title: Effects of two novel amino acid substitutions on the penicillin binding properties of the PBP5 C‑terminal from Enterococcus faecium.
abstract: The low‑affinity penicillin‑binding protein (PBP)5 is responsible for resistance to β‑lactam antibiotics in Enterococcus faecium. (E. faecium). In order to evaluate more fully the potential of this species for the development of resistance to β-lactam antibiotics, the present study aimed to examine the extent of penicillin-binding protein (PBP) variations in a collection of clinical E. faecium isolates. In the present study, the C‑terminal domain of PBP5 (PBP5‑CD) of 13 penicillin‑resistant clinical isolates of E. faecium were sequenced and the correlation between penicillin resistance and particular amino acid changes were analyzed. The present study identified for the first time, to the best of our knowledge, two novel substitutions (Tyr460Phe and Ala462Thr or Val462Thr) of E. faecium PBP5‑CD. The covalent interaction between penicillin and PBP5‑CD was also investigated using homology modeling and molecular docking methods. The theoretical calculation revealed that Phe460 and Thr462 were involved in penicillin binding, suggesting that substitutions at these positions exert effects on the affinity for penicillin, and this increased affinity translates into lower resistance in vitro.
authors.affiliation: Department of Medical and Cell Biology, Baotou Medical College, Baotou 014010, P.R. China.
authors.forename: Chengjiang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital, Baotou Medical College, Baotou 014010, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Niu
authors.affiliation: Clinical Laboratory, The Second Affiliated Hospital, Baotou Medical College, Baotou 014010, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medical and Cell Biology, Baotou Medical College, Baotou 014010, P.R. China.
authors.forename: Lishe
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital, Baotou Medical College, Baotou 014010, P.R. China.
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D016984:Enterococcus faecium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010406:Penicillins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins