ABSTRACT
Aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methylases (16S RMTase) are two main resistance mechanisms against aminoglycosides. This study aimed to evaluate the frequency of AMEs and 16S rRNA methylase genes among aminoglycoside non-susceptible Acinetobacter baumannii isolates and to assess their clonal relationship using repetitive extragenic palindromic-PCR (rep-PCR). In this cross-sectional study, a total of 192 A. baumannii isolates were collected from the patients hospitalized in Qazvin, Iran (January 2016 to January 2018). Identification of isolates was performed by standard laboratory methods and API 20E strips. Antimicrobial susceptibility was determined by Kirby-Bauer method followed by examination of the genes encoding the AMEs and 16S RMTase by PCR and sequencing methods. The clonal relationship of isolates was carried out by rep-PCR. In total, 98.4% of isolates were non-susceptible to aminoglycosides, 98.4%, 97.9% and 83.9% of isolates were found to be non-susceptible against gentamicin, tobramycin and amikacin, respectively. The frequencies of aph(3')-VI, aac(6')-Ib, aac(3)-II, aph(3')-Ia and armA genes were 59.3%, 39.2%, 39.2%, 31.7% and 69.8%, respectively, either alone or in combination. Rep-PCR results showed that the aminoglycoside non-susceptible isolates belonged to three distinct clones: A (79.4%), B (17.5%) and C (3.2%). The findings of this study showed a high frequency for AMEs with the emergence of armA genes among the aminoglycoside non-susceptible A. baumannii isolates. Rational administration of aminoglycosides as well as using an appropriate infection control policy may reduce the presence of resistance to antibiotics in medical centres.
ABSTRACT
Gaucher disease, the most common of the sphingolipidoses, results from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45). Although type 2 (acute neuronopathic) Gaucher disease is associated with rapidly progressive and fatal neurologic deterioration, the pathophysiologic mechanisms leading to the neurologic symptoms and early demise remain uncharacterized. While the pathology encountered in Gaucher disease has been attributed to glucocerebroside storage, glucosylsphingosine (Glc-sph), a cytotoxic compound, also accumulates in the tissues. Elevations of brain Glc-sph have been reported in patients with types 2 and 3 Gaucher disease. In this study, Glc-sph levels were measured using HPLC in tissues from mice with type 2 Gaucher disease created with a null glucocerebrosidase allele. Compared with unaffected littermates, homozygous mice with type 2 Gaucher disease had approximately a 100-fold elevation of Glc-sph in brain, as well as elevated levels in other tissues. This accumulation was detected in utero by E 13 and increased progressively throughout gestation. Similarly, elevated Glc-sph levels were seen in human fetuses with type 2 Gaucher disease, indicating that therapy initiated after birth may be too late to prevent the sequelae of progressive neurologic damage that begins early in gestation. These findings suggest that the accumulation of Glc-sph may be responsible for the rapid demise of mice with type 2 Gaucher disease and the devastating clinical course seen in patients with type 2 Gaucher disease.
