Characterization of the Manila Family of Mycobacterium tuberculosis

Abstract

Forty-eight Mycobacterium tuberculosis strains were obtained from patients living in metropolitan Manila, Republic of the Philippines. Three molecular typing methods, IS6110 restriction fragment length polymorphism, spoligotyping, and DNA sequencing of the oxyR, gyrA, and katG loci, established that these strains have restricted diversity and are members of a related genetic group of organisms. Comparison of the DNA fingerprint patterns with those in international databases confirmed the uniqueness of this group of isolates, which we designate the Manila family of M. tuberculosis.The advent of IS6110-based restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis has led to fingerprinting studies throughout the world (13, 16). These studies have provided insight on the transmission of tuberculosis within and among different geographical areas of the world (10, 16). One finding of IS6110 DNA fingerprinting is that the population structure of M. tuberculosis differs in regions in that some geographical areas are associated with families or groups of related isolates, such as the Beijing, Haarlem, and African genotype families (2,5,7,8,15 Microbiol. 1995Microbiol. , abstr. U-4, p. 117, 1995. Additional DNA typing technologies, such as spoligotyping (6), analysis of the pseudogene oxyR (12), polymorphic GC-rich sequence RFLP (9), and typing of variable numbers of tandem repeats (1) confirmed these family groupings of M. tuberculosis.Since we noticed that tuberculosis isolates from Filipinos, which account for 50% of the M. tuberculosis isolates from foreign-borne patients in Hawaii (State of Hawaii Department of Health data, www.hawaiistate/health/tuberculosis, 2001), had related spoligotyping patterns, we decided to directly investigate isolates from Manila, Republic of the Phillipines (J. T. Douglas, L. Qian, J. C. Montoya, S. Sreevatsan, J. M. Musser, and J. D. A. van Embden, Abstr. 97th Gen. Meet. Am. Soc. Microbiol., abstr. U-166, p. 572, 1997). Manila is the largest city in the Philippines (about 10 million people); it has a high population density and socioeconomic problems, and tuberculosis is highly endemic. Manila is also geographically isolated within an island nation, which could be a fertile ground for clonal expansion of M. tuberculosis. Because little is known about the population structure of tuberculosis in the Philippines, we subjected a random sample of M. tuberculosis isolates originating in Manila to various molecular typing techniques to search for genetic markers that might be useful in studying M. tuberculosis isolates recovered from immigrant populations within Hawaii.The Tuberculosis Study Group at the Research Institute for Tropical Medicine and the Philippine General Hospital provided 48 M. tuberculosis isolates from separate individuals in the metropolitan Manila area. Initially 18 isolates were collected in December 1995, followed by 30 isolates 8 months later. Of these, 35 came with some demographic data. These isolates were from 18 males and 17 females. Th...

Analysis ofMycobacterium tuberculosisGenotypes in Madrid and Identification of Two New Families Specific to Spain-Related Settings

“…In Tanzania, McHugh et al identified the Kilimanjaro 1 TB lineage, a characteristically Tanzanian clone, which may be a sublineage of the Central Asian 1-Delhi lineage (14). In the Philippines, Douglas et al and Sola et al described the Manila family, (also designated as the East African-Indian 2 genotype), which is part of the largest EAI superfamily (4,6). Recently, the Cameroon family of TB bacilli was also identified (15).…”

“…The creation of international databases has revealed the clonal structure of M. tuberculosis populations in different geographic settings and has also defined superfamilies that are specific to certain countries (4,14,15). In this regard, the existence of an international database on spoligotyping (for spacer oligonucleotide typing), a PCR-based method that relies on a genetic locus called the direct repeat (11), which is highly polymorphic worldwide, has allowed some of the major superfamilies of M. tuberculosis to be described (6,7).…”

Contribution of spoligotyping to the characterization of the population structure of Mycobacterium tuberculosis isolates in Portugal

“…Also, the organization of an international spoligotype database has made it possible to have a global view of the geographical distribution of genotypes (Sola et al, 2001;Filliol et al, 2002Filliol et al, , 2003. A larger number of studies on M. tuberculosis population structure have permitted distinction between spoligotype families of high global distribution, such as the Beijing/W genotype, as compared to those with regional specificity Douglas et al, 2003;Niobe-Eyangoh et al, 2004;Garcia de Viedma et al, 2005;McHugh et al, 2005;Brudey et al, 2006).…”

Functional and evolutionary genomics of Mycobacterium tuberculosis : Insights from genomic deletions in 100 strains

“…Thus, aggregations 110b-110c and 236-239 are very likely to be due to genetic events resulting in local genomic instability in specific lineages. Aggregation 236-239 is confined to the so-called ''Manila'' clade (28), and is likely to result from a genetic event that occurred in the ancestor of these isolates.…”