia, Francesco Messina, Andrea Coppola, Valentina Mazzotta, et al.
Emerging Microbes and Infections, 2025
The first evidence that Orthopoxvirus induced the expansion in vivo and the recall of effector innate Vδ2 T-cells was described in a macaque model. Although, an engagement of αβ T-cells specific response in patients infected with human monkeypox (Mpox) was demonstrated, little is known about the role of γδ T-cells during Mpox infection. IFN-γ-producing γδ T-cells in the resistance to poxviruses may a key role in inducing a protective type 1 memory immunity. We analyzed the kinetics of Vδ2 T-cell response from the acute phase up to three months after Mpox infection. Fourteen MSM subjects (5 PWH, 35.7%) were enrolled in a longitudinal study from May to July 2022. Blood samples were collected in the early phase of infection (T1, T2) and at 3 months (T3M) post-symptom onset. Vδ2 T-cell profiles (CD45RA/CCR7), activation/exhaustion markers (CD38/HLA-DR/CD57/PD-1/TIM-3), cytokine production (IFN-γ/TNF-α) and CD107a expression were assessed by multiparametric flow cytometry. Ten healthy donors (HD) were used as a control group. At T1, Vδ2 T-cell frequency of patients decreased, and effector memory Vδ2 T-cells increased with respect to HD. Activation/exhaustion markers were higher than HD. Vδ2 functionality decreased at T1 related to HD, and it was associated with CD38 and HLA-DR higher expression as well as TIM-3. Vδ2 T-cells restored their profile at T3M. The presence of effector/activated Vδ2 T-cells in the early stages of Mpox infection and their capability to activate quickly, producing pro-inflammatory cytokines, may be useful to enhance the early adaptive response to human Mpox, maintaining a protective memory/effector T-cell response. - Immune digital twins for complex human pathologies: applications, limitations, and challenges
Anna Niarakis, Reinhard Laubenbacher, Gary An, Yaron Ilan, Jasmin Fisher, et al.
Npj Systems Biology and Applications, 2024
Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as “proof of concept” regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality. - Molecular Characterization of Multidrug-Resistant and Hypervirulent New Delhi Metallo-Beta-Lactamase Klebsiella pneumoniae in Lazio, Italy: A Five-Year Retrospective Study
Claudia Rotondo, Carolina Venditti, Ornella Butera, Valentina Dimartino, Francesco Messina, et al.
Antibiotics, 2024
Background/Objectives: Antimicrobial resistance represents a challenge to public health systems because of the array of resistance and virulence mechanisms that lead to treatment failure and increased mortality rates. Although for years the main driver of carbapenem resistance in Italy has been the Klebsiella pneumoniae KPC carbapenemase, recent years have seen an increase in VIM and NDM metallo-beta-lactamases (MBLs). We conducted a five-year survey of New Delhi Metallo-beta-Lactamase (NDM)-producing Klebsiella pneumoniae (NDM-Kpn) clinical isolates from the Lazio region, Italy; the study aimed to elucidate the molecular mechanisms underpinning their resistant and virulent phenotype. Methods: Antimicrobial susceptibility was evaluated by automated systems and broth microdilution. In silico analysis of acquired resistance and virulence genes was performed using whole-genome sequencing (WGS), molecular typing through MLST, and core genome multi-locus sequence typing (cgMLST). Conclusions: A total of 126 clinical NDM-Kpn isolates were collected from 19 distinct hospitals in the Lazio region. Molecular analysis highlighted the existence of NDM-1 (108/126) and NDM-5 (18/126) variants, 18 Sequence Types (STs), and 15 Cluster Types (CTs). Notably, 31/126 isolates displayed a virulence score of 4, carrying ybt, ICEKp, iuc, and rmp genes. This study identified a variety of NDM-Kpn STs, mainly carrying the blaNDM-1 gene, with a significant number linked to high-risk clones. Of these isolates, 24.6% showed high-level resistance and virulence, emphasizing the risk of the spread of strains that combine multi-drug-resistance (MDR) and virulence. Proactive surveillance and international collaborations are needed to prevent the spread of high-risk clones, as well as further research into new antimicrobial agents to fight antibiotic resistance. - Cerebrospinal Fluid and Peripheral Blood Lymphomonocyte Single-Cell Transcriptomics in a Subject with Multiple Sclerosis Acutely Infected with HIV
Carmela Pinnetti, Gabriella Rozera, Francesco Messina, Pietro Giorgio Spezia, Elisabetta Lazzari, et al.
International Journal of Molecular Sciences, 2024
Signatures of neurodegeneration in clinical samples from a subject with multiple sclerosis (MS) acutely infected with HIV were investigated with single-cell transcriptomics using 10X Chromium technology. Sequencing was carried out on NovaSeq-TM, and the analysis was performed with Cell Ranger software (v 7.1.0) associated with a specifically established bioinformatic pipeline. A total of 1446 single-cell transcriptomes in cerebrospinal fluid (CSF) and 4647 in peripheral blood mononuclear cells (PBMCs) were obtained. In the CSF, many T-cell lymphocytes with an enriched amount of plasma cells and plasmacytoid dendritic (pDC) cells, as compared to the PBMCs, were detected. An unsupervised cluster analysis, putting together our patient transcriptomes with those of a publicly available MS scRNA-seq dataset, showed up-regulated microglial neurodegenerative gene expression in four clusters, two of which included our subject’s transcriptomes. A few HIV-1 transcripts were found only in the CD4 central memory T-cells of the CSF compartment, mapping to the gag-pol, vpu, and env regions. Our data, which describe the signs of neurodegenerative gene expression in a very peculiar clinical situation, did not distinguish the cause between multiple sclerosis and HIV infection, but they can give a glimpse of the high degree of resolution that may be obtained by the single-cell transcriptomic approach. - Sanitary Waters: Is It Worth Looking for Mycobacteria?
