Multidrug-resistant mycobacterium tuberculosis of the Latin American mediterranean lineage, wrongly identified as mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), causing active tuberculosis in South Brazil
Dalla Costa E.R.,Fundaao Estadual de Produao e Pesquisa em Saude FEPPS |
Vasconcelos S.E.G.,Instituto Oswaldo Cruz |
Esteves L.S.,Fundaao Estadual de Produao e Pesquisa em Saude FEPPS |
Esteves L.S.,Lutheran University of Brazil |
And 15 more authors.
Journal of Clinical Microbiology | Year: 2015
We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RDRio, and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n=8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C(17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers. © 2015, American Society for Microbiology.
Costa E.R.D.,Fundacao Estadual de Producao e Pesquisa em Saude FEPPS |
Lazzarini L.C.O.,Federal University of Rio de Janeiro |
Perizzolo P.F.,Fundacao Estadual de Producao e Pesquisa em Saude FEPPS |
Diaz C.A.,Oswaldo Cruz Institute |
And 14 more authors.
Journal of Clinical Microbiology | Year: 2013
Spoligotyping has shown Mycobacterium tuberculosis strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RDRio, widespread in Brazil. Moreover, recent data also indicate that RDRio is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RD Rio and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RDRio alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS6110-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RDRio. No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RD Rio strain (P=0.0015). Altogether, RDRio was responsible for 38% of all TB cases. These data support and confirmed previous findings that RDRio is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RDRio is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations. © 2013, American Society for Microbiology.