Clinical Relevance of Mycobacterium tuberculosis plcD Gene Mutations

• Published in: American journal of respiratory and critical care medicine Vol. 171; no. 12; pp. 1436 - 1442
• Main Authors: Yang, Zhenhua, Yang, Dong, Kong, Ying, Zhang, Lixin, Marrs, Carl F, Foxman, Betsy, Bates, Joseph H, Wilson, Frank, Cave, M. Donald
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15-06-2005; American Lung Association; American Thoracic Society
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Southern; Cardiology. Vascular system; Disease Progression; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; DNA Fingerprinting; Female; Genes, Bacterial - genetics; Genetic Markers - genetics; Hematologic and hematopoietic diseases; Humans; I. Tuberculosis; Intensive care medicine; Male; Medical sciences; Middle Aged; Mutation; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; Platelet diseases and coagulopathies; Polymerase Chain Reaction; Sensitivity and Specificity; Sequence Analysis, DNA; Severity of Illness Index; Tuberculosis - microbiology; Tuberculosis - physiopathology; Type C Phospholipases - genetics; Type C Phospholipases - metabolism; Intensive care; Pathogenesis; Virulence; Mycobacterial infection; virulence factors; Infection; extrathoracic tuberculosis; Tuberculosis; Mycobacterium tuberculosis; Mycobacteriales; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes; Mutation; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200408-1147OC

To identify Mycobacterium tuberculosis virulence factors, we integrated comparative genomics and epidemiologic data analysis to investigate the relationship between certain genomic insertions and deletions in the phospholipase-C gene D (plcD) with the clinical presentation of tuberculosis (TB). Four hundred ninety-six well-characterized M. tuberculosis clinical isolates were studied. Approximately 30% (147) of the isolates had an interruption of the plcD gene. Patients infected with the plcD mutant were twice as likely to have extrathoracic disease as those infected by a strain without an interruption (adjusted odds ratio, 2.19; 95% confidence interval, 1.27, 3.76). When we limited the analysis to the 275 isolates with distinct DNA fingerprint patterns, we observed the same association (adjusted odds ratio, 2.74; 95% confidence interval, 1.35, 5.56). Furthermore, the magnitude of the association appeared to differ with the type of extrathoracic TB. Our findings suggest that the plcD gene of M. tuberculosis is potentially involved in the pathogenesis of TB, and the clinical presentation of the disease may be influenced by the genetic variability of the plcD region.