title: In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species.
abstract: The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics.
authors.affiliation: Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.|InfectoGnostics Research Campus, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
authors.affiliation: InfectoGnostics Research Campus, Jena, Germany.|Alere Technologies GmbH, Jena, Germany.
authors.forename: Sascha D
authors.initials: SD
authors.lastname: Braun
authors.affiliation: Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.|InfectoGnostics Research Campus, Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stein
authors.affiliation: InfectoGnostics Research Campus, Jena, Germany.|Alere Technologies GmbH, Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Slickers
authors.affiliation: InfectoGnostics Research Campus, Jena, Germany.|Alere Technologies GmbH, Jena, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Ehricht
authors.affiliation: Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.|InfectoGnostics Research Campus, Jena, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Pletz
authors.affiliation: Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.|InfectoGnostics Research Campus, Jena, Germany.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Makarewicz
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016208:Databases, Factual; D004783:Environmental Microbiology; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000472:pathogenicity; D020539:Sequence Analysis, Protein; D012694:Serine / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D001618:beta-Lactamases / Q000032:analysis* / Q000737:chemistry / Q000235:genetics
chemical_list: D012694:Serine; D001618:beta-Lactamases