SUMMARY: Streptococcus pyogenes, also known as group AStreptococcus(GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development.

Carbamazepine (CBZ), a pharmaceutical compound, has been proposed as an anthropogenic marker to assess water quality due to its persistence in conventional treatment plants and widespread presence in water bodies. This paper presents a comprehensive literature review on sources and occurrences of CBZ in water bodies, as well as toxicological effects and regulations of the drug. Given the documented side effects of CBZ on the human body when taken medicinally, its careful monitoring in water is recommended. CBZ residues in drinking water may provide a pathway to embryos and infants via intrauterine exposure or breast-feeding, which may cause congenital malformations and/or neurodevelopmental problems over long term exposure. An in-depth technical assessment of the conventional and advanced treatment technologies revealed the inadequacy of the standalone technologies. Compared to conventional activated sludge and membrane bioreactor processes, effective removal of CBZ can be achieved by nanofiltration and reverse osmosis membranes. However, recent studies have revealed that harsh chemical cleaning, as required to mitigate membrane fouling, can often reduce the long-term removal efficiency. Furthermore, despite the efficient performance of activated carbon adsorption and advanced oxidation processes, a few challenges such as cost of chemicals and regeneration of activated carbon need to be carefully considered. The limitations of the individual technologies point to the advantages of combined and hybrid systems, namely, membrane bioreactor coupled with nanofiltration, adsorption or advanced oxidation process.

A new variant of Streptococcus pyogenes serotype M1 (designated ‘M1_UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes ‘M1_global’ and M1_UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1_UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1_UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1_UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.