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Biomedical subjects

Midori Kato-Maeda

Publications and source records attributed to Midori Kato-Maeda.

8 recordsLinked to original sources

Variable host-pathogen compatibility in Mycobacterium tuberculosis.

Mycobacterium tuberculosis remains a major cause of morbidity and mortality worldwide. Studies have reported human pathogens to have geographically structured population genetics, some of which have been linked to ancient human migrations. However, no study has addressed the potential evolutionary consequences of such longstanding human-pathogen associations. Here, we demonstrate that the global population structure of M. tuberculosis is defined by six phylogeographical lineages, each associated with specific, sympatric human populations. In an urban cosmopolitan environment, mycobacterial lineages were much more likely to spread in sympatric than in allopatric patient populations. Tuberculosis cases that did occur in allopatric hosts disproportionately involved high-risk individuals with impaired host resistance. These observations suggest that mycobacterial lineages are adapted to particular human populations. If confirmed, our findings have important implications for tuberculosis control and vaccine development.

Adaptation, Physiological↗

Use of rapid genomic deletion typing to monitor a tuberculosis outbreak within an urban homeless population.

Beginning in mid-2002, a large tuberculosis outbreak occurred among homeless persons in King County, Washington. In order to further monitor the outbreak following its peak in 2003, Mycobacterium tuberculosis isolates from all new King County tuberculosis (TB) patients in 2004 and the first half of 2005 (n = 220) were genotyped by using a rapid comparative genomics-based (genomic deletion-typing) approach, with confirmation by mycobacterial interspersed repetitive units and repetitive-sequence-based PCR (rep-PCR). Results were compared to retrospective genotypic data from 1995 to 2003. The outbreak strain SBRI9, which was not seen among King County homeless persons prior to 2002, accounted for 16 out of 30 TB cases (53%) within this population in 2002. This trend continued with 27 out of 35 cases (77%) caused by the outbreak strain in 2003, 11 out of 13 cases (85%) caused by the outbreak strain in 2004, and 4 out of 10 cases (40%) caused by the outbreak strain in the first 5 months of 2005. Thus, the outbreak strain remained well established within this homeless population throughout the study period. At least four SBRI9 cases were in people who had previously been infected by other strains. The novel PCR-based strain-typing approach used in this investigation proved to be cost-effective and very rapid. In most cases, it was possible to analyze DNA extracted directly from primary isolation (Mycobacterium growth indicator tube) cultures submitted by clinical laboratories, a feature that markedly reduced the delay between diagnosis and strain typing results. This rapid turnaround facilitated public health efforts to prevent new outbreaks involving this strain.

Bacterial Typing Techniques↗

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

To better understand genome function and evolution in Mycobacterium tuberculosis, the genomes of 100 epidemiologically well characterized clinical isolates were interrogated by DNA microarrays and sequencing. We identified 68 different large-sequence polymorphisms (comprising 186,137 bp, or 4.2% of the genome) that are present in H37Rv, but absent from one or more clinical isolates. A total of 224 genes (5.5%), including genes in all major functional categories, were found to be partially or completely deleted. Deletions are not distributed randomly throughout the genome but instead tend to be aggregated. The distinct deletions in some aggregations appear in closely related isolates, suggesting a genomically disruptive process specific to an individual mycobacterial lineage. Other genomic aggregations include distinct deletions that appear in phylogenetically unrelated isolates, suggesting that a genomic region is vulnerable throughout the species. Although the deletions identified here are evidently inessential to the causation of disease (they are found in active clinical cases), their frequency spectrum suggests that most are weakly deleterious to the pathogen. For some deletions, short-term evolutionary pressure due to the host immune system or antibiotics may favor the elimination of genes, whereas longer-term physiological requirements maintain the genes in the population.

Evolution, Molecular↗

Genomic analysis distinguishes Mycobacterium africanum.

Mycobacterium africanum is thought to comprise a unique species within the Mycobacterium tuberculosis complex. M. africanum has traditionally been identified by phenotypic criteria, occupying an intermediate position between M. tuberculosis and M. bovis according to biochemical characteristics. Although M. africanum isolates present near-identical sequence homology to other species of the M. tuberculosis complex, several studies have uncovered large genomic regions variably deleted from certain M. africanum isolates. To further investigate the genomic characteristics of organisms characterized as M. africanum, the DNA content of 12 isolates was interrogated by using Affymetrix GeneChip. Analysis revealed genomic regions of M. tuberculosis deleted from all isolates of putative diagnostic and biological consequence. The distribution of deleted sequences suggests that M. africanum subtype II isolates are situated among strains of "modern" M. tuberculosis. In contrast, other M. africanum isolates (subtype I) constitute two distinct evolutionary branches within the M. tuberculosis complex. To test for an association between deleted sequences and biochemical attributes used for speciation, a phenotypically diverse panel of "M. africanum-like" isolates from Guinea-Bissau was tested for these deletions. These isolates clustered together within one of the M. africanum subtype I branches, irrespective of phenotype. These results indicate that convergent biochemical profiles can be independently obtained for M. tuberculosis complex members, challenging the traditional approach to M. tuberculosis complex speciation. Furthermore, the genomic results suggest a rational framework for defining M. africanum and provide tools to accurately assess its prevalence in clinical specimens.

Genome, Bacterial↗

Tuberculosis-related deaths within a well-functioning DOTS control program.

To describe the molecular epidemiology of tuberculosis (TB)-related deaths in a well-managed program in a low-HIV area, we analyzed data from a cohort of 454 pulmonary TB patients recruited between March 1995 and October 2000 in southern Mexico. Patients who were sputum acid-fast bacillus smear positive underwent clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) and received treatment from the local directly observed treatment strategy (DOTS) program. After an average of 2.3 years of follow-up, death was higher for clustered cases (28.6 vs. 7%, p=0.01). Cox analysis revealed that TB-related mortality hazard ratios included treatment default (8.9), multidrug resistance (5.7), recently transmitted TB (4.1), weight loss (3.9), and having less than 6 years of formal education (2). In this community, TB is associated with high mortality rates.

Adolescent↗

[Increasing trend of antimicrobial drug-resistance in organisms causing bacteremia at a tertiary-care hospital: 1995 to 2000].

We described the trends of drug-resistant organisms isolated in blood cultures from patients detected in a teaching hospital from 1995 to 2000. We found an increase in the number of clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp, Serratia spp, Staphylococcus aureus, S. epidermidis and Enterococcus spp, resistant to antibiotics commonly used to treat infections caused by these organisms. The frequency of gram-negative bacilli resistant to third-generation cephalosporins and quinolones increased during the period of study, and in 2000 more than 20% of the isolates were resistant. In contrast, the frequency of resistance to aminoglycosides and carbapenems was less than 20%. The frequency of resistant staphylococci increased exuberantly fifty fold to quinolones and five fold to oxacillin during the study period, therefore in 2000, 26.1% of S. aureus isolates and 61% of S. epidermidis were resistant to oxacillin. The frequency of resistant enterococci also increased, and in 2000, 50% were resistant to ampicillin, and 37.5% to gentamicin. The increase of drug resistant organisms isolated in blood had a direct impact in the empirical treatment of severely infected patients in our hospital. It is important to continuously supervise antibiotic use, and to adopt more strict control measures to decrease the frequency of infections caused by drug resistant organisms.

Bacteremia↗