A zero-sum game or an interactive frame?Iron competition between bacteriaand humans ininfectionwar

Iron is an essential trace element for both humans and bacteria.It plays a vital role in life,such as in redox reactions and electron transport.Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life.Competition for iron is a war between humans and bacteria.To grow,reproduce,colonize,and successfully cause infection,pathogens have evolved various mechanisms for iron uptake from humans,principally Fe^(3+)-siderophore and Fe^(2+)-heme transport systems.Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization.Meanwhile,researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron,to help eliminate pathogens.In this review,we summarize bacterial and human iron metabolism,competition for iron between humans and bacteria,siderophore sensors,antibiotics coupled with siderophores,and related phenomena.We also discuss how competition for iron can be used for diagnosis and treatment of infection inthefuture.

Prediction and analysis of human-herpes simplex virus type 1 protein-protein interactions by integrating multiple methods

Background:Herpes simplex virus type 1(HSV-1)is a ubiquitous infectious pathogen that widely affects human health.To decipher the complicated human-HSV-1 interactions,a comprehensive protein-protein interaction(PPI)network between human and HSV-1 is highly demanded.Methods:To complement the experimental identification of human-HSV-1 PPIs,an integrative strategy to predict proteome-wide PPIs between human and HSV-1 was developed.For each human-HSV-1 protein pair,four popular PPI inference methods,including interolog mapping,the domain-domain interaction-based method,the domain-motif interaction-based method,and the machine learning-based method,were optimally implemented to generate four interaction probability scores,which were further integrated into a final probability score.Results:As a result,a comprehensive high-confidence PPI network between human and HSV-1 was established,covering 10,432 interactions between 4,546 human proteins and 72 HSV-1 proteins.Functional and network analyses of the HSV-1 targeting proteins in the context of human interactome can recapitulate the known knowledge regarding the HSV-1 replication cycle,supporting the overall reliability of the predicted PPI network.Considering that HSV-1 infections are implicated in encephalitis and neurodegenerative diseases,we focused on exploring the biological significance of the brain-specific human-HSV-1 PPIs.In particular,the predicted interactions between HSV-1 proteins and Alzheimer's-disease-related proteins were intensively investigated.Conclusion:The current work can provide testable hypotheses to assist in the mechanistic understanding of the human-HSV-1 relationship and the anti-HSV-1 pharmaceutical target discovery.To make the predicted PPI network and the datasets freely accessible to the scientific community,a user-friendly database browser was released at http://www.zzdlab.com/HintHSV/index.php.