Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs; SEA to SEE, SEG to SEI, SER to SET) with demonstrated emetic activity, and staphylococcal-like (SEl) proteins, which are not emetic in a primate model (SElL and SElQ) or have yet to be tested (SElJ, SElK, SElM to SElP, SElU, SElU2 and SElV). SEs and SEls have been traditionally subdivided into classical (SEA to SEE) and new (SEG to SElU2) types. All possess superantigenic activity and are encoded by accessory genetic elements, including plasmids, prophages, pathogenicity islands, vSa genomic islands, or by genes located next to the staphylococcal cassette chromosome (SCC) implicated in methicillin resistance. SEs are a major cause of food poisoning, which typically occurs after ingestion of different foods, particularly processed meat and dairy products, contaminated with S. aureus by improper handling and subsequent storage at elevated temperatures. Symptoms are of rapid onset and include nausea and violent vomiting, with or without diarrhea. The illness is usually self-limiting and only occasionally it is severe enough to warrant hospitalization. SEA is the most common cause of staphylococcal food poisoning worldwide, but the involvement of other classical SEs has been also demonstrated. Of the new SE/SEls, only SEH have clearly been associated with food poisoning. However, genes encoding novel SEs as well as SEls with untested emetic activity are widely represented in S. aureus, and their role in pathogenesis may be underestimated.

https://www.mdpi.com/2072-6651/2/7/1751/pdf

Food poisoning and Staphylococcus aureus enterotoxins.

Summary: The bacterial superantigens are protein toxins that bind to major histocompatibility complex class II and T-cell receptor to stimulate large numbers of T cells. The majority are produced by the Gram-positive organisms Staphylococcus aureus and Streptococcus pyogenes and are the causative agents in toxic shock syndrome, an acute disease caused by the sudden and massive release of T-cell cytokines into the blood stream. The structure and function of the superantigens has revealed a common architecture that is also shared by another group of staphylococcal virulence factors called the superantigen-like proteins (SSL). Together, this family of structurally related molecules highlights how a common pathogenic organism has employed a simple but adaptable protein to generate an armamentarium of potent defense molecules designed to target of the innate and adaptive immune response.

The bacterial superantigen and superantigen-like proteins.

Bacteria such as Staphylococcus aureus are successful as commensal organisms or pathogens in part because they adapt rapidly to selective pressures imparted by the human host. Mobile genetic elements (MGEs) play a central role in this adaptation process and are a means to transfer genetic information (DNA) among and within bacterial species. Importantly, MGEs encode putative virulence factors and molecules that confer resistance to antibiotics, including the gene that confers resistance to beta-lactam antibiotics in methicillin-resistant S. aureus (MRSA). Inasmuch as MRSA infections are a significant problem worldwide and continue to emerge in epidemic waves, there has been significant effort to improve diagnostic assays and to develop new antimicrobial agents for treatment of disease. Our understanding of S. aureus MGEs and the molecules they encode has played an important role toward these ends and has provided detailed insight into the evolution of antimicrobial resistance mechanisms and virulence.

/pdf/mobile-genetic-elements-of-staphylococcus-aureus-qg2sxcvsa7.pdf

Mobile genetic elements of Staphylococcus aureus

The phage-related chromosomal islands (PRCIs) were first identified in Staphylococcus aureus as highly mobile, superantigen-encoding genetic elements known as the S. aureus pathogenicity islands (SaPIs). These elements are characterized by a specific set of phage-related functions that enable them to use the phage reproduction cycle for their own transduction and inhibit phage reproduction in the process. SaPIs produce many phage-like infectious particles; their streptococcal counterparts have a role in gene regulation but may not be infectious. These elements therefore represent phage satellites or parasites, not defective phages. In this Review, we discuss the shared genetic content of PRCIs, their life cycle and their ability to be transferred across large phylogenetic distances.

The phage-related chromosomal islands of Gram-positive bacteria.

