Bacterial multi‐solute transporters

Abstract

Bacterial membrane proteins of the SbmA/BacA family are multi-solute transporters that mediate the uptake of structurally diverse hydrophilic molecules, including aminoglycoside antibiotics and antimicrobial peptides. Some family members are full-length ATP-binding cassette (ABC) transporters, whereas other members are truncated homologues that lack the nucleotidebinding domains and thus mediate ATP-independent transport. A recent cryo-EM structure of the ABC transporter Rv1819c from Mycobacterium tuberculosis has shed light on the structural basis for multi-solute transport and has provided insight into the mechanism of transport. Here, we discuss how the protein architecture makes SbmA/BacA family transporters prone to inadvertent import of antibiotics and speculate on the question which physiological processes may benefit from multi-solute transport.

The ATP-Binding Cassette (ABC) Transport Systems in Mycobacterium tuberculosis: Structure, Function, and Possible Targets for Therapeutics

“…Studies have shown that a mutant bacillus of rv1819c loses the ability to maintain chronic infection in murine models and increases resistance to bleomycin [82]. Besides the previous functions attributed to Rv1819c, it is also speculated to play a role in the transport of peptides and drugs [31].…”

Multidrug Resistance in Mammals and Fungi—From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms

“…Thus, we need atomic structures reflecting more than a single conformation and possibly many transition states [ 352 ], as well as extensive validation by biochemistry and genetics, to validate their biological relevance and define catalytic cycles. Furthermore, there is an unmet need for more interdisciplinary collaborations that also engage alternative structural approaches like NMR [ 353 , 354 , 355 , 356 ] as well as complementary biophysical methods [ 265 , 357 , 358 , 359 ] to expand our mechanistic views of ABC transporters in all living kingdoms.…”

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

“…In the case of OaBac5mini, the peptide appeared to kill E. coli using intracellular sites of action that were proposed to include protein and DNA synthesis 99,105 , which was supported by other studies 34,106 , although mechanisms used by the peptide to cross the inner membrane of the organism were not determined 99,105 . However, a close bovine homologue of OaBac5mini appeared to kill E. coli using nonmembranolytic mechanisms that involved internalization via SbmA [107][108][109] , an inner membrane transporter 110 , and the blocking of protein synthesis, facilitated by the homologue's extended, polyproline helical structure [107][108][109] . The use of Sbma and MdtM, which is also an inner membrane transporter 111 , facilitates the antibacterial action other proline-rich AMPs, and it has been suggested that OaBac5mini and OaBac7.5mini may use similar uptake mechanisms 34,104,112,113 .…”

“…The use of Sbma and MdtM, which is also an inner membrane transporter 111 , facilitates the antibacterial action other proline-rich AMPs, and it has been suggested that OaBac5mini and OaBac7.5mini may use similar uptake mechanisms 34,104,112,113 . Interestingly, Sbma is of unknown physiological function 110 , but MdtM is known to be an efflux pump that contributes to the intrinsic resistance of E. coli to drugs and antimicrobials by extruding these compounds from the cytoplasm 111,114 . This co-option of transporters involved in microbial defence mechanisms to facilitate the activity of AMPs against the host microbes has been reported in a number of other cases 34,35,104 and would seem to represent an adaptation strategy in the ongoing coevolution of microbial pathogens and their hosts 115 .…”