Design, synthesis, and antimicrobial evaluation of a novel bone-targeting bisphosphonate-ciprofloxacin conjugate for the treatment of osteomyelitis biofilms

Osteomyelitis is a major problem worldwide and is devastating due to the potential for limb-threatening sequelae and mortality. Osteomyelitis pathogens are bone-attached biofilms, making antibiotic delivery challenging. Here we describe a novel osteoadsorptive bisphosphonate-ciprofloxacin conjugate (BV600022), utilizing a “target and release” chemical strategy, which demonstrated a significantly enhanced therapeutic index versus ciprofloxacin for the treatment of osteomyelitis in vivo. In vitro antimicrobial susceptibility testing of the conjugate against common osteomyelitis pathogens revealed an effective bactericidal profile and sustained release of the parent antibiotic over time. Efficacy and safety were demonstrated in an animal model of periprosthetic osteomyelitis, where a single dose of 10 mg/kg (15.6 μmol/kg) conjugate reduced the bacterial load by 99% and demonstrated nearly an order of magnitude greater activity than the parent antibiotic ciprofloxacin (30 mg/kg, 90.6 μmol/kg) given in multiple doses. Conjugates incorporating a bisphosphonate and an antibiotic for bone-targeted delivery to treat osteomyelitis biofilm pathogens constitute a promising approach to providing high bone-antimicrobial potency while minimizing systemic exposure

The Phylogenetic Structure of Reptile, Avian and Uropathogenic Escherichia coli with Particular Reference to Extraintestinal Pathotypes

The impact of the Gram-negative bacterium Escherichia coli (E. coli) on the microbiomic and pathogenic phenomena occurring in humans and other warm-blooded animals is relatively well-recognized. At the same time, there are scant data concerning the role of E. coli strains in the health and disease of cold-blooded animals. It is presently known that reptiles are common asymptomatic carriers of another human pathogen, Salmonella, which, when transferred to humans, may cause a disease referred to as reptile-associated salmonellosis (RAS). We therefore hypothesized that reptiles may also be carriers of specific E. coli strains (reptilian Escherichia coli, RepEC) which may differ in their genetic composition from the human uropathogenic strain (UPEC) and avian pathogenic E. coli (APEC). Therefore, we isolated RepECs (n = 24) from reptile feces and compared isolated strains’ pathogenic potentials and phylogenic relations with the aforementioned UPEC (n = 24) and APEC (n = 24) strains. To this end, we conducted an array of molecular analyses, including determination of the phylogenetic groups of E. coli, virulence genotyping, Pulsed-Field Gel Electrophoresis-Restriction Analysis (RA-PFGE) and genetic population structure analysis using Multi-Locus Sequence Typing (MLST). The majority of the tested RepEC strains belonged to nonpathogenic phylogroups, with an important exception of one strain, which belonged to the pathogenic group B2, typical of extraintestinal pathogenic E. coli. This strain was part of the globally disseminated ST131 lineage. Unlike RepEC strains and in line with previous studies, a high percentage of UPEC strains belonged to the phylogroup B2, and the percentage distribution of phylogroups among the tested APEC strains was relatively homogenous, with most coming from the following nonpathogenic groups: C, A and B1. The RA-PFGE displayed a high genetic diversity among all the tested E. coli groups. In the case of RepEC strains, the frequency of occurrence of virulence genes (VGs) was lower than in the UPEC and APEC strains. The presented study is one of the first attempting to compare the phylogenetic structures of E. coli populations isolated from three groups of vertebrates: reptiles, birds and mammals (humans).</jats:p

Biochemical and cellular properties of Gluconacetobacter xylinus cultures exposed to different modes of rotating magnetic field

The aim of the present study was to evaluate the impact of a rotating magnetic field (RMF) on cellular and biochemical properties of Gluconacetobacter xylinus during the process of cellulose synthesis by these bacteria. The application of the RMF during bacterial cellulose (BC) production intensified the biochemical processes in G. xylinus as compared to the RMF-unexposed cultures. Moreover, the RMF had a positive impact on the growth of cellulose-producing bacteria. Furthermore, the application of RMF did not increase the number of mutants unable to produce cellulose. In terms of BC production effi cacy, the most favorable properties were found in the setting where RMF generator was switched off for the fi rst 72 h of cultivation and switched on for the further 72 h. The results obtained can be used in subsequent studies concerning the optimization of BC production using different types of magnetic fields including RMF, especially

High-strength cellulose nanofibers produced via swelling pretreatment based on a choline chloride–imidazole deep eutectic solvent

Abstract A deep eutectic solvent (DES) based on choline chloride and imidazole (CCIMI) was investigated for swelling of cellulose fibers prior to mechanical disintegration into cellulose nanofibers (CNFs). The dimensions of the DES treated and washed fibers were investigated after various treatment conditions (time, temperature, and cellulose consistency) using DES based on choline chloride–urea (CCUrea) and pure imidazole as references. Even mild treatment conditions (15 minutes at 60 °C) with CCIMI increased the diameter of the fibers from 18.1 to 18.9 μm, and a maximum diameter of 19.9 μm was obtained after three hours at 100 °C. Overall, CCIMI resulted in a higher degree of swelling compared to both references. In addition, pure imidazole caused a decrease in the degree of polymerization of cellulose, whereas cellulose degradation in CCIMI was negligible. The mechanical disintegration of CCIMI-treated fibers resulted in the production of CNF films with very good mechanical properties—specific tensile strength and work capacity being over 200 kNm kg−1 and 10 kJ kg−1, respectively—whereas CNFs films produced using choline chloride–urea had notably lower values (182 kNM kg−1 and 7 kJ kg−1, respectively). In addition, CNF films exhibited good oxygen barrier properties, even at an elevated relative humidity level (80%). CCIMI could be recycled without any effect on the mechanical properties of CNF films. The results presented here indicate CCIMI is a highly efficient pretreatment media for swelling and further nanofibrillation of cellulose, even at mild treatment conditions

Impedance Sensors Made in PCB and LTCC Technologies for Monitoring Growth and Degradation of Pseudomonal Biofilm

The suitability of low-cost impedance sensors for microbiological purposes and biofilm growth monitoring was evaluated. The sensors with interdigitated electrodes were fabricated in PCB and LTCC technologies. The electrodes were golden (LTCC) or gold-plated (PCB) to provide surface stability. The sensors were used for monitoring growth and degradation of the reference ATCC 15442 Pseudomonas aeruginosa strain biofilm in invitro setting. During the experiment, the impedance spectra of the sensors were measured and analysed using electrical equivalent circuit (EEC) modelling. Additionally, the process of adhesion and growth of bacteria on a sensor’s surface was assessed by means of the optical and SEM microscopy. EEC and SEM microscopic analysis revealed that the gold layer on copper electrodes was not tight, making the PCB sensors susceptible to corrosion while the LTCC sensors had good surface stability. It turned out that the LTCC sensors are suitable for monitoring pseudomonal biofilm and the PCB sensors are good detectors of ongoing stages of biofilm formation