Replication Rates of Mycobacterium tuberculosis in Human Macrophages Do Not Correlate with Mycobacterial Antibiotic Susceptibility
2014 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 11, e112426- p.Article in journal (Refereed) Published
The standard treatment of tuberculosis (TB) takes six to nine months to complete and this lengthy therapy contributes to the emergence of drug-resistant TB. TB is caused by Mycobacterium tuberculosis (Mtb) and the ability of this bacterium to switch to a dormant phenotype has been suggested to be responsible for the slow clearance during treatment. A recent study showed that the replication rate of a non-virulent mycobacterium, Mycobacterium smegmatis, did not correlate with antibiotic susceptibility. However, the question whether this observation also holds true for Mtb remains unanswered. Here, in order to mimic physiological conditions of TB infection, we established a protocol based on long-term infection of primary human macrophages, featuring Mtb replicating at different rates inside the cells. During conditions that restricted Mtb replication, the bacterial phenotype was associated with reduced acid-fastness. However, these phenotypically altered bacteria were as sensitive to isoniazid, pyrazinamide and ethambutol as intracellularly replicating Mtb. In support of the recent findings with M. smegmatis, we conclude that replication rates of Mtb do not correlate with antibiotic tolerance.
Place, publisher, year, edition, pages
Public Library of Science , 2014. Vol. 9, no 11, e112426- p.
Clinical Medicine Basic Medicine
IdentifiersURN: urn:nbn:se:liu:diva-113014DOI: 10.1371/journal.pone.0112426ISI: 000345250400061PubMedID: 25386849OAI: oai:DiVA.org:liu-113014DiVA: diva2:778974
Funding Agencies|Bill and Melinda Gates Foundation; Swedish Research Council [2009-3821, 2012-3349]; Swedish International Development Cooperation Agency; Swedish Heart-Lung Foundation; King Oscar II Foundation; Carl Trygger Foundation; Clas Groschinsky Foundation2015-01-122015-01-082015-04-01