Evaluation of inhalation risk during quarantine work with quaternary ammonium compounds-based disinfectant.

Quarantine work is widely recognized as an indispensable endeavor in curbing the propagation of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, the heavy workload places workers at a heightened risk of chemical exposure and respiratory damage. Consequently, it is paramount to systematically perform health risk assessments and meticulously oversee the work by wearing personal protective equipment to minimize these risks. To assess the inhalation exposure, this study examined data on disinfectant exposure from quarantine professional users who utilized disinfectants containing quaternary ammonium compounds. Through a survey of 6,199 cases conducted by 300 quarantine professional users who actively engaged in quarantine work, we assembled a database of exposure factors derived from their utilization of spray-type disinfectants for quarantine purposes. Based on these data, we formulated an inhalation exposure algorithm, which considers the time-weighted average (TWA) air concentrations. The test results demonstrated that the industrial-grade respirator mask could prevent a minimum of 68.3 % of particles, reducing respiratory exposure. Consequently, the hazard quotient (HQ) due to disinfectant exposure also decreased. This research is essential in safeguarding the safety and health of professional users engaged in quarantine-related tasks. By implementing strict measures like health risk assessments and personal protective equipment, individuals with quarantine experience can safely carry out their quarantine work. The results of this study are expected to serve as a framework for improving policies and regulations concerning quarantine work and safeguarding the health of professional users.

The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses.

In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.

Autolysis of Pseudomonas aeruginosa Quorum-Sensing Mutant Is Suppressed by Staphylococcus aureus through Iron-Dependent Metabolism.

Microorganisms usually coexist as a multifaceted polymicrobial community in the natural habitats and at mucosal sites of the human body. Two opportunistic human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus commonly coexist in the bacterial infections for hospitalized and/or immunocompromised patients. Here, we observed that autolysis of the P. aeruginosa quorum-sensing (QS) mutant (lasRmvfR) was suppressed by the presence of the S. aureus cells in vitro. The QS mutant still displayed killing against S. aureus cells, suggesting the link between the S. aureus-killing activity and the autolysis suppression. Independent screens of the P. aeruginosa transposon mutants defective in the S. aureus-killing and the S. aureus transposon mutants devoid of the autolysis suppression revealed the genetic link between both phenotypes, suggesting that the iron-dependent metabolism involving S. aureus exoproteins might be central to both phenotypes. The autolysis was suppressed by iron treatment as well. These results suggest that the interaction between P. aeruginosa and S. aureus might be governed by mechanisms that necessitate the QS circuitry as well as the metabolism involving the extracellular iron resources during the polymicrobial infections in the human airway.

A TetR family regulator of an RND efflux system that directs artemisinin resistance in Vibrio cholerae.

Artemisinin (ARS) displayed bactericidal activity against Vibrio cholerae. To assess the mechanistic details of its antibacterial action, we have isolated V. cholerae mutants with enhanced ARS resistance and identified a gene (VCA0767) whose loss-of-function resulted in the ARS resistance phenotypes. This gene (atrR) encodes a TetR family transcriptional regulator, and its deletion mutant displayed the reduction in ARS-induced ROS formation and DNA damage. Transcriptomic analysis revealed that the genes encoding a resistance-nodulation-cell division (RND) efflux pump operon (vexRAB) and the outer membrane component (tolC) were highly upregulated in the artR mutant, suggesting that AtrR might act as a negative regulator of this operon and tolC. Gene deletion of vexR, vexB, or tolC abrogated the ARS resistance of the atrR mutant, and more importantly, the ectopic expression of VexAB-TolC was sufficient for the ARS resistance, indicating that the increased expression of the VexAB-TolC efflux system is necessary and sufficient for the ARS resistance of the atrR mutant. The cytoplasmic accumulation of ARS was compromised in the vexBtolC mutant, suggesting that the VexAB-TolC might be the primary efflux system exporting ARS to reduce its toxicity inside of the bacterial cells. The atrR mutant displayed resistance to erythromycin as well in a VexR-dependent manner. This result suggests that AtrR may act as a global regulator responsible for preventing intracellular accumulation of toxic chemicals by enhancing the RND efflux system.IMPORTANCEDrug efflux protein complexes or efflux pumps are considered as the major determinants of multiple antimicrobial resistance by exporting a wide range of structurally diverse antibiotics in bacterial pathogens. Despite the clinical significance of the increased expression of the efflux pumps, their substrate specificity and regulation mechanisms are poorly understood. Here, we demonstrated that VexAB-TolC, a resistance-nodulation-cell division (RND) efflux pump of V. cholerae, is responsible for the resistance to artemisinin (ARS), an antimalarial drug with bactericidal activity. Furthermore, we newly identified AtrR, a TetR family repressor, as a global regulator for VexRAB and the common outer membrane channel, TolC, where VexR functions as the pathway-specific regulator of the vexAB operon. Our findings will help improve our insight into a broad range of substrate specificity of the VexAB-TolC system and highlight the complex regulatory networks of the multiple RND efflux systems during V. cholerae pathogenesis.