Tripropeptins, Novel Antimicrobial Agents Produced by Lysobacter sp. I. Taxonomy, Isolation and Biological Activities.

Abstract

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Tripropeptin C Blocks the Lipid Cycle of Cell Wall Biosynthesis by Complex Formation with Undecaprenyl Pyrophosphate

“…Our experiments therefore revealed that TPPC exhibits potent activity against the drug-resistant pathogens MRSA and VRE both in vivo and in vitro. In our experiments, clinically isolated strains, including MRSA, VRE, and penicillin-resistant Streptococcus pneumoniae, showed no resistance to TPPC (4,5), indicating that TPPC has a unique mode of action.…”

“…TPPC was isolated by the method reported previously (4). VAN was purchased from Shionogi (Osaka, Japan).…”

“…TPPC consists of a cyclic octapeptide core and a fatty acyl side chain, 13-methyl-3-hydroxy-tetradecanoic acid ( Fig. 1) (4,6). TPPC has a characteristic structure in that five of the eight amino acid residues in the peptide core are unusual amino acids: D-allo-threonine, L-trans-3-hydroxy proline, threo-beta-hydroxy-L-aspartic acid, threo-beta-hydroxy-D-aspartic acid, and D-proline.…”

“…This class of antibiotics shows potent in vitro antimicrobial activity against Gram-positive pathogens, including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), and also shows excellent therapeutic efficacy, comparable to that of vancomycin (VAN), the last resort for MRSA treatment, in a mouse model of staphylococcal septicemia (11,22). TPPC shows no cross-resistance to other important antibiotic-resistant strains (4,5), strongly suggesting that TPPC has a unique mode of action. TPPC also exhibits a favorable toxicological profile that includes no acute toxicity and no 14-day repeated toxicities in mice when administered intravenously at 300 mg/kg of body weight and 100 mg/kg/day, respectively (7).…”

Volatile communication between fungi and bacteria

“…5A). Although the structure of tripropeptin A has been known for more than a decade (Hashizume et al, 2001, Hashizume et al, 2004, genetic analysis of its biosynthesis was only recently reported (Medema et al, 2014). Our study revealed that three NRPS genes trpA, trpB, trpC are organized in a single-operon (Fig.…”