Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens.

The development of sustainable alternatives to conventional antimicrobials is needed to address bacterial virulence while avoiding selecting resistant strains in a variety of fields, including human, animal, and plant health. Quorum sensing (QS), a bacterial communication system involved in noxious bacterial phenotypes such as virulence, motility, and biofilm formation, is of utmost interest. In this study, we harnessed the potential of the lactonase SsoPox to disrupt QS of human, fish, and plant pathogens. Lactonase treatment significantly alters phenotypes including biofilm formation, motility, and infection capacity. In plant pathogens, SsoPox decreased the production of plant cell wall degrading enzymes in Pectobacterium carotovorum and reduced the maceration of onions infected by Burkholderia glumae. In human pathogens, lactonase treatment significantly reduced biofilm formation in Acinetobacter baumannii, Burkholderia cepacia, and Pseudomonas aeruginosa, with the cytotoxicity of the latter being reduced by SsoPox treatment. In fish pathogens, lactonase treatment inhibited biofilm formation and bioluminescence in Vibrio harveyi and affected QS regulation in Aeromonas salmonicida. QS inhibition can thus be used to largely impact the virulence of bacterial pathogens and would constitute a global and sustainable approach for public, crop, and livestock health in line with the expectations of the One Health initiative.

AHL-Based Quorum Sensing Regulates the Biosynthesis of a Variety of Bioactive Molecules in Bacteria.

Bacteria are social microorganisms that use communication systems known as quorum sensing (QS) to regulate diverse cellular behaviors including the production of various secreted molecules. Bacterial secondary metabolites are widely studied for their bioactivities including antibiotic, antifungal, antiparasitic, and cytotoxic compounds. Besides playing a crucial role in natural bacterial niches and intermicrobial competition by targeting neighboring organisms and conferring survival advantages to the producer, these bioactive molecules may be of prime interest to develop new antimicrobials or anticancer therapies. This review focuses on bioactive compounds produced under acyl homoserine lactone-based QS regulation by Gram-negative bacteria that are pathogenic to humans and animals, including the Burkholderia, Serratia, Pseudomonas, Chromobacterium, and Pseudoalteromonas genera. The synthesis, regulation, chemical nature, biocidal effects, and potential applications of these identified toxic molecules are presented and discussed in light of their role in microbial interactions.

Lactonase-mediated inhibition of quorum sensing largely alters phenotypes, proteome, and antimicrobial activities in Burkholderia thailandensis E264.

Introduction: Burkholderia thailandensis is a study model for Burkholderia pseudomallei, a highly virulent pathogen, known to be the causative agent of melioidosis and a potential bioterrorism agent. These two bacteria use an (acyl-homoserine lactone) AHL-mediated quorum sensing (QS) system to regulate different behaviors including biofilm formation, secondary metabolite productions, and motility. Methods: Using an enzyme-based quorum quenching (QQ) strategy, with the lactonase SsoPox having the best activity on B. thailandensis AHLs, we evaluated the importance of QS in B. thailandensis by combining proteomic and phenotypic analyses. Results: We demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases B. thailandensis bactericidal activity against two bacteria (Chromobacterium violaceum and Staphylococcus aureus), while a spectacular increase in antifungal activity was observed against fungi and yeast (Aspergillus niger, Fusarium graminearum and Saccharomyces cerevisiae). Discussion: This study provides evidence that QS is of prime interest when it comes to understanding the virulence of Burkholderia species and developing alternative treatments.

Potential effects of multimodal psychosomatic inpatient treatment for patients with functional vertigo and dizziness symptoms - A pilot trial.

OBJECTIVES: Functional vertigo and dizziness (VD) are frequent and severely distressing complaints that are often described as hard to treat. Our aim was to provide preliminary data on potential effects of multimodal psychosomatic inpatient therapy for patients with functional VD symptoms in reducing vertigo-related handicap and related psychopathology, and to evaluate the role of symptom burden and body-related locus of control in predicting vertigo-related handicap at follow-up. DESIGN: We conducted an uncontrolled clinical pilot trial. METHODS: We included data of n = 72 inpatients with functional VD as a primary symptom and various psychopathological and/or physical comorbidities admitted for multimodal psychosomatic inpatient treatment. Patients completed self-report questionnaires assessing vertigo-related handicap (VHQ), somatization (PHQ-15), depression (BDI-II), anxiety (BAI), health-related quality of life (HRQOL; SF-36), and body-related locus of control (KLC) at admission (T0), discharge (T1), and 6 months after discharge (T2). RESULTS: We observed medium effects for the change of vertigo-related handicap (T0-T1: g = -0.60, T0-T2: g = -0.67) and small effects for the change of somatization (T0-T1: g = -0.29, T0-T2: g = -0.24), mental HRQOL (T0-T1: g = 0.43, T0-T2: g = 0.49), and depression (T0-T1: g = -0.41, T0-T2: g = -0.28) from admission to discharge and admission to follow-up. Body-related locus of control did not predict vertigo-related handicap at follow-up. CONCLUSIONS: Findings provide preliminary evidence for the beneficial role of psychosomatic inpatient treatment for patients with functional VD symptoms. Potentially relevant predictors of outcome at follow-up are discussed. PRACTITIONER POINTS: The change of vertigo-related handicap and related variables through multimodal psychosomatic inpatient treatment was evaluated in a clinical pilot trial in patients with functional vertigo and dizziness. We observed medium effects for the change of vertigo-related handicap and small effects for the change of somatization, mental health-related quality of life, and depression. Internal body-related locus of control at admission did not predict vertigo-related handicap at follow-up.

Adapting and implementing an evidence-based sun-safety education program in rural Idaho, 2012.

BACKGROUND: Melanoma incidence and mortality rates in Idaho are higher than national averages. The importance of increased awareness of skin cancer has been cited by state and local organizations. St. Luke's Mountain States Tumor Institute (MSTI) prioritized educational outreach efforts to focus on the implementation of a skin cancer prevention program in rural Idaho. COMMUNITY CONTEXT: As a community cancer center, MSTI expanded cancer education services to include dedicated support to rural communities. Through this expansion, an MSTI educator sought to partner with a community organization to provide sun-safety education. MSTI selected, adapted, and implemented an evidence-based program, Pool Cool. METHODS: The education program was implemented in 5 phases. In Phase I, we identified and recruited a community partner; in Phase 2, after thorough research, we selected a program, Pool Cool; in Phase 3, we planned the details of the program, including identification of desired short- and long-term outcomes and adaptation of existing program materials; in Phase 4, we implemented the program in summer 2012; in Phase 5, we assessed program sustainability and expansion. OUTCOME: MSTI developed a sustainable partnership with Payette Municipal Pool, and in summer 2012, we implemented Pool Cool. Sun-safety education was provided to more than 700 young people aged 2 to 17 years, and educational signage and sunscreen benefitted hundreds of additional pool patrons. INTERPRETATION: Community cancer centers are increasingly being asked to assess community needs and implement evidence-based prevention and screening programs. Clinical staff may become facilitators of evidence-based public health programs. Challenges of implementing evidence-based programs in the context of a community cancer centers are staffing, leveraging of resources, and ongoing training and support.