🔬 A groundbreaking study utilizing whole genome sequencing (WGS) has provided the first in-depth look at the genetic landscape of Mycobacterium tuberculosis in the Philippines. The research offers critical insights into the dominant TB strain circulating in the country—the Manila strain—and its associated drug-resistance mutations. These findings underscore the importance of integrating genomic tools into national TB surveillance and treatment strategies.

🧪 Genomic Mapping of TB in the Philippines

The Philippines is one of the highest TB burden countries in Southeast Asia, facing a growing threat from multidrug-resistant tuberculosis (MDR-TB). To better understand the genetic makeup of TB strains circulating in the country, researchers conducted WGS on 178 clinical isolates collected during the 2012 National Drug Resistance Survey.

Key findings included:

• 80% (143/178) of isolates belonged to lineage 1, specifically the EAI2-Manila clade, confirming its predominance in the Philippines.
• The remaining isolates were classified under lineages 4 (18.5%) and 2 (1.1%).
• 19.1% (34/178) of the isolates were confirmed as MDR-TB through both laboratory drug susceptibility testing and in-silico genomic analysis.
• Genetic similarities among some isolates suggested possible local transmission clusters, even though the samples were collected across diverse geographic regions.

🌍 Manila Strain’s Global Connection

Using a phylogenetic tree constructed from over 17,000 global M. tuberculosis sequences, researchers found that Philippine strains were closely related to those observed internationally, particularly in Thailand, where Manila-like strains appear to have been exported and further evolved.

The team identified 197 genetic markers (SNPs) specific to the Manila strain, 115 of which led to changes in amino acids. These mutations could be used to develop a molecular barcode for surveillance and outbreak tracking.

🧬 Resistance Mechanisms and Novel Mutations

The WGS analysis uncovered 68 mutations linked to resistance against 10 anti-TB drugs, most of which have been previously reported globally. However, the study also detected novel mutations in the gid and rrs genes, potentially associated with streptomycin resistance. These findings are significant, as streptomycin remains part of some treatment regimens.

In particular, mutations that alter the S-adenosyl-L-methionine (SAM) binding motif of the gid gene could disrupt bacterial protein synthesis, thereby contributing to resistance. These newly discovered mutations warrant further experimental validation.

Importantly, there was no evidence of extensively drug-resistant TB (XDR-TB) among the isolates studied, and resistance to fluoroquinolones was rare.

📉 Implications for TB Control and Diagnostics

The Philippine National Tuberculosis Program continues to face significant challenges in diagnosing and managing MDR-TB, compounded by under-resourced healthcare infrastructure. The study demonstrates that WGS can:

• Improve drug resistance prediction accuracy
• Help identify local and cross-border transmission events
• Support the development of region-specific diagnostic tools
• Serve as a basis for creating a genomic reference database for future surveillance and clinical decision-making

By transitioning from limited molecular diagnostics (e.g., GeneXpert and line probe assays) to WGS-based approaches, healthcare providers can analyze the full genome (~4.4 Mb) for deeper insights into resistance profiles, strain evolution, and public health risks.

🔬 A Step Toward Precision Public Health

This study marks the largest WGS investigation of the Manila TB strain to date and confirms that the genetic diversity and resistance patterns of Philippine TB strains are in line with global trends. It also highlights the feasibility of using WGS to strengthen epidemiological surveillance, particularly in resource-limited, high-burden countries like the Philippines.

The results provide a blueprint for future genomic studies, help identify areas for targeted intervention, and pave the way for integrating genomics into routine TB control programs.

📖 Reference

Nguyen LTN, et al. (2019). Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines. Scientific Reports. https://pmc.ncbi.nlm.nih.gov/articles/PMC6594935