'GGFGGQ' repeats in Hfq of Acinetobacter baumannii are essential for nutrient utilization and virulence.

The nosocomial pathogen Acinetobacter baumannii is known for causing lung and soft tissue infections in immunocompromised hosts. Its ability to adapt to various environments through post-transcriptional gene regulation is key to its success. Central to this regulation is the RNA chaperone Hfq, which facilitates interactions between mRNA targets and their small RNA (sRNA) partners through a Sm-core domain. Notably, the A. baumannii Hfq protein has a uniquely long C-terminal domain (CTD) with GGFGGQ amino acid repeats and an acidic amino acid-rich C-terminal tip (C-tip). Previous research has shown the importance of the intact CTD for Hfq's functionality. Given the significance of the C-tip in E. coli Hfq, we examined the pathophysiological roles of the redundant 'GGFGGQ' repeats along with the C-tip of A. baumannii Hfq. We constructed several variations of Hfq protein with fewer 'GGFGGQ' repeats while preserving the C-tip, and variants with altered C-tip amino acid composition. We then studied their RNA interaction abilities and assessed the pathophysiological fitness and virulence of genome-complemented A. baumannii mutants. Our findings reveal that the redundancy of the 'GGFGGQ' repeats is crucial for Hfq's role in pathophysiological fitness and negatively impacts A. baumannii's virulence in a murine lung infection model. In addition, C-tip mutants exhibited a negative effect on both fitness and virulence, however, to a lesser extent than the other variants. These results underscore the importance of 'GGFGGQ' redundancy and acidic residues in Hfq's ribo-regulation and autoregulation, suggesting their critical role in establishing regulatory networks.

Small Molecule IITR08367 Potentiates Antibacterial Efficacy of Fosfomycin against Acinetobacter baumannii by Efflux Pump Inhibition.

Fosfomycin is a broad-spectrum single-dose therapy approved for treating lower urinary tract infections. Acinetobacter baumannii, one of the five major UTI-causing pathogens, is intrinsically resistant to fosfomycin. Reduced uptake and active efflux are major reasons for this intrinsic resistance. AbaF, a major facilitator superfamily class of transporter in A. baumannii, is responsible for fosfomycin efflux and biofilm formation. This study describes the identification and validation of a novel small-molecule efflux pump inhibitor that potentiates fosfomycin efficacy against A. baumannii. An AbaF inhibitor screening was performed against Escherichia coli KAM32/pUC18_abaF, using the noninhibitory concentration of 24 putative efflux pump inhibitors. The inhibitory activity of IITR08367 [bis(4-methylbenzyl) disufide] against fosfomycin/H+ antiport was validated using ethidium bromide efflux, quinacrine-based proton-sensitive fluorescence, and membrane depolarization assays. IITR08367 inhibits fosfomycin/H+ antiport activity by perturbing the transmembrane proton gradient. IITR08367 is a nontoxic molecule that potentiates fosfomycin activity against clinical strains of A. baumannii and prevents biofilm formation by inhibiting efflux pump (AbaF). The IITR08367-fosfomycin combination reduced bacterial burden by > 3 log10 in kidney and bladder tissue in the murine UTI model. Overall, fosfomycin, in combination with IITR08367, holds the potential to treat urinary tract infections caused by A. baumannii.

Environmental performance and international trade in China: The role of renewable energy and eco-innovation.

Renewable energy and green innovation can enhance environmental performance by encouraging international trade, as anticipated by the current theoretical framework. This study investigates how renewable energy and eco-innovation affect international trade and environmental performance using quarterly data series from 1981 to 2018 for China. The study applies a quantile-based autoregressive distributed lag model. The results indicate that environmental innovation and renewable energy are consistent with environmental quality, while trade openness and urbanization contribute to environmental degradation by stimulating CO2 emissions. In addition, the quantile causality test showed a bidirectional causality between renewable energy and CO2 emissions, trade openness and CO2 emissions, and urbanization and CO2 emissions. Additionally, the findings lend theoretical support for the formulation of environmentally protective policies to better understand the role of renewable energy in stimulating international trade, which eventually enhances environmental performance. Integr Environ Assess Manag 2022;18:813-823. © 2021 SETAC.

Effects of COVID-19 in E-learning on higher education institution students: the group comparison between male and female.

In response to the emerging and ever solution to the COVID-19 outbreak. This study proposes a theoretical framework based on literature and model to determined E-learning portal success. The study compared males and females to E-learning portal usage. The study objective is to check the difference between male and female E-learning portals' accessibility among the students' perspective. The study included service quality, system quality, information quality, user satisfaction, system use, and E-learning portal success. The empirical data of 280 students participated from the different universities of Malaysia through google surveys analyzed using the Partial Least Squares Structural Equation Modelling. The study further divided the full model into two domains, which are female and male. In the male model, information quality and system quality have direct relationships with user satisfaction. Information quality also supported the relationship with system use. At the same time, there is a positive relationship between user satisfaction and E-learning portals. Likewise, in the female model, E-service quality and Information quality both are supported by system use and user satisfaction. Similarly, system quality has a positive relationship with user satisfaction, and user satisfaction has a positive relationship with E-learning portals. The study will be further helpful for the Malaysian universities policy-makers such as top management, ministry of higher education, Malaysian universities union in designing the policies and programs on E-learning Portal Success in the country. The findings of the study reveal that males and females have a different level of in terms of usage of towards E-learning portals in Malaysian Universities.