Methicillin-resistant
Staphylococcus aureus
(MRSA) emerged as a major hypervirulent pathogen that causes severe health care-acquired infections. These pathogens can be multidrug-tolerant cells, which can facilitate the recurrence of chronic infections and the emergence of diverse antibiotic-resistant mutants.
Cellular self-digestion is an evolutionarily conserved process occurring in prokaryotic cells that enables survival under stressful conditions by recycling essential energy molecules. Self-digestion, which is triggered by extracellular stress conditions, such as nutrient depletion and overpopulation, induces degradation of intracellular components. This self-inflicted damage renders the bacterium less fit to produce building blocks and resume growth upon exposure to fresh nutrients. However, self-digestion may also provide temporary protection from antibiotics until the self-digestion-mediated damage is repaired. In fact, many persistence mechanisms identified to date may be directly or indirectly related to self-digestion, as these processes are also mediated by many degradative enzymes, including proteases and ribonucleases (RNases). In this review article, we will discuss the potential roles of self-digestion in bacterial persistence.
Methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to conventional antibiotics. These pathogens can form persister cells, which are transiently tolerant to bactericidal antibiotics, making them extremely dangerous. Previous studies have shown the effectiveness of proton motive force (PMF) inhibitors at killing bacterial cells; however, whether these agents can launch a new treatment strategy to eliminate persister cells mandates further investigation. Here, using known PMF inhibitors and two different MRSA isolates, we showed that antipersister potency of PMF inhibitors seemed to correlate with their ability to disrupt PMF and permeabilize cell membranes. By screening a small chemical library to verify this correlation, we identified a subset of chemicals (including nordihydroguaiaretic acid, gossypol, trifluoperazine, and amitriptyline) that strongly disrupted PMF in MRSA cells by dissipating either the transmembrane electric potential (ΔΨ) or the proton gradient (ΔpH). These drugs robustly permeabilized cell membranes and reduced persister levels below the limit of detection. Overall, our study further highlights the importance of cellular PMF as a target for designing new antipersister therapeutics.
Microalga is a primary source for third generation biofuels due to its high photosynthetic ability, which can be exploited to produce bioethanol, biodiesel, biohydrogen, as well as value-added coproducts such as proteins, carbohydrate, vitamin, omega fats, carotenoids etc. Using glycerol (a primary by-product of biodiesel industry) for mixotrophic algal cultivation can improve the economic and environmental sustainability of the biodiesel industry.Chlorella sorokiniana is cultured mixotrophically in modified TAP media using glycerol as the sole organic carbon source and atmospheric CO2 as the inorganic carbon source in a 1 L bubble column PBR with photoperiod of 18h :6h (Light:Dark). This study shows how theco-optimization of reactor scale parameters augments biomass yield at the cellular level by enhancing the synergy between autotrophic and heterotrophic pathways in the molecular level. A heterotrophic parameter (initial glycerol loading) and an autotrophic parameter (reactor illumination) are employed to engineer the mixotrophic algal cultivation process. The operating range of reactor illumination and initial glycerol loading are 3500-14000 Lux and 0.6-2.2 mL/L, respectively.
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