Role of the Escherichia coli SbmA in the antimicrobial activity of proline-rich peptides.
In contrast to many antimicrobial peptides, members of the proline-rich group of antimicrobial peptides inactivate Gram-negative bacteria by a non-lytic mechanism. Several lines of evidence indicate that they are internalized into bacteria and their activity mediated by interaction with unknown cellular components. With the aim of identifying such interactors, we selected mutagenized Escherichia coli clones resistant to the proline-rich Bac7(1-35) peptide and analysed genes responsible for conferring resistance, whose products may thus be involved in the peptide's mode of action. We isolated a number of genomic regions bearing such genes, and one in particular coding for SbmA, an inner membrane protein predicted to be part of an ABC transporter. An E. coli strain carrying a point mutation in sbmA, as well as other sbmA-null mutants, in fact showed resistance to several proline-rich peptides but not to representative membranolytic peptides. Use of fluorescently labelled Bac7(1-35) confirmed that resistance correlated with a decreased ability to internalize the peptide, suggesting that a bacterial protein, SbmA, is necessary for the transport of, and for susceptibility to, proline-rich antimicrobial peptides of eukaryotic origin.
Mattiuzzo
Maura
M
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
Bandiera
Antonella
A
Gennaro
Renato
R
Benincasa
Monica
M
Pacor
Sabrina
S
Antcheva
Nikolinka
N
Scocchi
Marco
M
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
D018528:ATP-Binding Cassette Transporters; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C481640:Bac7(1-35) peptide; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins