Christophe Sola
@universite-paris-saclay.fr
Life Sciences Department/Faculty of Sciences/Universite-Paris-Saclay
Christophe Sola holds since September 2007 a Full Professorship position in Microbiology at University of Paris-Saclay (UPSay) where he was the Principal Investigator of his research team IGEPE between 2007 and 2019. He is now a senior scientist in an INSERM-University-Paris -Cité Joint Research Unit, named IAME, that stands for “Infection, Antimicrobials, Modeling and Evolution”, working in a lab associated to the French National Research Center Laboratory for Mycobacetriology. His research work focus on Mycobacterium tuberculosis genetic diversity and especially on CRISPR polymorphisms. He was at the origin of the International Spoligotyping Databases created and maintained at the Institut Pasteur, databases that were instrumental in helping to decipher the population structure of the Mycobacterium tuberculosis complex before the Whole-Genome-Sequence era. He is now working in Big Dataset management systems, by developing and analyzing data for public health and academic research
EDUCATION
PharmD PhD
RESEARCH, TEACHING, or OTHER INTERESTS
Microbiology, Applied Microbiology and Biotechnology, Infectious Diseases, Ecology, Evolution, Behavior and Systematics
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Christophe Guyeux, Gaetan Senelle, Adrien Le Meur, Philip Supply, Cyril Gaudin, Jody E. Phelan, Taane G Clark, Leen Rigouts, Bouke de Jong, Christophe Sola,et al.
Centers for Disease Control and Prevention (CDC)
Analysis of genome sequencing data from >100,000 genomes of Mycobacterium tuberculosis complex using TB-Annotator software revealed a previously unknown lineage, proposed name L10, in central Africa. Phylogenetic reconstruction suggests L10 could represent a missing link in the evolutionary and geographic migration histories of M. africanum.
Gaetan Senelle, Muhammed Rabiu Sahal, Kevin La, Typhaine Billard-Pomares, Julie Marin, Faiza Mougari, Antoine Bridier-Nahmias, Etienne Carbonnelle, Emmanuelle Cambau, Guislaine Refrégier,et al.
Elsevier BV
György Pálfi, Olivier Dutour, Tamás Hajdu, Christophe Sola, and Albert Zink
Elsevier BV
R. Zein-Eddine, F. Hak, A. Le Meur, C. Genestet, O. Dumitrescu, C. Guyeux, G. Senelle, C. Sola, and G. Refrégier
Elsevier BV
Gaetan Senelle, Christophe Guyeux, Guislaine Refrégier, and Christophe Sola
Elsevier BV
Gary Napier, David Couvin, Guislaine Refrégier, Christophe Guyeux, Conor J. Meehan, Christophe Sola, Susana Campino, Jody Phelan, and Taane G. Clark
Springer Science and Business Media LLC
AbstractBacterial strain-types in the Mycobacterium tuberculosis complex underlie tuberculosis disease, and have been associated with drug resistance, transmissibility, virulence, and host–pathogen interactions. Spoligotyping was developed as a molecular genotyping technique used to determine strain-types, though recent advances in whole genome sequencing (WGS) technology have led to their characterization using SNP-based sub-lineage nomenclature. Notwithstanding, spoligotyping remains an important tool and there is a need to study the congruence between spoligotyping-based and SNP-based sub-lineage assignation. To achieve this, an in silico spoligotype prediction method (“Spolpred2”) was developed and integrated into TB-Profiler. Lineage and spoligotype predictions were generated for > 28 k isolates and the overlap between strain-types was characterized. Major spoligotype families detected were Beijing (25.6%), T (18.6%), LAM (13.1%), CAS (9.4%), and EAI (8.3%), and these broadly followed known geographic distributions. Most spoligotypes were perfectly correlated with the main MTBC lineages (L1-L7, plus animal). Conversely, at lower levels of the sub-lineage system, the relationship breaks down, with only 65% of spoligotypes being perfectly associated with a sub-lineage at the second or subsequent levels of the hierarchy. Our work supports the use of spoligotyping (membrane or WGS-based) for low-resolution surveillance, and WGS or SNP-based systems for higher-resolution studies.