Because bacteriophages generally parasitize only closely related bacteria, it is assumed that phage-mediated genetic exchange occurs primarily within species. Here we report that staphylococcal pathogenenicity islands, containing superantigen genes, and other mobile elements transferred to Listeria monocytogenes at the same high frequencies as they transfer within Staphylococcus aureus. Several staphylococcal phages transduced L. monocytogenes but could not form plaques. In an experiment modeling phage therapy for bovine mastitis, we observed pathogenicity island transfer between S. aureus and L. monocytogenes in raw milk. Thus, phages may participate in a far more expansive network of genetic information exchange among bacteria of different species than originally thought, with important implications for the evolution of human pathogens.

https://science.sciencemag.org/content/sci/323/5910/139.full.pdf

Phage-Mediated Intergeneric Transfer of Toxin Genes

Evidence of dysregulation of dendritic cells in primary HIV infection.

The SaPIs are 15- to 17-kb mobile pathogenicity islands in staphylococci. They usually carry two or more superantigens and are responsible for most superantigen-related human diseases, especially staphylococcal toxic shock syndrome. SaPIs are extremely common in Staphylococcus aureus, with all but one of the sequenced genomes containing one or more. The SaPIs have a highly conserved overall genome organization, parallel to that of typical temperate phages. Each occupies a specific chromosomal site from which it is induced to excise and replicate by one or more specific staphylococcal phages. Following replication, the SaPI DNA is efficiently encapsidated into infectious small-headed phage-like particles, resulting in extremely high transfer frequencies.

The SaPIs: mobile pathogenicity islands of Staphylococcus.

SaPIs are a family of homologous phage-related pathogenicity islands in staphylococci that carry superantigen and other virulence genes, and are responsible for a wide variety of superantigen-related diseases. SaPIs are induced to excise and replicate by particular staphylococcal phages and are encapsidated in infectious, small-headed, phage-like particles, which are transmitted at very high frequency among staphylococcal strains and species. SaPI2 is a prototypical member of this family that was identified in a typical menstrual toxic shock syndrome (TSS) strain of Staphylococcus aureus, the so-called Harrisburg strain, and found to be mobilizable by typing phage 80. Most menstrual TSS strains belong to a highly uniform agr group III clone of electrophoretic type (ET) 41, and this study was undertaken to determine whether such strains typically carry SaPI2, and whether it has spread beyond the ET41 clone. We report here the complete sequence of SaPI2, describe its relation to other known SaPIs, and show that it, or a very similar element, is carried by most ET41 strains but that it has disseminated to other strains that have also been implicated in TSS. We show additionally, that SaPIs are widespread among the staphylococci and that most TSS strains carry two or more, including SaPI2.

/pdf/sequence-analysis-reveals-genetic-exchanges-and-1woacdau84.pdf

Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock.

The nucleus incertus (NI), a conserved hindbrain structure implicated in the stress response, arousal, and memory, is a major site for production of the neuropeptide relaxin-3. On the basis of goosecoid homeobox 2 (gsc2) expression, we identified a neuronal cluster that lies adjacent to relaxin 3a (rln3a) neurons in the zebrafish analogue of the NI. To delineate the characteristics of the gsc2 and rln3a NI neurons, we used CRISPR/Cas9 targeted integration to drive gene expression specifically in each neuronal group, and found that they differ in their efferent and afferent connectivity, spontaneous activity, and functional properties. gsc2 and rln3a NI neurons have widely divergent projection patterns and innervate distinct subregions of the midbrain interpeduncular nucleus (IPN). Whereas gsc2 neurons are activated by electric shock, rln3a neurons exhibit spontaneous fluctuations in calcium signaling and regulate locomotor activity. Our findings define heterogeneous neurons in the NI and provide new tools to probe its diverse functions.

/pdf/genetically-defined-nucleus-incertus-neurons-differ-in-2teyexx3.pdf

Abhignya Subedi

Papers

Evidence of dysregulation of dendritic cells in primary HIV infection.

The SaPIs: mobile pathogenicity islands of Staphylococcus.

Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock.

Genetically defined nucleus incertus neurons differ in connectivity and function