TY - JOUR
T1 - Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid-rich dormancy conditions
AU - Aguilar-Ayala, Diana Angelica
AU - Cnockaert, Margo
AU - Vandamme, Peter
AU - Palomino, Juan Carlos
AU - Martin, Anandi
AU - Gonzalez-Y-Merchand, Jorge
N1 - Publisher Copyright:
© 2018 The Authors.
PY - 2018/3
Y1 - 2018/3
N2 - Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations – rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXFAMK- MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) – in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
AB - Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations – rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXFAMK- MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) – in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
KW - Dormancy model
KW - Dormant mycobacteria
KW - Drug susceptibility testing
KW - Drug-tolerant mycobacteria
KW - Lipids as carbon source
KW - Treatment failures and relapses
UR - http://www.scopus.com/inward/record.url?scp=85043402956&partnerID=8YFLogxK
U2 - 10.1099/jmm.0.000681
DO - 10.1099/jmm.0.000681
M3 - Artículo
C2 - 29458544
SN - 0022-2615
VL - 67
SP - 282
EP - 285
JO - Journal of Medical Microbiology
JF - Journal of Medical Microbiology
IS - 3
M1 - 000681
ER -