Hemolysins of <i>Staphylococcus aureus</i>—An Update on Their Biology, Role in Pathogenesis and as Targets for Anti-Virulence Therapy

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.

A Simple Sample Processing Protocol and Multiplex PCR for Direct Detection of MRSA from Uncultured Clinical Samples—A Pilot Study

Phenotypic tests have limited discrimatory power to identify closely related members of genus Staphylococcus and particularly for identification of S. aureus. 157 isolates of S. aureus obtained from different clinical specimens were included in our study. To present a demonstration of our method’s sensitivity and ability to correctly detect S. aureus from uncultured clinical specimen, 30 known S. aureus positive but leftover uncultured clinical specimens from clinical microbiology laboratory were processed by our protocol and analyzed. All the 30 clinical specimens were confirmed as S. aureus among which 26 specimen were identified as MRSA and the remaining 4 as MSSA. These 30 clinical specimens used in the study showed 100% correlation with coagulase test and Cefoxitin disc diffusion method. Though commercial molecular diagnostic kits are available for detecting MRSA from swabs, this is probably the first time that multiplex PCR is being demonstrated directly on a variety of uncultured clinical specimens.