Application of molecular genetic methods in macrolide, lincosamide and streptogramin resistance diagnostics and in detection of drug-resistant Mycobacterium tuberculosis.
Antimicrobial susceptibility testing has traditionally been based on measurements of minimal inhibitory concentrations of antimicrobials. Molecular genetic studies on antimicrobial resistance have produced a great deal of genetic information which can be used for diagnosis of antimicrobial resistance determinants. Bacteria can acquire resistance to macrolides, lincosamides and streptogramin antibiotics by modification of the target site of the drugs, by active efflux of the drugs, and by inactivation of the drugs. The genetic backgrounds of these resistance mechanisms are well known and several molecular methods for detection of resistance determinants have been developed. Outbreaks of multidrug-resistant tuberculosis have focused international attention on the emergence of Mycobacterium tuberculosis strains that are resistant to antimycobacterial agents. Knowledge of the antimycobacterial resistance genetics and progress in molecular methods has made it possible to develop rapid molecular methods for susceptibility testing. This review presents the genetic background of drug resistance and introduces some methods for genotypic susceptibility testing.
Jalava
Jari
J
National Public Health Institute, Department of Human Microbial Ecology and Inflammation, Turku University Central Hospital, Turku, Finland. jari.jalava@ktl.fi
Marttila
Harri
H
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005838:Genotype; D006801:Humans; D055231:Lincosamides; D018942:Macrolides / Q000494:pharmacology; D008967:Molecular Biology / Q000379:methods*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D025361:Streptogramins / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D017931:DNA Primers; D055231:Lincosamides; D018942:Macrolides; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D025361:Streptogramins