Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis
Division of Infectious Diseases and Geographic Medicine, Stanford University Medical Center, Stanford, CA, United States; Institute for Systems Biology, Seattle, WA, United States; Department of Internal Medicine, Division of Infectious Diseases, University of New Mexico, Albuquerque, NM, United States; Veterans Affairs Medical Center, Albuquerque, NM, United States; School of Medicine, University of California Davis, Davis, CA, United States; Unidad de Investigacion Medica de Zacatecas, Zacatecas, Mexico; Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, United States; Bill and Melinda Gates Foundation, Seattle, WA, United States; Unit for Clinical and Biomedical TB Research, South African Medical Research Council, Durban, South Africa
Understanding the ecology of drug-resistant pathogens is essential for devising rational programs to preserve the effective lifespan of antimicrobial agents and to abrogate epidemics of drug-resistant organisms. Mathematical models predict that strain fitness is an important determinant of multidrug-resistant Mycobacterium tuberculosis transmission, but the effects of strain diversity have been largely overlooked. Here we compared the impact of resistance mutations on the transmission of isoniazid-resistant M. tuberculosis in San Francisco during a 9-y period. Strains with a KatG S315T or inhA promoter mutation were more likely to spread than strains with other mutations. The impact of these mutations on the transmission of isoniazid-resistant strains was comparable to the effect of other clinical determinants of transmission. Associations were apparent between specific drug resistance mutations and the main M. tuberculosis lineages. Our results show that in addition to host and environmental factors, strain genetic diversity can influence the transmission dynamics of drug-resistant bacteria. © 2006 Gagneux et al.
isoniazid; adult; aged; allele; antibiotic resistance; article; bacterial genetics; bacterial strain; bacterial transmission; controlled study; female; gene mutation; gene sequence; genetic variability; human; major clinical study; male; Mycobacterium tuberculosis; nonhuman; promoter region; United States; Bacteria (microorganisms); Mycobacterium tuberculosis