RESUMO
Bacteria express a plethora of efflux pumps that can transport structurally varied molecules, including antimicrobial agents and antibiotics, out of cells. Thus, efflux pump systems participate in lowering intracellular concentrations of antibiotics, which allows phenotypic multidrug-resistant (MDR) bacteria to survive effectively amid higher concentrations of antibiotics. Acinetobacter baumannii is one of the classic examples of pathogens that can carry multiple efflux pump systems, which allows these bacteria to be MDR-to-pan-drug resistant and is now considered a public health threat. Therefore, efflux pumps in A. baumannii have gained major attention worldwide, and there has been increased interest in studying their mechanism of action, substrates, and potential efflux pump inhibitors (EPIs). Efflux pump inhibitors are molecules that can inhibit efflux pumps, rendering pathogens susceptible to antimicrobial agents, and are thus considered potential therapeutic agents for use in conjunction with antibiotics. This review focuses on the types of various efflux pumps detected in A. baumannii, their molecular mechanisms of action, the substrates they transport, and the challenges in developing EPIs that can be clinically useful in reference to A. baumannii.
RESUMO
BACKGROUND: The occurrence of hyperplasia, through myofibre splitting, remains a widely debated phenomenon. Structural alterations and fibre typing of skeletal muscle fibres, as seen during regeneration and in certain muscle diseases, can be challenging to interpret. Neuromuscular electrical stimulation can induce myofibre necrosis followed by changes in spatial and temporal cellular processes. Thirty days following electrical stimulation, remnants of regeneration can be seen in the myofibre and its basement membrane as the presence of small myofibres and encroachment of sarcolemma and basement membrane (suggestive of myofibre branching/splitting). The purpose of this study was to investigate myofibre branching and fibre type in a systematic manner in human skeletal muscle undergoing adult regenerative myogenesis. METHODS: Electrical stimulation was used to induce myofibre necrosis to the vastus lateralis muscle of one leg in 5 young healthy males. Muscle tissue samples were collected from the stimulated leg 30 days later and from the control leg for comparison. Biopsies were sectioned and stained for dystrophin and laminin to label the sarcolemma and basement membrane, respectively, as well as ATPase, and antibodies against types I and II myosin, and embryonic and neonatal myosin. Myofibre branches were followed through 22 serial Sects. (264 µm). Single fibres and tissue blocks were examined by confocal and electron microscopy, respectively. RESULTS: Regular branching of small myofibre segments was observed (median length 144 µm), most of which were observed to fuse further along the parent fibre. Central nuclei were frequently observed at the point of branching/fusion. The branch commonly presented with a more immature profile (nestin + , neonatal myosin + , disorganised myofilaments) than the parent myofibre, together suggesting fusion of the branch, rather than splitting. Of the 210 regenerating muscle fibres evaluated, 99.5% were type II fibres, indicating preferential damage to type II fibres with our protocol. Furthermore, these fibres demonstrated 7 different stages of "fibre-type" profiles. CONCLUSIONS: By studying the regenerating tissue 30 days later with a range of microscopy techniques, we find that so-called myofibre branching or splitting is more likely to be fusion of myotubes and is therefore explained by incomplete regeneration after a necrosis-inducing event.
