Immunology, Transplantation and Infectious diseases

Emerging bacterial pathogens

Group leader

Daniela Maria Cirillo

CSQ-IQNet_EN

The unit is engaged in the following areas:

research activities in the field of mycobacteria and nosocomial pathogens,
accredited specialized diagnostics for mycobacterial infections,
molecular epidemiology and typing of nosocomial pathogens for the OSR infection control committee,
international public health activities in the TB field,
international trainings in the field of mycobacterial diseases and multidrug resistant pathogens.

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Research activity

The main research focus is on tuberculosis and other mycobacterial diseases with multiple lines of research:

Investigation of the determinants of drug resistance at genomic level and the correlation between specific SNPs in relevant genes and an increase in the phenotypic resistance by quantitative methods.
Investigation of the pathogen’s associated determinants leading to the progression of the disease with a focus on the role of non-coding genomic regions.
Design and evaluation of new diagnostic assays.
Investigation of TB transmission dynamics among vulnerable population and the best strategy to be implemented for an early detection.
Use of whole genome sequencing (WGS) and in-house bioinformatic pipelines for the surveillance of TB outbreaks.
WGS-based revision of the taxonomy of NTMs and transmission investigation.
Development of a mouse model of lung chronic infection to study disease progression after NTMs infection and response to novel antibiotic therapies.

In addition, the group focus on virulence factors responsible for antimicrobial drug resistance in nosocomial pathogens. The unit identified virulence factors promoting the successful establishment of selected methicillin resistant S.aureus and KPC producing K.pneumoniae clones in hospitals. Moreover, researchers recently implemented WGS and customized bioinformatics pipelines as a tool to investigate transmission and virulence factors of multidrug resistant pathogens at both nosocomial and community level.

Selected publications

Quaresima V, Naldini MM, Cirillo DM. The prospects for the SARS-CoV-2 pandemic in Africa EMBO Mol Med. 2020 Apr 16. doi: 10.15252/emmm.202012488.

Gona F, Comandatore F, Battaglia S, Piazza A, Trovato A, Lorenzin G, Cichero P, Biancardi A, Nizzero P, Moro M, Cirillo DM. Comparison of core-genome MLST, coreSNP and PFGE methods for Klebsiella pneumoniae cluster analysis. Microb Genom. 2020 Mar 9. ISSN: 2057-5858, doi: 10.1099/mgen.0.000347.

Dean AS, Zignol M, Cabibbe AM, Falzon D, Glaziou P, Cirillo DM, Köser CU, Gonzalez-Angulo LY, Tosas-Auget O, Ismail N, Tahseen S, Ama MCG, Skrahina A, Alikhanova N, Kamal SMM, Floyd K. Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data. PLoS Med. 2020 Jan 21;17(1):e1003008. ISSN: 1932-6203, doi: 10.1371/journal.pmed.1003008. eCollection 2020 Jan.

Jajou R, Kohl TA, Walker T, Norman A, Cirillo DM, Tagliani E, Niemann S, de Neeling A, Lillebaek T, Anthony RM, van Soolingen D. Towards standardisation: comparison of five whole genome sequencing (WGS) analysis pipelines for detection of epidemiologically linked tuberculosis cases. Euro Surveill. 2019 Dec;24(50). ISSN: 1560-7917, doi: 10.2807/1560-7917.ES.2019.24.50.1900130.

Temesgen Z, Cirillo DM, Raviglione MC. Precision medicine and public health interventions: tuberculosis as a model? Lancet Public Health. 2019 Aug;4(8):e374. ISSN 2468-2667, doi: 10.1016/S2468-2667(19)30130-6.

Tortoli E, Brown-Elliott BA, Chalmers JD, Cirillo DM, Daley CL, Emler S, Floto RA, Garcia MJ, Hoefsloot W, Koh WJ, Lange C, Loebinger M, Maurer FP, Morimoto K, Niemann S, Richter E, Turenne CY, Vasireddy R, Vasireddy S, Wagner D, Wallace RJ Jr, Wengenack N, van Ingen J. Same meat, different gravy: ignore the new names of mycobacteria. Eur Respir J. 2019 Jul 11;54(1). pii: 1900795. ISSN: 0903-1936, doi: 10.1183/13993003.00795-2019.

Ghodousi A, Rizvi AH, Baloch AQ, Ghafoor A, Khanzada FM, Qadir M, Borroni E, Trovato A, Tahseen S, Cirillo DM. Acquisition of cross-resistance to Bedaquiline and Clofazimine following treatment for Tuberculosis in Pakistan. Antimicrob Agents Chemother. 2019 Jul 1. pii: AAC.00915-19. ISSN‎: ‎0066-4804, doi: 10.1128/AAC.00915-19.

Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, Farhat MR, Guthrie JL, Laukens K, Miotto P, Ofori-Anyinam B, Dreyer V, Supply P, Suresh A, Utpatel C, van Soolingen D, Zhou Y, Ashton PM, Brites D, Cabibbe AM, de Jong BC, de Vos M, Menardo F, Gagneux S, Gao Q, Heupink TH, Liu Q, Loiseau C, Rigouts L, Rodwell TC, Tagliani E, Walker TM, Warren RM, Zhao Y, Zignol M, Schito M, Gardy J, Cirillo DM, Niemann S, Comas I, Van Rie A. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nat Rev Microbiol. 2019 Jun 17. doi: 10.1038/s41579-019-0214-5.

Ghodousi A, Tagliani E, Karunaratne E, Niemann S, Perera J, Köser CU, Cirillo DM. Isoniazid Resistance in Mycobacterium tuberculosis Is a Heterogeneous Phenotype Composed of Overlapping MIC Distributions with Different Underlying Resistance Mechanisms. Antimicrob Agents Chemother. 2019 Jun 24;63(7). pii: e00092-19. ISSN‎: ‎0066-4804,doi: 10.1128/AAC.00092-19.

Nikolayevskyy V, Niemann S, Anthony R, van Soolingen D, Tagliani E, Ködmön C, van der Werf MJ, Cirillo DM. Role and value of whole genome sequencing in studying tuberculosis transmission. Clin Microbiol Infect. 2019 Apr 11. pii: S1198-743X(19)30124-7. ISSN: 1198-743X, doi: 10.1016/j.cmi.2019.03.022. Review.

Tornheim JA, Starks AM, Rodwell TC, Gardy JL, Walker TM, Cirillo DM, Jayashankar L, Miotto P, Zignol M, Schito M. Building the framework for standardized clinical laboratory reporting of next generation sequencing data for resistance-associated mutations in Mycobacterium tuberculosis complex. Clin Infect Dis. 2019 Mar 18. pii: ciz219. ISSN: 1058-4838, doi: 10.1093/cid/ciz219.

Bouzouita I, Cabibbe AM, Trovato A, Daroui H, Ghariani A, Midouni B, Essalah L, Mehiri E, Cirillo DM, Saidi LS. Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012-2016. Emerg Infect Dis. 2019 Mar;25(3):538-546. ISSN: 1080-6040, doi: 10.3201/eid2503.181370.

El Achkar S, Demanche C, Osman M, Rafei R, Ismail MB, Yaacoub H, Pinçon C, Duthoy S, De Matos F, Gaudin C, Trovato A, Cirillo DM, Hamze M, Supply P. Drug-Resistant Tuberculosis, Lebanon, 2016 - 2017. Emerg Infect Dis. 2019 Mar;25(3):564-568. ISSN: 1080-6040, doi: 10.3201/eid2503.181375.

CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I, Bi L, Beckert P, Bonnet M, Bradley P, Cabibbe AM, Cancino-Muñoz I, Caulfield MJ, Chaiprasert A, Cirillo DM, Clifton DA, Comas I, Crook DW, De Filippo MR, de Neeling H, Diel R, Drobniewski FA, Faksri K, Farhat MR, Fleming J, Fowler P, Fowler TA, Gao Q, Gardy J, Gascoyne-Binzi D, Gibertoni-Cruz AL, Gil-Brusola A, Golubchik T, Gonzalo X, Grandjean L, He G, Guthrie JL, Hoosdally S, Hunt M, Iqbal Z, Ismail N, Johnston J, Khanzada FM, Khor CC, Kohl TA, Kong C, Lipworth S, Liu Q, Maphalala G, Martinez E, Mathys V, Merker M, Miotto P, Mistry N, Moore DAJ, Murray M, Niemann S, Omar SV, Ong RT, Peto TEA, Posey JE, Prammananan T, Pym A, Rodrigues C, Rodrigues M, Rodwell T, Rossolini GM, Sánchez Padilla E, Schito M, Shen X, Shendure J, Sintchenko V, Sloutsky A, Smith EG, Snyder M, Soetaert K, Starks AM, Supply P, Suriyapol P, Tahseen S, Tang P, Teo YY, Thuong TNT, Thwaites G, Tortoli E, van Soolingen D, Walker AS, Walker TM, Wilcox M, Wilson DJ, Wyllie D, Yang Y, Zhang H, Zhao Y, Zhu B. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med. 2018 Oct 11;379(15):1403-1415. doi: 10.1056/NEJMoa1800474. Epub 2018 Sep 26.