title: Analysis of genes encoding penicillin-binding proteins in clinical isolates of Acinetobacter baumannii.
abstract: There is limited information on the role of penicillin-binding proteins (PBPs) in the resistance of Acinetobacter baumannii to β-lactams. This study presents an analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty-six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from three teaching hospitals in Spain were included. The antimicrobial susceptibility profile, clonal pattern, and genomic species identification were also evaluated. Based on the six complete genomes of A. baumannii, the PBP genes were identified, and primers were designed for each gene. The nucleotide sequences of the genes identified that encode PBPs and the corresponding amino acid sequences were compared with those of ATCC 17978. Seven PBP genes and one monofunctional transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular-mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7 (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot mutation regions were observed, although most of the allelic changes found translated into silent mutations. The amino acid consensus sequences corresponding to the PBP genes in the genomes and the clinical isolates were highly conserved. The changes found in amino acid sequences were associated with concrete clonal patterns but were not directly related to susceptibility or resistance to β-lactams. An insertion sequence disrupting the gene encoding PBP6b was identified in an endemic carbapenem-resistant clone in one of the participant hospitals.
authors.affiliation: Service of Microbiology, University Hospital Marqués de Valdecilla—IFIMAV, and Department of Molecular Biology, School of Medicine, University of Cantabria, Barcelona, Barcelona, Spain. rodrigocayosilva@gmail.com
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cayô
authors.forename: María-Cruz
authors.initials: MC
authors.lastname: Rodríguez
authors.forename: Paula
authors.initials: P
authors.lastname: Espinal
authors.forename: Felipe
authors.initials: F
authors.lastname: Fernández-Cuenca
authors.forename: Alain A
authors.initials: AA
authors.lastname: Ocampo-Sosa
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
authors.forename: Juan A
authors.initials: JA
authors.lastname: Ayala
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D006784:Hospitals, Teaching; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D013030:Spain; D018440:beta-Lactam Resistance / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D046915:Penicillin-Binding Proteins