TY - JOUR
T1 - A multidrug-resistant, acr1-deficient clinical isolate of Mycobacterium tuberculosis is unimpaired for replication in macrophages
AU - Timm, Juliano
AU - Kurepina, Natalia
AU - Kreiswirth, Barry N.
AU - Post, Frank A.
AU - Walther, Gabrielle B.
AU - Wainwright, Helen C.
AU - Bekker, Linda Gail
AU - Kaplan, Gilla
AU - McKinney, John D.
N1 - Funding Information:
Received 30 December 2005; accepted 3 February 2006; electronically published 11 May 2006. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grants AI051702 and AI054388 to J.D.M. and G.K., respectively). a Present affiliation: Department of HIV/GUM, King’s College, London, United Kingdom. b G.K. and J.D.M. contributed equally to this work. Reprints or correspondence: Dr. John D. McKinney, Laboratory of Infection Biology, The Rockefeller University, 1230 York Ave., New York, NY 10021 (mckinney@rockefeller.edu); or, Dr. Juliano Timm, Laboratory of Infection Biology, The Rockefeller University, 1230 York Ave., New York, NY 10021 (timmj@ rockefeller.edu).
PY - 2006/6/15
Y1 - 2006/6/15
N2 - Multidrug-resistant tuberculosis (MDR-TB) poses a serious threat to global public health. The mutations responsible for drug resistance in Mycobacterium tuberculosis have been identified, but what impact these mutations have on bacterial fitness is controversial. We analyzed 3 MDR strains of M. tuberculosis obtained from human immunodeficiency virus-negative patients with chronic pulmonary TB. One of these strains harbored a chromosomal deletion encompassing 15 open reading frames. Genes deleted in this strain included acr1, which encodes the virulence factor α-crystallin (Acr) 1, a protein that has been reported to be essential for M. tuberculosis replication in macrophages. We found that all 3 MDR isolates, including the acr1-deficient strain, replicated in cultured murine and human macrophages with the same kinetics as H37Rv, a virulent laboratory strain. These observations challenge the prevailing view that MDR bacteria are less fit than drug-susceptible bacteria and indicate that Acr1 is dispensable for bacterial growth in the human lung.
AB - Multidrug-resistant tuberculosis (MDR-TB) poses a serious threat to global public health. The mutations responsible for drug resistance in Mycobacterium tuberculosis have been identified, but what impact these mutations have on bacterial fitness is controversial. We analyzed 3 MDR strains of M. tuberculosis obtained from human immunodeficiency virus-negative patients with chronic pulmonary TB. One of these strains harbored a chromosomal deletion encompassing 15 open reading frames. Genes deleted in this strain included acr1, which encodes the virulence factor α-crystallin (Acr) 1, a protein that has been reported to be essential for M. tuberculosis replication in macrophages. We found that all 3 MDR isolates, including the acr1-deficient strain, replicated in cultured murine and human macrophages with the same kinetics as H37Rv, a virulent laboratory strain. These observations challenge the prevailing view that MDR bacteria are less fit than drug-susceptible bacteria and indicate that Acr1 is dispensable for bacterial growth in the human lung.
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U2 - 10.1086/504526
DO - 10.1086/504526
M3 - Article
C2 - 16703514
AN - SCOPUS:33744825969
VL - 193
SP - 1703
EP - 1710
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 12
ER -