Muhammed Rabiu Sahal, Gaetan Senelle, Kevin La, Tukur Wada Panda, Dalha Wada Taura, Christophe Guyeux, Emmanuelle Cambau, and Christophe Sola
Public Library of Science (PLoS)
In this article, we provide an in-depth analysis on the drug-resistance phenotypic characteristics of a cohort of 325 tuberculosis and characterize by Whole Genome Sequencing 24 isolates from Nigeria belonging to L4, L5 and L6. Our results suggest an alarming rate of drug-resistance of the L4.6.2.2 Mycobacterium tuberculosis complex (MTBC) lineage and a high diversity of L5. We compiled these new Sequence Read Archives (SRAs) to previously published ones from available Bioprojects run in Nigeria. We performed RAxML phylogenetic reconstructions of larger samples that include public NCBI SRAs from some neighboring countries (Cameroon, Ghana). To confront phylogenetic reconstruction to metadata, we used a new proprietary database named TB-Annotator. We show that L5 genomes in Northern Nigeria belong to new clades as the ones described until now and allow an update of the taxonomy of L5. In addition, we describe the L4.6.2.2 lineage in Nigeria, Cameroon and Ghana. We provide computations on the likely divergence time of L4.6.2.2 and suggest a new hypothesis concerning its origin. Finally we provide a short overview on M. bovis diversity in Nigeria. This study constitutes a baseline knowledge on the global genomic diversity, phylogeography and phylodynamics of MTBC in Nigeria, as well as on the natural history of this largely ignored but densely populated country of Africa. These results highlight the need of sequencing additional MTBC genomes in Nigeria and more generally in West-Africa, both for public health and for academic reasons. The likelihood of replacement of L5-L6 by L4.6.2.2 isolates, leave potentially little time to gather historical knowledge informative on the ancient history of tuberculosis in West-Africa.
Gaetan Senelle, Christophe Guyeux, Guislaine Refrégier, and Christophe Sola
MDPI AG
The spoligotype is a graphical description of the CRISPR locus present in Mycobacterium tuberculosis, which has the particularity of having only 68 possible spacers. This spoligotype, which can be easily obtained either in vitro or in silico, allows to have a summary information of lineage or even antibiotic resistance (when known to be associated to a particular cluster) at a lower cost. The objective of this article is to show that this representation is richer than it seems, and that it is under-exploited until now. We first recall an original way to represent these spoligotypes as points in the plane, allowing to highlight possible sub-lineages, particularities in the animal strains, etc. This graphical representation shows clusters and a skeleton in the form of a graph, which led us to see these spoligotypes as vertices of an unconnected directed graph. In this paper, we therefore propose to exploit in detail the description of the variety of spoligotypes using a graph, and we show to what extent such a description can be informative.
Christophe Guyeux, Gaetan Senelle, Guislaine Refrégier, Florence Bretelle-Establet, Emmanuelle Cambau, and Christophe Sola
Cambridge University Press (CUP)
Abstract By gathering 680 publicly available Sequence Read Archives from isolates of Mycobacterium tuberculosis complex (MTBC) including 190 belonging to the lineage 2 Beijing, and using an in-house bioinformatical pipeline, the TB-Annotator, that analyses more than 50 000 characters, we describe herein a new L2 sublineage from 20 isolates found in the Tochigi province, (Japan), that we designate as asia ancestral 5 (AAnc5). These isolates harbour a number of specific criteria (42 SNPs) and their intra-cluster pairwise distance suggests historical and not epidemiological transmission. These isolates harbour a mutation in rpoC, and do not fulfil, any of the modern Beijing lineage criteria, nor any of the other ancestral Beijing lineages described so far. Asia ancestral 5 isolates do not possess mutT2 58 and ogt 12 characteristics of modern Beijing, but possess ancestral Beijing SNPs characteristics. By looking into the literature, we found a reference isolate ID381, described in Kobe and Osaka belonging to the ‘G3’ group, sharing 36 out of the 42 specific SNPs found in AAnc5. We also assessed the intermediate position of the asia ancestral 4 (AAnc4) sublineage recently described in Thailand and propose an improved classification of the L2 that now includes AAnc4 and AAnc5. By increasing the recruitment into TB-Annotator to around 3000 genomes (including 642 belonging to L2), we confirmed our results and discovered additional historical ancestral L2 branches that remain to be investigated in more detail. We also present, in addition, some anthropological and historical data from Chinese and Japan history of tuberculosis, as well as from Korea, that could support our results on L2 evolution. This study shows that the reconstruction of the early history of tuberculosis in Asia is likely to reveal complex patterns since its emergence.