Angela Cannas, Francesco Messina, Paola Dal Monte, Francesco Bisognin, Giorgio Dirani, et al.
Microorganisms, 2024
The freshwater environment is suitable for nontuberculous mycobacteria (NTMs) growth. Their high adaptability represents a considerable risk for sanitary water systems, which are a potential vector for NTMs transmission. This study investigated the occurrence of NTMs, such as Mycobacterium saskatchewanense, in hospital water systems to support the surveillance and control of potentially pathogenic NTMs. We analyzed 722 ultrapure dialysis fluid samples from Emilia Romagna Dialysis Services. Among these, 35 samples were found to be positive for M. saskatchewanense. The strains were characterized using whole-genome sequencing (WGS) and variability analysis was carried out along the whole M. saskatchewanense genome. This investigation revealed the exclusive presence of M. saskatchewanense in these dialysis machines, with low genetic variability among all strains (with a low number of different alleles: <15). The strong similarity among the strain groups was also confirmed in the WGS-based ML tree, with very few significant nodes, and no clusters were identified. This research highlights the necessity of implementing surveillance protocols and investigating any potential link to human infections, as well as stressing the urgency of enhancing surveillance and infection control measures. - Screening of Klebsiella pneumoniae subsp. pneumoniae Strains with Multi-Drug Resistance and Virulence Profiles Isolated from an Italian Hospital between 2020 and 2023
Valentina Dimartino, Carolina Venditti, Francesco Messina, Silvia D’Arezzo, Marina Selleri, et al.
Antibiotics, 2024
Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020–2023). A genome-based surveillance of all MDR CRE-K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital. - Implementation of Whole Genome Sequencing of Tuberculosis Isolates in a Referral Center in Rome: Six Years’ Experience in Characterizing Drug-Resistant TB and Disease Transmission
Angela Cannas, Ornella Butera, Antonio Mazzarelli, Francesco Messina, Antonella Vulcano, et al.
Antibiotics, 2024 - Epidemiological and Molecular Investigation of the Heater–Cooler Unit (HCU)-Related Outbreak of Invasive Mycobacterium chimaera Infection Occurred in Italy
Angela Cannas, Antonella Campanale, Daniela Minella, Francesco Messina, Ornella Butera, et al.
Microorganisms, 2023 - Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches
Anna Niarakis, Marek Ostaszewski, Alexander Mazein, Inna Kuperstein, Martina Kutmon, et al.
Frontiers in Immunology, 2023 - Detection of recombinant breakpoint in the genome of human enterovirus E11 strain associated with a fatal nosocomial outbreak
Martina Rueca, Simone Lanini, Emanuela Giombini, Francesco Messina, Concetta Castilletti, et al.
Virology Journal, 2022 - Investigating the Origin of Mycobacterium chimaera Contamination in Heater-Cooler Units: Integrated Analysis with Fourier Transform Infrared Spectroscopy and Whole-Genome Sequencing
F. Bisognin, F. Messina, O. Butera, C. Nisii, A. Mazzarelli, et al.
Microbiology Spectrum, 2022 - Machine Learning Data Analysis Highlights the Role of Parasutterella and Alloprevotella in Autism Spectrum Disorders
Daniele Pietrucci, Adelaide Teofani, Marco Milanesi, Bruno Fosso, Lorenza Putignani, et al.
Biomedicines, 2022 - Very High Negative Concordance Rate of RT-PCR for SARS-CoV-2 in Nasopharyngeal Swab and Tracheo-Bronchial Aspirate in Children
Anna Camporesi, Annalisa De Silvestri, Veronica Diotto, Stefania Ferrario, Laura Eccher, et al.
Frontiers in Pediatrics, 2022 - Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021
Francesca Colavita, Silvia Meschi, Cesare Ernesto Maria Gruber, Martina Rueca, Francesco Vairo, et al.
Frontiers in Medicine, 2022 - The Easy-to-Use SARS-CoV-2 Assembler for Genome Sequencing: Development Study
Martina Rueca, Emanuela Giombini, Francesco Messina, Barbara Bartolini, Antonino Di Caro, et al.
Jmir Bioinformatics and Biotechnology, 2022 - Multi-omics approach to COVID-19: a domain-based literature review
Chiara Montaldo, Francesco Messina, Isabella Abbate, Manuela Antonioli, Veronica Bordoni, et al.
Journal of Translational Medicine, 2021 - Corrigendum to: COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms (Molecular Systems Biology, (2021), 17, 10, 10.15252/msb.202110387)
Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, Robert Phair, et al.
Molecular Systems Biology, 2021 - Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia
Alessandra Vergori, Patrizia Lorenzini, Alessandro Cozzi-Lepri, Davide Roberto Donno, Gina Gualano, et al.
Scientific Reports, 2021 - COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms
Marek Ostaszewski, Anna Niarakis, Alexander Mazein, Inna Kuperstein, Robert Phair, et al.
Molecular Systems Biology, 2021 - Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2–host interactome
Francesco Messina, Emanuela Giombini, Chiara Montaldo, Ashish Arunkumar Sharma, Antonio Zoccoli, et al.
Cell Death and Disease, 2021 - Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae
Carolina Venditti, Ornella Butera, Marcello Meledandri, Maria Pia Balice, Giulio Cesare Cocciolillo, et al.
Clinical Microbiology and Infection, 2021
