99mTc-Labeled, Colistin Encapsulated, Theranostic Liposomes for Pseudomonas aeruginosa Infection.

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with 99mTc, colistin encapsulated, neutral and cationic liposome formulations were prepared as the theranostic agent for Pseudomonas aeruginosa infections. Liposomes exhibited appropriate physicochemical properties thanks to their nano-particle size (between 173 and 217 nm), neutral zeta potential value (about - 6.5 and 2.8 mV), as well as encapsulation efficiency of about 75%. All liposome formulations were radiolabeled with over 90% efficiency, and the concentration of stannous chloride was found as 1 mg.mL-1 to obtain maximum radiolabeling efficiency. In alamar blue analysis, neutral liposome formulations were found more biocompatible compared with the cationic formulations. Neutral colistin encapsulated liposomes were found to be more effective against P. aeruginosa strain according to their time-dependent antibacterial effect, in addition to their highest bacterial binding capacity. As conclusion, theranostic, nanosized, colistin encapsulated, neutral liposome formulations were found as promising agents for the imaging and treating of P. aeruginosa infections.

Iron in infectious diseases friend or foe?: The role of gut microbiota.

Iron is a trace element involved in metabolic functions for all organisms, from microorganisms to mammalians. Iron deficiency is a prevalent health problem that affects billions of people worldwide, and iron overload could have some hazardous effect. The complex microbial community in the human body, also called microbiota, influences the host immune defence against infections. An imbalance in gut microbiota, dysbiosis, changes the host's susceptibility to infections by regulating the immune system. In recent years, the number of studies on the relationship between infectious diseases and microbiota has increased. Gut microbiota is affected by different parameters, including mode of delivery, hygiene habits, diet, drugs, and plasma iron levels during the lifetime. Gut microbiota may influence iron levels in the body, and iron overload and deficiency can also affect gut microbiota composition. Novel researches on microbiota shed light on the fact that the bidirectional interactions between gut microbiota and iron play a role in the pathogenesis of many diseases, especially infections. A better understanding of these interactions may help us to comprehend the pathogenesis of many infectious and metabolic diseases affecting people worldwide and following the development of more effective preventive and/or therapeutic strategies. In this review, we aimed to present the iron-mediated host-gut microbiota interactions, susceptibility to bacterial infections, and iron-targeted therapy approaches for infections.

Investigating Biofilm Formation and Antibiofilm Activity Using Real Time Cell Analysis Method in Carbapenem Resistant Acinetobacter baumannii Strains.

Acinetobacter baumannii is a significant nosocomial pathogen, with its biofilm forming capacity playing an important role in its pathogenicity. The fast and reliable detection of the biofilm formation and measurement of antibiofilm activity of various molecules are critical for combating A. baumannii infections. In this study, we aimed to detect biofilm formation by real time cell analyses (RTCA) method in clinical A. baumannii isolates and to investigate antibiofilm activities of tigecycline (TGC), N-acetylcysteine (NAC), and acetylsalicylic acid (ASA). The effect of the tested drugs on expressions of biofilm-related genes bap and csuE in clinical A. baumannii strains was also analyzed by real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Biofilm forming capacities for strong and weak biofilm producer A. baumannii strains were detected within 10 h by RTCA method (P < 0.05). We also observed that sub-minimum inhibitory concentrations of NAC + TGC and ASA + TGC combinations could significantly reduce biofilm formation and expression of biofilm-related genes in A. baumanii strains. No statistically significant activity of the tested drugs was detected against mature biofilms of the bacterial strains with the RTCA method. These results suggest that reproducible results on biofilm production capacity of A. baumannii strains and antibiofilm activities of various compounds can be obtained in a short time using RTCA method. Therefore, RTCA method seems to be a beneficial technique for biofilm detection and can help in combating A. baumannii infections by giving health providers the opportunity of implementing antibiofilm treatment strategies in a timely manner.

Antifungal and Antibiofilm Activities of Selective Serotonin Reuptake Inhibitors Alone and in Combination with Fluconazole.

OBJECTIVES: Candida spp. are clinically important pathogens that cause difficulties for treatment by biofilm formation. Considering antifungal resistance rates and the limitations in the discovery of new antifungals, the antifungal and antibiofilm effects of various drugs used for different therapeutic purposes are becoming more important. The goal of our study was to determine the antifungal and antibiofilm effects of the selective serotonin reuptake inhibitors (SSRIs), namely sertraline (SRT), paroxetine (PRX), and fluoxetine (FLX) alone and in combination with fluconazole (FLC) against Candida spp. MATERIALS AND METHODS: Twenty Candida spp. strains isolated from clinical samples from Ege University Hospital were identified by the Dalmau method and matrix-assisted laser desorption ionization time of flight mass spectrometry. The minimum inhibitory concentrations (MICs) of the SSRIs and FLC were detected by broth microdilution method. Synergistic interactions between the SSRIs and FLC were investigated by checkerboard assay. The antibiofilm effects of the SSRIs were determined by spectrophotometric microplate method. RESULTS: Among the isolates, five different Candida spp. (C. albicans, C. glabrata, C. krusei, C. tropicalis, and C.parapsilosis) were identified. The MICs of the SSRIs ranged between 16-512 µg/mL. While SRT showed the highest antifungal effect, the antibiofilm efficacy of FLX was higher than that of the other agents. Moreover, FLX and PRX showed a synergistic effect with FLC in 13 and 19 isolates, respectively. Four isolates were strong biofilm producers while nine isolates were moderate biofilm producers. C. parapsilosis strains showed higher biofilm production than the other species. At MIC/2 concentration, FLX and SRT alone inhibited mature biofilms in six and five isolates, respectively, while PRX caused increases biofilm formation in seven isolates. CONCLUSION: This study revealed that MIC/2 concentrations of SSRIs could have antifungal and antibiofilm effects. SRT and FLX alone or in combination with antifungals may possibly have therapeutic potential for combating fungal infections.