In This Issue pubs.acs.org/journal/aidcbc
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USING QUORUM SENSING INHIBITORS TO COMBAT STAPHYLOCOCCUS AUREUS Treatment of human bacterial infections has become increasingly complex due to the emergence of antibioticresistant pathogen strains. Particularly concerning is the rise of methicillin-resistant strains of the pathogen Staphylococcus aureus (MRSA). This requires the development of novel treatment strategies that circumvent contributing to the emergence of antibiotic resistance. In this issue, Kratochvil et al. (DOI: 10.1021/acsinfecdis. 6b00173) report their approach to target pathogenic S. aureus using quorum-sensing inhibitors. Quorum sensing is a bacterial signaling system that allows communication between cells and plays a crucial role in certain bacterial behaviors, such as virulence. In S. aureus, this process is governed by an autoinducing peptide (AIP) signal that induces expression of virulence factors relevant to infection upon binding to the transmembrane receptor, AgrC. Building on their previous work with a synthetic macrocyclic mimic of the AIP signal that inhibits quorum sensing, the authors used a fiber production technique called electrospinning to load the mimic into degradable polymer nanofibers. Biological evaluation revealed the release of the inhibitor from the polymer nanofibers, during which it retained its activity and inhibited quorum sensing in S. aureus without causing cell death. This approach of treating pathogenic bacteria by targeting their virulence instead of their growth could lead the way to new treatment strategies.
The innate immune receptor nucleotide-binding oligmerization domain-containing 2 (Nod2) is the most important protein implicated in the cause of the disease. Nod 2 binds to muramyl dipeptide (MDP) found on both Gram-positive and Gramnegative bacteria, and the interaction of MDP to mutant forms of Nod2 elicits the immune response associated with Crohn’s disease. In this issue, Lauro et al. (DOI: 10.1021/acsinfecdis. 6b00154) explore the interaction between the leucine-rich repeat (LRR) domain of Nod2, a motif involved in pathogen recognition, and MDP. The authors report the first expression and purification of the human Nod2 LRR domain in Escherichia coli. Subsequent studies examined the interaction between wild type LRR and mutants relevant to Crohn’s disease with MDP, its glycan, and its peptide component using surface plasmon resonance. The authors obtained further insights into the binding mode of action through molecular modeling. Understanding the interactions between Nod2 and MDP could prove useful to the development of Crohn’s disease therapeutics.
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TARGETING PATHOGENIC MICROBES THROUGH PHOTODYNAMIC INACTIVATION To address the rising threat of antibiotic resistance, various alternative routes are actively investigated to combat pathogenic microbes. One such technique is antimicrobial photodynamic inactivation, which involves the combination of visible light and a photosensitizer to create reactive oxygen species that induce cell death. Applying this method to Gram-negative bacteria generally requires cationic photosensitizers due to the negatively charged outer membrane. In the present issue, Huang et al. (DOI: 10.1021/acsinfecdis. 7b00004) explore whether potassium iodide can potentiate the antimicrobial effect of Photofrin, a clinically approved photosensitizer unable to bind to Gram-negative bacteria. The authors applied this system to fungi and both Gram-negative and Gram-positive bacteria, upon which they observed cell killing. Mechanistic studies revealed generation of molecular iodine to be the cause of the observed antimicrobial activity. This study illustrates the repurposing of the already approved anticancer agent Photofrin that, in combination with potassium iodide, can act as a broad-range antimicrobial agent.
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UNDERSTANDING THE BINDING INTERACTIONS OF A RECEPTOR INVOLVED IN CROHN’S DISEASE Crohn’s disease is an inflammatory bowel disorder that is postulated to occur due to an abnormal response to bacteria. © 2017 American Chemical Society
Received: March 28, 2017 Published: April 14, 2017 263
DOI: 10.1021/acsinfecdis.7b00043 ACS Infect. Dis. 2017, 3, 263−263
