title: Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Stanford University Medical Center, Stanford, California, USA. sgagneux@systemsbiology.org
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gagneux
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Burgos
authors.forename: Kathryn
authors.initials: K
authors.lastname: DeRiemer
authors.forename: Antonio
authors.initials: A
authors.lastname: Encisco
authors.forename: Samira
authors.initials: S
authors.lastname: Muñoz
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Hopewell
authors.forename: Peter M
authors.initials: PM
authors.lastname: Small
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Pym
mesh_terms: D000483:Alleles; D000995:Antitubercular Agents / Q000627:therapeutic use*; D019070:Cell Lineage / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics* / Q000635:transmission*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid