Prevalence and molecular mechanisms of colistin resistance in Acinetobacter baumannii clinical isolates in Tehran, Iran

Colistin is one of the last remaining active antibiotics against multidrug resistant Gram-negative bacteria. However, several recent studies reported colistin-resistant (ColR) Acinetobacter baumannii from different countries. In the current study, we investigated molecular mechanisms involved in colistin resistance in A. baumannii isolates from different clinical samples. A total of 110 clinical A. baumannii isolates were collected from two hospitals in Tehran. Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to the Clinical and Laboratory Standards Institute. For the ColR isolates, mutation was detected in pmrA, pmrB, lpxA, lpxC, and lpxD genes using the polymerase chain reaction (PCR) and sequencing. Moreover, the relative expression of the pmrC gene was calculated using quantitative reverse transcription PCR. Three colistin resistant isolates were identified with MIC between 8 and 16 mg/mL and were resistant to all the tested antimicrobial agents. All the three isolates had a mutation in the pmrB, pmrA, lpxA, lpxD, and lpxC genes. Moreover, the overexpression of pmrC gene was observed in all isolates. Our results showed that the upregulation of the PmrAB two component system was the primary mechanism linked to colistin resistance among the studied colistin resistant A. baumannii isolates

Minocycline attenuates depressive-like behaviors in mice treated with the low dose of intracerebroventricular streptozotocin; the role of mitochondrial function and neuroinflammation

Neuroinflammation and mitochondrial dysfunction are suggested as mechanisms which are implicated in the pathophysiology of depression. Streptozotocin (STZ) is known to produce immune-inflammatory responses and mitochondrial dysfunction in different types of animal models of disease (e.g. type-1 diabetes and Alzheimer’s disease). Therefore, a single low dose of Streptozotocin (STZ; intracerebroventricular, i.c.v, 0.2 mg/mouse) was used to induce an animal model of depression. The present study aims to investigate the effects of short (24 h) and long (14 days) exposure to minocycline on STZ-induced depressive-like behaviors (n = 6–8), hippocampal oxidative state biomarkers (n = 4), and the expression of hippocampal genes related to innate immunity (n = 3) in the hippocampus of male adult mice. In addition, the protective effects of different modes of minocycline (acute pretreatment (20 mg/kg, 1 h before STZ), acute post-treatment (20 mg/kg, 24 h after STZ), chronic pretreatment (5 mg/kg/day for 14 days before STZ), and chronic post-treatment (5 mg/kg/day for 14 days after STZ) were compared with the STZ effects. As the data showed, both short and long effects of STZ were associated with the depressive-like behaviors, abnormal mitochondrial function, and upregulation of neuroinflammatory genes in the hippocampus. Different modes of minocycline treatment could attenuate the negative impact of STZ on animals. The data suggested that minocycline at a human therapeutic dose (5 mg/kg) had protective effects against acute cellular damage induced by oxidation and the consequent inflammatory response