title: Vancomycin-resistant Leuconostoc mesenteroides and Lactobacillus casei synthesize cytoplasmic peptidoglycan precursors that terminate in lactate.
abstract: The emergence of acquired high-level resistance among Enterococcus species has renewed interest in mechanisms of resistance to glycopeptide antibiotics in gram-positive bacteria. In Enterococcus faecalis and Enterococcus faecium, resistance is encoded by the van gene cluster and is due to the production of a peptidoglycan precursor terminating in D-alanyl-D-lactate, to which vancomycin does not bind. Most Leuconostoc and many Lactobacillus species are intrinsically resistant to high levels of glycopeptide antibiotics, but the mechanism of resistance has not been elucidated. To determine whether the mechanisms of resistance are similar in intrinsically resistant bacteria, cytoplasmic peptidoglycan precursors were isolated from Leuconostoc mesenteroides and Lactobacillus casei and analyzed by mass spectrometry, revealing structures consistent with UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-(L-Ala)-D-Ala-D-lactate and UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, respectively.
authors.affiliation: Laboratory of Microbiology, Rockefeller University, New York, New York 10021.
authors.forename: S
authors.initials: S
authors.lastname: Handwerger
authors.forename: M J
authors.initials: MJ
authors.lastname: Pucci
authors.forename: K J
authors.initials: KJ
authors.lastname: Volk
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D004352:Drug Resistance, Microbial; D007773:Lactates / Q000378:metabolism*; D007780:Lacticaseibacillus casei / Q000187:drug effects / Q000378:metabolism*; D007934:Leuconostoc / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000737:chemistry; D014640:Vancomycin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D007773:Lactates; D010457:Peptidoglycan; D011498:Protein Precursors; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C076611:UDP-N-acetylmuramyl-Ala-Glu-Lys-Ala-lactate; C002225:UDP-N-acetylmuramic acid pentapeptide; D014640:Vancomycin