Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1) and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α) production by human peripheral blood mononuclear cells (PBMC) and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.

3′,3′-cyclic GMP-AMP (cGAMP) is the third cyclic dinucleotide (CDN) to be discovered in bacteria. No activators of cGAMP signaling have yet been identified, and the signaling pathways for cGAMP have been inferred to display a narrow distribution based upon the characterized synthases, DncV and Hypr GGDEFs. Here, we report that the ubiquitous second messenger cyclic AMP (cAMP) is an activator of the Hypr GGDEF enzyme GacB from Myxococcus xanthus. Furthermore, we show that GacB is inhibited directly by cyclic di-GMP, which provides evidence for crossregulation between different CDN pathways. Finally, we reveal that the HD-GYP enzyme PmxA is a cGAMPspecific phosphodiesterase (GAP) that promotes resistance to osmotic stress in M. xanthus. A signature amino acid change in PmxA was found to reprogram substrate specificity and was applied to predict the presence of non-canonical HD-GYP phosphodiesterases in many bacterial species, including phyla previously not known to utilize cGAMP signaling.

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With advances in expressive speech synthesis and conversational understanding, an ever-increasing amount of digital content---including social and personal content---can be consumed through voice. Voice has long been known to convey personal characteristics and emotional states, both of which are prominent aspects of social media. Yet, no study has investigated voice design requirements for social media platforms. We interviewed 15 active social media users about their preferences on using synthesized voices to represent their profiles. Our findings show that participants want to have control over how a voice delivers their content, such as the personality and emotion with which the voice speaks, because these prosodic variations can impact users' online personas and interfere with impression management. We report motivations behind customizing or not customizing voice characteristics in different scenarios, and uncover key challenges around usability and the potential for stereotyping. We argue that synthesized speech for social media should be evaluated not only on listening experience and voice quality but also on its expressivity, degree of customizability, and ability to adapt to contexts (e.g., social media platforms, groups, individual posts). We discuss how our contribution confirms and extends knowledge of voice technology design and online self-presentation, and offer design considerations for voice personalization related to social interactions.