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2.
J Infect Dis ; 222(5): 871-879, 2020 08 04.
Article in English | MEDLINE | ID: mdl-32421167

ABSTRACT

A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.


Subject(s)
Acinetobacter Infections/enzymology , Acinetobacter baumannii/enzymology , Acinetobacter baumannii/growth & development , RNA Stability , RNA, Bacterial , Virulence Factors , gamma-Glutamyltransferase/metabolism , Acinetobacter baumannii/genetics , Alveolar Epithelial Cells/pathology , Animals , Cell Wall/pathology , Colony Count, Microbial , Half-Life , Humans , Kidney Diseases/microbiology , Kidney Diseases/pathology , Mice, Inbred BALB C , Moths , RNA, Messenger , gamma-Glutamyltransferase/genetics
3.
J Glob Antimicrob Resist ; 19: 210-215, 2019 12.
Article in English | MEDLINE | ID: mdl-31382074

ABSTRACT

OBJECTIVES: The aim of this study was to perform an epidemiological surveillance of multidrug-resistant (MDR) Acinetobacter baumannii genetic lineages among cancer patients in Egypt using the PCR-based open reading frame typing (POT) method. METHODS: A total of 160 MDR A. baumannii isolates were collected between January 2015 and December 2017 at a tertiary-care centre in Egypt. VITEK®2 system was used for preliminary species identification and antimicrobial susceptibility testing. The POT method was applied for confirmation of species identification and molecular epidemiological typing of the isolates. RESULTS: MDR A. baumannii isolates were classified into 15 POT types, including POT 122 (n=69), POT 69 (n=22) and other miscellaneous POT types (MPOTs) including POT 0, 8, 10, 12, 14, 40, 44, 52, 56, 93, 104, 106 and 108 (n=69). POT 122 isolates infected or colonised 61% of patients hospitalised in surgical wards and 54% of patients diagnosed with solid tumours and 51% were adults; whereas MPOT isolates infected or colonised 51% of patients hospitalised in paediatric wards and 49% of patients diagnosed with haematological malignancies and 51% were paediatric patients (P=0.007, 0.001 and 0.004, respectively). MPOT isolates were recovered from 46% of the collected blood specimens, whilst POT 122 isolates were recovered from 61% of the collected respiratory specimens (P=0.05). CONCLUSION: The current study demonstrates that the easy, low-cost POT method is convenient for rapid delineation of A. baumannii clonal diversity in a tertiary-care hospital in Egypt.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Neoplasms/microbiology , Acinetobacter Infections/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , DNA, Bacterial/genetics , Egypt/epidemiology , Female , Genotyping Techniques , Humans , Infant , Male , Microbial Sensitivity Tests , Middle Aged , Multiplex Polymerase Chain Reaction , Neoplasms/epidemiology , Open Reading Frames , Tertiary Care Centers/statistics & numerical data , Young Adult
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