Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence fact...Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.展开更多
Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of m...Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.展开更多
文摘Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.
文摘Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.
