A multidrug-resistant, acr1-deficient clinical isolate of Mycobacterium tuberculosis is unimpaired for replication in macrophages

Juliano Timm, Natalia Kurepina, Barry N. Kreiswirth, Frank A. Post, Gabrielle B. Walther, Helen C. Wainwright, Linda Gail Bekker, Gilla Kaplan, John D. McKinney

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1703-1710
Number of pages8
JournalJournal of Infectious Diseases
Volume193
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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