Internalization of a thiazole-modified peptide in Sinorhizobium meliloti occurs by BacA-dependent and -independent mechanisms.
BacA proteins play key roles in the chronic intracellular infections of Sinorhizobium meliloti, Brucella abortus and Mycobacterium tuberculosis within their respective hosts. S. meliloti, B. abortus and M. tuberculosis BacA-deficient mutants have increased resistance to the thiazole-modified peptide bleomycin. BacA has been previously hypothesized, but not experimentally verified, to be involved in bleomycin uptake. In this paper, we show that a BacA-dependent mechanism is the major route of bleomycin internalization in S. meliloti. We also determined that the B. abortus and S. meliloti BacA proteins are functional homologues and that the B. abortus BacA protein is involved in the uptake of both bleomycin and proline-rich peptides. Our findings also provide evidence that there is a second, BacA-independent minor mechanism for bleomycin internalization in S. meliloti. We determined that the BacA-dependent and -independent mechanisms of bleomycin uptake are energy-dependent, consistent with both mechanisms of bleomycin uptake involving transport systems.
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Silvia
S
Wehmeier
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Markus F F
MFF
Arnold
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Victoria L
VL
Marlow
Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, 5415, Boul. de l'Assomption, Montreal, QC H1T 2M4, Canada.
Mustapha
M
Aouida
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Kamila K
KK
Myka
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Vivien
V
Fletcher
Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
Monica
M
Benincasa
Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
Marco
M
Scocchi
Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, 5415, Boul. de l'Assomption, Montreal, QC H1T 2M4, Canada.
Dindial
D
Ramotar
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Gail P
GP
Ferguson
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D001761:Bleomycin / Q000378:metabolism; D016962:Sinorhizobium meliloti / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism*
D001426:Bacterial Proteins; D013844:Thiazoles; D001761:Bleomycin