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.
Wehmeier
Silvia
S
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Arnold
Markus F F
MFF
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Marlow
Victoria L
VL
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Aouida
Mustapha
M
Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, 5415, Boul. de l'Assomption, Montreal, QC H1T 2M4, Canada.
Myka
Kamila K
KK
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Fletcher
Vivien
V
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Benincasa
Monica
M
Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
Scocchi
Marco
M
Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
Ramotar
Dindial
D
Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, 5415, Boul. de l'Assomption, Montreal, QC H1T 2M4, Canada.
Ferguson
Gail P
GP
School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
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