Commensal-derived short-chain fatty acids disrupt lipid membrane homeostasis in Staphylococcus aureus.

The role of commensal anaerobic bacteria in chronic respiratory infections is unclear, yet they can exist in abundances comparable to canonical pathogens in vivo. Their contributions to the metabolic landscape of the host environment may influence pathogen behavior by competing for nutrients and creating inhospitable conditions via toxic metabolites. Here, we reveal a mechanism by which the anaerobe-derived short chain fatty acids (SCFAs) propionate and butyrate negatively affect Staphylococcus aureus physiology by disrupting branched chain fatty acid (BCFA) metabolism. In turn, BCFA impairment results in impaired growth, diminished expression of the agr quorum sensing system, as well as increased sensitivity to membrane-targeting antimicrobials. Altered BCFA metabolism also reduces S. aureus fitness in competition with Pseudomonas aeruginosa, suggesting that airway microbiome composition and the metabolites they produce and exchange directly impact pathogen succession over time. The pleiotropic effects of these SCFAs on S. aureus fitness and their ubiquity as metabolites in animals also suggests that they may be effective as sensitizers to traditional antimicrobial agents when used in combination.

Evaluation of Expanded 2-Aminobenzothiazole Library for Inhibition of Pseudomonas aeruginosa Virulence Phenotypes.

Bacterial resistance to antibiotics is a rapidly increasing threat to human health. New strategies to combat resistant organisms are desperately needed. One potential avenue is targeting two-component systems, which are the main bacterial signal transduction pathways used to regulate development, metabolism, virulence, and antibiotic resistance. These systems consist of a homodimeric membrane-bound sensor histidine kinase, and a cognate effector, the response regulator. The high sequence conservation in the catalytic and adenosine triphosphate-binding (CA) domain of histidine kinases and their essential role in bacterial signal transduction could enable broad-spectrum antibacterial activity. Through this signal transduction, histidine kinases regulate multiple virulence mechanisms including toxin production, immune evasion, and antibiotic resistance. Targeting virulence, as opposed to development of bactericidal compounds, could reduce evolutionary pressure for acquired resistance. Additionally, compounds targeting the CA domain have the potential to impair multiple two-component systems that regulate virulence in one or more pathogens. We conducted structure-activity relationship studies of 2-aminobenzothiazole-based inhibitors designed to target the CA domain of histidine kinases. We found these compounds have anti-virulence activities in Pseudomonas aeruginosa, reducing motility phenotypes and toxin production associated with the pathogenic functions of this bacterium.

Effect of Face Masks on Physiological and Perceptual Responses during 30 Minutes of Self-Paced Exercise in Older Community Dwelling Adults.

This study examined the effects of different types of masks (no mask, surgical mask (SM), and N95-mask) on physiological and perceptual responses during 30-min of self-paced cycle ergometer exercise. This study was a prospective randomly assigned experimental design. Outcomes included workload (Watts), oxygen saturation (SpO2), end-tidal carbon dioxide (PetCO2), heart rate (HR), respiratory rate (RR), rating of perceived exertion (RPE), and rating of perceived dyspnea (RPD). Volunteers (54-83 years (n = 19)) completed two familiarization sessions and three testing sessions on an air braked cycle ergometer. No significant difference was found for condition x time for any of the dependent variables. RPE, RPD, and PetCO2 were significantly higher with an N95-mask vs. no mask (NM) ((p = 0.012), (p = 0.002), (p < 0.001)). HR was significantly higher with the SM compared to the NM condition (p = 0.027) (NM 107.18 ± 9.96) (SM 112.34 ± 10.28), but no significant difference was found when comparing the SM to the N95 condition or when comparing the N95condition to the NM condition. Watts increased across time in each condition (p = 0.003). Initially RR increased during the first 3 min of exercise (p < 0.001) with an overall gradual increase noted across time regardless of mask condition (p < 0.001). SpO2 significantly decreased across time but remained within normal limits (>95%). No significant difference was found in Watts, RR, or SpO2 regardless of mask condition. Overall, the N95mask was associated with increased RPE, RPD, and PetCO2 levels. This suggests trapping of CO2 inside the mask leading to increased RPE and RPD.