Christophe Guyeux, Guislaine Refrégier, and Christophe Sola
Springer International Publishing
Christophe Guyeux, Christophe Sola, Camille Noûs, and Guislaine Refrégier
Public Library of Science (PLoS)
Mycobacterium tuberculosis complex (MTC) CRISPR locus diversity has long been studied solely investigating the presence/absence of a known set of spacers. Unveiling the genetic mechanisms of its evolution requires a more exhaustive reconstruction in a large amount of representative strains. In this article, we point out and resolve, with a new pipeline, the problem of CRISPR reconstruction based directly on short read sequences in M. tuberculosis. We first show that the process we set up, that we coin as “CRISPRbuilder-TB” (https://github.com/cguyeux/CRISPRbuilder-TB), allows an efficient reconstruction of simulated or real CRISPRs, even when including complex evolutionary steps like the insertions of mobile elements. Compared to more generalist tools, the whole process is much more precise and robust, and requires only minimal manual investigation. Second, we show that more than 1/3 of the currently complete genomes available for this complex in the public databases contain largely erroneous CRISPR loci. Third, we highlight how both the classical experimental in vitro approach and the basic in silico spoligotyping provided by existing analytic tools miss a whole diversity of this locus in MTC, by not capturing duplications, spacer and direct repeats variants, and IS6110 insertion locations. This description is extended in a second article that describes MTC-CRISPR diversity and suggests general rules for its evolution. This work opens perspectives for an in-depth exploration of M. tuberculosis CRISPR loci diversity and of mechanisms involved in its evolution and its functionality, as well as its adaptation to other CRISPR locus-harboring bacterial species.
Fabrizio Menardo, Liliana K. Rutaihwa, Michaela Zwyer, Sonia Borrell, Iñaki Comas, Emilyn Costa Conceição, Mireia Coscolla, Helen Cox, Moses Joloba, Horng-Yunn Dou,et al.
F1000 Research Ltd
Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.
Guislaine Refrégier, Christophe Sola, and Christophe Guyeux
Springer Science and Business Media LLC
AbstractBackgroundDiversity of the CRISPR locus ofMycobacterium tuberculosiscomplex has been studied since 1997 for molecular epidemiology purposes. By targeting solely the 43 spacers present in the two first sequenced genomes (H37Rv and BCG), it gave a biased idea of CRISPR diversity and ignored diversity in the neighbouringcas-genes.ResultsWe set up tailored pipelines to explore the diversity of CRISPR-cas locus in Short Reads. We analyzed data from a representative set of 198 clinical isolates as evidenced by well-characterized SNPs.We found a relatively low diversity in terms of spacers: we recovered only the 68 spacers that had been described in 2000. We found no partial or global inversions in the sequences, letting always the Direct Variant Repeats (DVR) in the same order. In contrast, we found an unexpected diversity in the form of: SNPs in spacers and in Direct Repeats, duplications of various length, and insertions at various locations of the IS6110insertion sequence, as well as blocks of DVR deletions. The diversity was in part specific to lineages. When reconstructing evolutionary steps of the locus, we found no evidence for SNP reversal. DVR deletions were linked to recombination between IS6110insertions or between Direct Repeats.ConclusionThis work definitively shows that CRISPR locus ofM. tuberculosisdid not evolve by classical CRISPR adaptation (incorporation of new spacers) since the last most recent common ancestor of virulent lineages. The evolutionary mechanisms that we discovered could be involved in bacterial adaptation but in a way that remains to be identified.
Khaldoun Masoud, George F Araj, Lina Reslan, Sukayna Fadlallah, Michel Wehbe, Lina Itani, Aline Avedissian, Ghassan Dbaibo, Antoine Saade, Guislaine Refrégier,et al.
Journal of Infection in Developing Countries
Introduction: Data about the genotypes of circulating Mycobacterium tuberculosis isolates (MTB) in Lebanon are scarce. This study was undertaken to reveal the spoligotypes of MTB isolates recovered from patients in Lebanon.
 Methodology: MTB isolates from 49 patients living in Lebanon were recovered and identified. The samples were heat killed and subjected to DNA extraction. Spoligotyping was performed using microbeads from TB-SPOL Kit and the fluorescence intensity was measured using Luminex 200®. Generated patterns were assigned to families using the SITVIT2 international database of the Pasteur Institute of Guadeloupe and compared.
 Results: The spoligotyping of the 49 MTB isolates revealed that 31 isolates belonged to Lineage 4 (Euro-American, 63.3%), 12 to Lineage 3 (East- African Indian, 24.5%), 3 to Lineage 2 (East Asian, 6%) and 2 were unknown. Over half of the genotypes (16 of 30) harbored SIT127 supposed to belong to the L4.5 sublineage. One isolate belonging to the rare Manu-Ancestor SIT523 was recovered for the first time in Lebanon, being associated with highly virulent extensively drug-resistant (XDR) MTB phenotype.
 Conclusion: The application of the Spoligotyping Multiplex Luminex® method is an efficient, discriminatory and rapid method to use for first-lane genotyping of MTB isolates. Though humble numbers were tested, this study is one of the first to describe the genomic diversity and epidemiology of MTB isolates of Lebanon, and suggests an increasing prevalence of SIT127 in the country.
Mansour Kargarpour Kamakoli, Ghazaleh Farmanfarmaei, Morteza Masoumi, Sharareh Khanipour, Safoora Gharibzadeh, Christophe Sola, Abolfazl Fateh, Seyed Davar Siadat, Guislaine Refregier, and Farzam Vaziri
Elsevier BV
C. Pierre-Audigier, C. Talla, A-K. Alame-Emane, B. Audigier, N. Grall, R. Ruimy, A. Andremont, V. Cadet-Daniel, C. Sola, H. Takiff,et al.
International Union Against Tuberculosis and Lung Disease
SETTING: Tuberculosis (TB) incidence is declining overall in France, but not in Paris where some areas remain relative hot spots for TB.OBJECTIVES: To obtain a better knowledge of local TB epidemiology in order to facilitate control measures.DESIGN: Analysis of demographic data of TB patients diagnosed at the Bichat-Claude Bernard Hospital from 2007 to 2016, with spoligotyping of Mycobacterium tuberculosis complex isolates.RESULTS: During the study period, 1096 TB patients were analysed. The incidence of TB diagnosis was stable, averaging 115 patients per year, predominantly males (71%), foreign-born (81%), with pulmonary TB (77%) and negative HIV serology (88%). The mean age of foreign-born TB patients decreased over the study period, most significantly in recent arrivals in France, whose average age decreased by two years (P = 0.001). The time period between arrival in France and being diagnosed with active TB decreased annually significantly by 0.75 years (P = 0.02). The proportion of L4.6.2/Cameroon and L2/Beijing sub-lineages increased annually by 0.7% (P < 0.05). Multi-drug resistant strains, representing 4% of all strains, increased annually by 0.75% (P = 0.03)CONCLUSION: The number of TB patients remained high in northern Paris and the surrounding suburbs, suggesting the need for increased control measures.
Bernice J. Klotoe, Natalia Kurepina, Elena Zholdibayeva, S. Panaiotov, Barry N. Kreiswirth, Richard Anthony, Christophe Sola, and Guislaine Refrégier
Elsevier BV
Regina Bones Barcellos, Isabela Neves de Almeida, Elisangela Costa da Silva, Harrison Magdinier Gomes, Lida Jouca de Assis Figueredo, Maria Laura Halon, Elis Regina Dalla Costa, Ícaro Rodrigues dos Santos, Maria Cláudia Vater, Suely Alves,et al.
Springer Science and Business Media LLC
Abstract Background Molecular tests can allow the rapid detection of tuberculosis (TB) and multidrug-resistant TB (MDR-TB). TB-SPRINT 59-Plex Beamedex® is a microbead-based assay developed for the simultaneous spoligotyping and detection of MDR-TB. The accuracy and cost evaluation of new assays and technologies are of great importance for their routine use in clinics and in research laboratories. The aim of this study was to evaluate the performance of TB-SPRINT at three laboratory research centers in Brazil and calculate its mean cost (MC) and activity-based costing (ABC). Methods TB-SPRINT data were compared with the phenotypic and genotypic profiles obtained using Bactec™ MGIT™ 960 system and Genotype® MTBDRplus, respectively. Results Compared with MGIT, the accuracies of TB-SPRINT for the detection of rifampicin and isoniazid resistance ranged from 81 to 92% and 91.3 to 93.9%, respectively. Compared with MTBDRplus, the accuracies of TB-SPRINT for rifampicin and isoniazid were 99 and 94.2%, respectively. Moreover, the MC and ABC of TB-SPRINT were USD 127.78 and USD 109.94, respectively. Conclusion TB-SPRINT showed good results for isoniazid and rifampicin resistance detection, but still needs improvement to achieve In Vitro Diagnostics standards.
Vanina Guernier-Cambert, Tanya Diefenbach-Elstob, Bernice J. Klotoe, Graham Burgess, Daniel Pelowa, Robert Dowi, Bisato Gula, Emma S. McBryde, Guislaine Refrégier, Catherine Rush,et al.
