Corynebacterium glutamicum exhibits a membrane-related response to a small ferrocene-conjugated antimicrobial peptide.
Multiresistant bacteria are becoming more and more widespread. It is therefore necessary to have new compound groups in hand, such as small cationic peptides, to cope with these challenges. In this work, we present a comprehensive approach by monitoring protein expression profiles in a gram-positive bacterium (Corynebacterium glutamicum) to investigate the cellular response to such a compound, a ferrocene-conjugated arginine- and tryptophan-rich pentapeptide. To achieve this, a proteomic outline was performed where the compound-treated sample was compared with an untreated control. This study comprises more than 900 protein identifications, including numerous integral membrane proteins, and among these 185 differential expressions. Surprisingly, unregulated catalase and no elevated H(2)O(2) levels demonstrate that no oxidative stress occurs after treatment with the iron-containing compound as a consequence of the potential Fenton reaction. A sufficient iron supply is evidenced by the iron-containing protein aconitase and SufB (the latter belongs to an iron-sulfur cluster assembly system) and decreased levels of ATP-binding-cassette-type cobalamin/Fe(3+) siderophore transporters. The organometallic peptide antibiotic targets the cell membrane, which is evident by decreased levels of various integral membrane proteins, such as peptide permeases and transporters, and an altered lipid composition. Conversion to a more rigid cell membrane seems to be a relevant protective strategy of C. glutamicum against the ferrocene-conjugated antimicrobial peptide compound.
Fränzel
Benjamin
B
Lehrstuhl für Analytische Chemie, Biomolekulare Massenspektrometrie, Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitaetsstr. 150, 44780, Bochum, Germany.
Frese
Christian
C
Penkova
Maya
M
Metzler-Nolte
Nils
N
Bandow
Julia E
JE
Wolters
Dirk Andreas
DA
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D048230:Corynebacterium glutamicum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000075163:Metallocenes; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040901:Proteomics; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D010455:Peptides; C004998:ferrocene