Successful expansion of Mycobacterium tuberculosis Latin American and Mediterranean sublineage (L4.3/LAM) in Tunisia mainly driven by a single, long-established clonal complex

Skhairia, Mohamed Amine; Dekhil, Naira; Mhenni, Besma; Fradj, Saloua Ben; Mardassi, Helmi

doi:10.1016/j.ijid.2020.11.195

Cited by 7 publications

(7 citation statements)

References 34 publications

(47 reference statements)

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“…These results confirm previous findings reporting circulation of Beijing lineage only in limited locations of the Americas like Cuba, Colombia, and Peru ( 24 ). Nevertheless, permanent genetic surveillance should be implemented within the Ecuadorian national TB surveillance program to identify active transmission clusters, as has been described, for instance, in Panama ( 37 ) or Tunisia ( 27 , 28 ). This is especially relevant considering the presence of hot spots for active transmission clusters like prisons in Latin American region ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, information from MTBC strains from Ecuador and Colombia was retrieved from the bibliography, as it has been done in similar studies ( 27 , 28 ). For the phylogenetic analysis described below, 190 MTBC strains from Colombia for the years 2012–2014 ( 4 ) and 385 MTBC strains from Ecuador from the years 2012–2016 ( 9 , 26 ) were included in the study.…”

Section: Methodsmentioning

confidence: 99%

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A first insight into tuberculosis transmission at the border of Ecuador and Colombia: a retrospective study of the population structure of Mycobacterium tuberculosis in Esmeraldas province

Castro-Rodriguez,

Espinoza-Andrade,

Franco-Sotomayor

et al. 2024

Front. Public Health

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ObjectiveTuberculosis (TB) is a major public health concern in Ecuador and Colombia, considering that both countries are high-burden TB settings. Molecular epidemiology is crucial to understand the transmission dynamics of Mycobacterium tuberculosis complex (MTBC) and to identify active transmission clusters of regional importance.MethodsWe studied the potential transmission of TB between Colombia and Ecuador through the analysis of the population structure of MTBC lineages circulating in the Ecuadorian province of Esmeraldas at the border with Colombia. A total of 105 MTBC strains were characterized by 24-loci MIRU-VNTR and spoligotyping.ResultsMTBC lineage 4 is only present in Esmeraldas; no MTBC strains belonging to Lineage 2–sublineage Beijing were found despite its presence in other provinces of Ecuador and, in Colombia. Genotyping results revealed a high degree of diversity for MTBC in Esmeraldas: Neither active transmission clusters within this province nor including MTBC strains from Colombia or other provinces of Ecuador were found.ConclusionOur data suggest that tuberculosis dynamics in this rural and isolated area may be not related to highly transmitted strains but could be influenced by other health determinants that favor TB relapse such as poverty and poor health system access. Further studies including a larger number of MTBC strains from Esmeraldas are necessary to test this hypothesis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A first insight into tuberculosis transmission at the border of Ecuador and Colombia: a retrospective study of the population structure of Mycobacterium tuberculosis in Esmeraldas province

Castro-Rodriguez,

Espinoza-Andrade,

Franco-Sotomayor

et al. 2024

Front. Public Health

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“…Illumina paired-end sequencing data were analysed using a pipeline composed of open source software as described previously [ 14 ]. Briefly, raw sequencing data were checked for quality control using FASTQC [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia

Dekhil,

Mardassi

2024

Antimicrob Resist Infect Control

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Background To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s. Methods We performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001–2016. Results The data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951–1985), from where it spread to other regions by 1992 (95% CI 1980–1996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype. Conclusions WGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26 years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures.

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“…We have shown previously that the success of L4.3/LAM in Tunisia stems mainly from the expansion of a single clonal complex (CC), termed TUN4.3_CC1 ( Skhairia et al, 2021 ), which represents 61.5% of the L4.3/LAM population. Unlike the much less prevalent TUN4.3_CC2 (14.68%), TUN4.3_CC1 lacks RD115 deletion, the earliest deletion that occurred in the L4.3/LAM sublineage, suggesting its relative ancient origin.…”

Section: Introductionmentioning

confidence: 99%

“…To investigate the phylogenetic placement of Tunisian L4.3/LAM clinical strains in a worldwide context, we used a globally distributed genome dataset consisting of 278 L4.3/LAM isolates, available at the European Nucleotide Archive (ENA), covering a wide temporal and geographic range ( Supplementary Table S1 ). This dataset includes 41 genomes consisting of TUN4.3_CC1 ( n = 17), TUN4.3_CC2 ( n = 11), and 3 singletons (SING) that we have previously reported ( Skhairia et al, 2021 ), and ten published genomes ( Bouzouita et al, 2019 ), nine of which were found to belong to the major TUN4.3_CC1, and one genome being related to TUN4.3_CC2. Genomic data were analyzed using an in-house automated pipeline including open source softwares.…”

Section: Introductionmentioning

confidence: 99%

Genomic changes underpinning the emergence of a successful Mycobacterium tuberculosis Latin American and Mediterranean clonal complex

Dekhil

Mardassi

2023

Front. Microbiol.

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IntroductionThe Latin American and Mediterranean sublineage (L4.3/LAM) is the most common generalist sublineage of Mycobacterium tuberculosis lineage 4 (L4), yet certain L4.3/LAM genotypes appear to be confined to particular geographic regions. This is typically the case of a L4.3/LAM clonal complex (CC), TUN4.3_CC1, which is the most preponderant in Tunisia (61.5% of L4.3/LAM).MethodsHere, we used whole-genome sequencing data of 346 globally distributed L4 clinical strains, including 278 L4.3/LAM isolates, to reconstruct the evolutionary history of TUN4.3_CC1 and delineate critical genomic changes underpinning its success.Results and DiscussionPhylogenomic coupled to phylogeographic analyses indicated that TUN4.3_CC1 has evolved locally, being confined mainly to North Africa. Maximum likelihood analyses using the site and branch-site models of the PAML package disclosed strong evidence of positive selection in the gene category “cell wall and cell processes” of TUN4.3_CC1. Collectively, the data indicate that TUN4.3_CC1 has inherited several mutations, which could have potentially contributed to its evolutionary success. Of particular interest are amino acid replacements at the esxK and eccC2 genes of the ESX/Type VII secretion system, which were found to be specific to TUN4.3_CC1, being common to almost all isolates. Because of its homoplastic nature, the esxK mutation could potentially have endowed TUN4.3_CC1 with a selective advantage. Moreover, we noticed the occurrence of additional, previously described homoplasic nonsense mutations in ponA1 and Rv0197. The mutation in the latter gene, a putative oxido-reductase, has previously been shown to be correlated with enhanced transmissibility in vivo. In sum, our findings unveiled several features underpinning the success of a locally evolved L4.3/LAM clonal complex, lending further support to the critical role of genes encoded by the ESX/type VII secretion system.

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Successful expansion of Mycobacterium tuberculosis Latin American and Mediterranean sublineage (L4.3/LAM) in Tunisia mainly driven by a single, long-established clonal complex

Cited by 7 publications

References 34 publications

A first insight into tuberculosis transmission at the border of Ecuador and Colombia: a retrospective study of the population structure of Mycobacterium tuberculosis in Esmeraldas province

A first insight into tuberculosis transmission at the border of Ecuador and Colombia: a retrospective study of the population structure of Mycobacterium tuberculosis in Esmeraldas province

On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia

Genomic changes underpinning the emergence of a successful Mycobacterium tuberculosis Latin American and Mediterranean clonal complex

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