Springer Science and Business Media LLC
AbstractTuberculosis remains the world’s leading cause of death from an infectious agent, and is a serious health problem in Papua New Guinea (PNG) with an estimated 36,000 new cases each year. This study describes the genetic diversity of Mycobacterium tuberculosis among tuberculosis patients in the Balimo/Bamu region in the Middle Fly District of Western Province in PNG, and investigates rifampicin resistance-associated mutations. Archived Ziehl-Neelsen-stained sputum smears were used to conduct microbead-based spoligotyping and assess genotypic resistance. Among the 162 samples included, 80 (49.4%) generated spoligotyping patterns (n = 23), belonging predominantly to the L2 Lineage (44%) and the L4 Lineage (30%). This is consistent with what has been found in other PNG regions geographically distant from Middle Fly District of Western Province, but is different from neighbouring South-East Asian countries. Rifampicin resistance was identified in 7.8% of the successfully sequenced samples, with all resistant samples belonging to the L2/Beijing Lineage. A high prevalence of mixed L2/L4 profiles was suggestive of polyclonal infection in the region, although this would need to be confirmed. The method described here could be a game-changer in resource-limited countries where large numbers of archived smear slides could be used for retrospective (and prospective) studies of M. tuberculosis genetic epidemiology.
Emilyn Costa Conceição, Guislaine Refregier, Harrison Magdinier Gomes, Xavier Olessa-Daragon, Francesc Coll, Noël Harijaona Ratovonirina, Voahangy Rasolofo-Razanamparany, Maria Luiza Lopes, Dick van Soolingen, Liliana Rutaihwa,et al.
Elsevier BV
B. J. Klotoe, S. Kacimi, E. Costa-Conceicão, H. M. Gomes, R. B. Barcellos, S. Panaiotov, D. Haj Slimene, N. Sikhayeva, S. Sengstake, A. R. Schuitema,et al.
Springer Science and Business Media LLC
Fermín Acosta, Juan Agapito, Andrea Maurizio Cabibbe, Tatiana Cáceres, Christophe Sola, Laura Pérez-Lago, Estefanía Abascal, Marta Herranz, Erika Meza, Bernice Klotoe,et al.
Centers for Disease Control and Prevention (CDC)
We performed a cross-border molecular epidemiology analysis of multidrug-resistant tuberculosis in Peru, Spain, and Italy. This analysis revealed frequent transmission in Peru and exportation of a strain that recreated similar levels of transmission in Europe during 2007–2017. Transnational efforts are needed to control transmission of multidrug-resistant tuberculosis globally.
Marwa Haddaoui, Christophe Sola, Noureddine Raouafi, and Hafsa Korri-Youssoufi
Elsevier BV
Lívia Maria Pala Anselmo, Emilyn Costa Conceição, Evangelina Namburete, Cinara Feliciano, Silvana Spindola, Christophe Sola, and Valdes Roberto Bollela
FapUNIFESP (SciELO)
INTRODUCTION
Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country.
METHODS
We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed.
RESULTS
Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases.
CONCLUSIONS
Beira and Mozambique share the same population genetic structure of M. tuberculosis.
Barbara Molina-Moya, Mulualem Agonafir, Silvia Blanco, Russell Dacombe, Michel K. Gomgnimbou, Lizania Spinasse, Meissiner Gomes-Fernandes, Daniel G. Datiko, Thomas Edwards, Luis E. Cuevas,et al.
Springer Science and Business Media LLC
AbstractThe worldwide dissemination of Mycobacterium tuberculosis strains has led to the study of their genetic diversity. One of the most used genotyping methods is spoligotyping, based on the detection of spacers in the clustered regularly interspaced short palindromic repeats (CRISPR) locus. This study assessed the performance of a microbead-based spoligotyping assay using samples extracted from Ziehl-Neelsen-stained smear-microscopy preparations and described the genetic diversity of Mycobacterium tuberculosis among new TB patients in Southern Nations, Nationalities and Peoples’ Region (SNNPR) in Ethiopia. Among the 91 samples analysed, 59 (64.8%) generated spoligotyping patterns. Fifty (84.7%) samples were classified into 12 clusters (mostly Lineage 4 or 3) comprising 2–11 samples and nine had unique spoligotyping patterns. Among the 59 spoligotyping patterns, 25 belonged to the T1 sublineage, 11 to the T3-ETH, 5 to the URAL, 4 to the H3 and 14 to other L4 sublineages. There was a remarkable variation in genetic distribution in SNNPR compared to other regions of the country. Microbead-based spoligotyping is an easy-to-perform, high-throughput assay that can generate genotyping information using material obtained from smear microscopy preparations. The method provides an opportunity to obtain data of the M. tuberculosis genetic epidemiology in settings with limited laboratory resources.