Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis

PubMed ID: 10639358Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB- susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance- associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB- resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance- associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in the iniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype

Biomimetics: its practice and theory

Biomimetics, a name coined by Otto Schmitt in the 1950s for the transfer of ideas and analogues from biology to technology, has produced some significant and successful devices and concepts in the past 50 years, but is still empirical. We show that TRIZ, the Russian system of problem solving, can be adapted to illuminate and manipulate this process of transfer. Analysis using TRIZ shows that there is only 12% similarity between biology and technology in the principles which solutions to problems illustrate, and while technology solves problems largely by manipulating usage of energy, biology uses information and structure, two factors largely ignored by technology