Hypothiocyanite and host-microbe interactions.

The pseudohypohalous acid hypothiocyanite/hypothiocyanous acid (OSCN- /HOSCN) has been known to play an antimicrobial role in mammalian immunity for decades. It is a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN- ) and hydrogen peroxide (H2 O2 ) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste. However, despite the well-recognized antibacterial role HOSCN plays in host-pathogen interactions, little is known about how bacteria sense and respond to this oxidant. In this work, we will summarize what is known and unknown about HOSCN in innate immunity and recent advances in understanding the responses that both pathogenic and non-pathogenic bacteria mount against this antimicrobial agent, highlighting studies done with three model organisms, Escherichia coli, Streptococcus spp., and Pseudomonas aeruginosa.

Escherichia coli RclA is a highly active hypothiocyanite reductase.

Hypothiocyanite and hypothiocyanous acid (OSCN-/HOSCN) are pseudohypohalous acids released by the innate immune system which are capable of rapidly oxidizing sulfur-containing amino acids, causing significant protein aggregation and damage to invading bacteria. HOSCN is abundant in saliva and airway secretions and has long been considered a highly specific antimicrobial that is nearly harmless to mammalian cells. However, certain bacteria, commensal and pathogenic, are able to escape damage by HOSCN and other harmful antimicrobials during inflammation, which allows them to continue to grow and, in some cases, cause severe disease. The exact genes or mechanisms by which bacteria respond to HOSCN have not yet been elucidated. We have found, in Escherichia coli, that the flavoprotein RclA, previously implicated in reactive chlorine resistance, reduces HOSCN to thiocyanate with near-perfect catalytic efficiency and strongly protects E. coli against HOSCN toxicity. This is notable in E. coli because this species thrives in the chronically inflamed environment found in patients with inflammatory bowel disease and is able to compete with and outgrow other important commensal organisms, suggesting that HOSCN may be a relevant antimicrobial in the gut, which has not previously been explored. RclA is conserved in a variety of epithelium-colonizing bacteria, implicating its HOSCN reductase activity in a variety of host-microbe interactions. We show that an rclA mutant of the probiotic Limosilactobacillus reuteri is sensitive to HOSCN and that RclA homologs from Staphylococcus aureus, Streptococcus pneumoniae, and Bacteroides thetaiotaomicron all have potent protective activity against HOSCN when expressed in E. coli.

Fragments of ATP synthase mediate plant perception of insect attack.

Plants can perceive a wide range of biotic attackers and respond with targeted induced defenses. Specificity in plant non-self-recognition occurs either directly by perception of pest-derived elicitors or indirectly through resistance protein recognition of host targets that are inappropriately proteolyzed. Indirect plant perception can occur during interactions with pathogens, yet evidence for analogous events mediating the detection of insect herbivores remains elusive. Here we report indirect perception of herbivory in cowpea (Vigna unguiculata) plants attacked by fall armyworm (Spodoptera frugiperda) larvae. We isolated and identified a disulfide-bridged peptide (+ICDINGVCVDA-), termed inceptin, from S. frugiperda larval oral secretions that promotes cowpea ethylene production at 1 fmol leaf(-1) and triggers increases in the defense-related phytohormones salicylic acid and jasmonic acid. Inceptins are proteolytic fragments of chloroplastic ATP synthase gamma-subunit regulatory regions that mediate plant perception of herbivory through the induction of volatile, phenylpropanoid, and protease inhibitor defenses. Only S. frugiperda larvae that previously ingested chloroplastic ATP synthase gamma-subunit proteins and produced inceptins significantly induced cowpea defenses after herbivory. Digestive fragments of an ancient and essential plant enzyme, inceptin functions as a potent indirect signal initiating specific plant responses to insect attack.