Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America.
BACKGROUND
Mutations associated with resistance to rifampin or streptomycin have been reported for W/Beijing and Latin American Mediterranean (LAM) strain families of Mycobacterium tuberculosis. A few studies with limited sample sizes have separately evaluated mutations in katG, ahpC and inhA genes that are associated with isoniazid (INH) resistance. Increasing prevalence of INH resistance, especially in high tuberculosis (TB) prevalent countries is worsening the burden of TB control programs, since similar transmission rates are noted for INH susceptible and resistant M. tuberculosis strains.


RESULTS
We, therefore, conducted a comprehensive evaluation of INH resistant M. tuberculosis strains (n = 224) from three South American countries with high burden of drug resistant TB to characterize mutations in katG, ahpC and inhA gene loci and correlate with minimal inhibitory concentrations (MIC) levels and spoligotype strain family. Mutations in katG were observed in 181 (80.8%) of the isolates of which 178 (98.3%) was contributed by the katG S315T mutation. Additional mutations seen included oxyR-ahpC; inhA regulatory region and inhA structural gene. The S315T katG mutation was significantly more likely to be associated with MIC for INH >or=2 microg/mL. The S315T katG mutation was also more frequent in Haarlem family strains than LAM (n = 81) and T strain families.


CONCLUSIONS
Our data suggests that genetic screening for the S315T katG mutation may provide rapid information for anti-TB regimen selection, epidemiological monitoring of INH resistance and, possibly, to track transmission of INH resistant strains.
Dalla Costa
Elis R
ER
State Foundation for Production and Research in Health (FEPPS), Porto Alegre, Brazil. erdallacosta@yahoo.com.br
Ribeiro
Marta O
MO
Silva
Márcia S N
MS
Arnold
Liane S
LS
Rostirolla
Diana C
DC
Cafrune
Patricia I
PI
Espinoza
Roger C
RC
Palaci
Moises
M
Telles
Maria A
MA
Ritacco
Viviana
V
Suffys
Philip N
PN
Lopes
Maria L
ML
Campelo
Creuza L
CL
Miranda
Silvana S
SS
Kremer
Kristin
K
da Silva
Pedro E Almeida
PE
Fonseca
Leila de Souza
Lde S
Ho
John L
JL
Kritski
Afrânio L
AL
Rossetti
Maria L R
ML
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D013020:South America; D014376:Tuberculosis / Q000382:microbiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007538:Isoniazid