RT Journal Article
SR Electronic
T1 The antibiotic phazolicin displays a dual mode of uptake in Gram-negative bacteria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.27.489825
DO 10.1101/2022.04.27.489825
A1 Dmitrii Y. Travin
A1 Armelle Vigouroux
A1 Satomi Inaba-Inoue
A1 Feng Qu
A1 Romain Jouan
A1 Joy Lachat
A1 Dmitry Sutormin
A1 Svetlana Dubiley
A1 Konstantinos Beis
A1 Solange Moréra
A1 Konstantin Severinov
A1 Peter Mergaert
YR 2022
UL http://biorxiv.org/content/early/2022/04/29/2022.04.27.489825.abstract
AB Phazolicin (PHZ) is a peptide antibiotic exhibiting narrow-spectrum activity against rhizobia closely related to its producer Rhizobium sp. Pop5. Using genetic and biochemical techniques, we here identified BacA and YejABEF as two importers of PHZ in a sensitive model strain Sinorhizobium meliloti Sm1021. BacA and YejABEF are members of SLiPT and ABC transporter families of non-specific peptide importers, respectively. The uptake of PHZ by two distinct families of transporters dramatically decreases the naturally occurring rate of resistance. Moreover, since both BacA and YejABEF are essential for the development of functional symbiosis of rhizobia with leguminous plants, the acquisition of PHZ resistance via the inactivation of transporters is further disfavoured since single bacA or yejABEF mutants are unable to propagate in root nodules. Crystal structures of the periplasmic subunit YejA from S. meliloti and Escherichia coli revealed fortuitous bound peptides, suggesting a non-specific peptide-binding mechanism that facilitates the uptake of PHZ and other antimicrobial peptides.SIGNIFICANCE Many bacteria produce antimicrobial peptides to eliminate competitors and create an exclusive niche. These peptides kill bacteria by either membrane disruption or inhibiting essential intracellular processes. The Achilles heel of the latter type of antimicrobials is their dependence on transporters to enter the susceptible bacteria since mutations in such transporters result in resistance. We describe here how the ribosome-targeting peptide phazolicin, produced by Rhizobium sp. Pop5, uses two different transporters, BacA and YejABEF, to get into the cells of the symbiotic bacterium Sinorhizobium meliloti. This dramatically reduces the probability of resistance acquisition. Both transporters need to be inactivated for phazolicin resistance acquisition. Since these transporters are also crucial in S. meliloti for its symbiotic association with host plants, their inactivation in biological settings is highly unlikely. This makes PHZ an attractive lead for the development of a biocontrol agent with potential for use in agriculture.Competing Interest StatementThe authors have declared no competing interest.