A brief review on Group A Streptococcus pathogenesis and vaccine development

Abstract

Streptococcus pyogenes , also known as Group A Streptococcus (GAS), is a Gram-positive human-exclusive pathogen, responsible for more than 500 000 deaths annually worldwide. Upon infection, GAS commonly triggers mild symptoms such as pharyngitis, pyoderma and fever. However, recurrent infections or prolonged exposure to GAS might lead to life-threatening conditions. Necrotizing fasciitis, streptococcal toxic shock syndrome and post-immune mediated diseases, such as poststreptococcal glomerulonephritis, acute rheumatic fever and rheumatic heart disease, contribute to very high mortality rates in non-industrialized countries. Though an initial reduction in GAS infections was observed in high-income countries, global outbreaks of GAS, causing rheumatic fever and acute poststreptococcal glomerulonephritis, have been reported over the last decade. At the same time, our understanding of GAS pathogenesis and transmission has vastly increased, with detailed insight into the various stages of infection, beginning with adhesion, colonization and evasion of the host immune system. Despite deeper knowledge of the impact of GAS on the human body, the development of a successful vaccine for prophylaxis of GAS remains outstanding. In this review, we discuss the challenges involved in identifying a universal GAS vaccine and describe several potential vaccine candidates that we believe warrant pursuit.

CovS inactivation reduces CovR promoter binding at diverse virulence factor encoding genes in group A Streptococcus

“…The CovRS TCS is central to the tight regulation of a broad collection of potent virulence factors, that allow GAS to cause a variety of infectious syndromes even in previously healthy persons [5,35,[58][59][60][61][62]. Herein, using ChIP-seq we show that CovR directly regulates at least nineteen key GAS virulence factor encoding genes, which account for nearly all virulence factor encoding genes in the CovRS regulon.…”

Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

“…Novel cell targets pending the urgent modification of the composition of current antibacterial vaccines or the development of an entirely new framework and formulations are needed. The list of vaccines that may be much more effective after improvement includes those against the following bacterial species: Bordetella pertussis, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae [3][4][5][6]. In addition to the vaccines already on this WHO list, there are important targets (viruses and bacteria) for new vaccines that are currently of little social, scientific, financial and manufacturing interest.…”

Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll‐like receptor 2

“…GAS is associated with a wide range of diseases from self‐limiting primary infections to life‐threatening invasive diseases, as well as postinfection immune sequelae 1 . GAS causes approximately 700 million cases of pharyngitis annually worldwide 2 . While usually self‐limiting, increasing incidence of these mild symptoms can lead to invasive conditions such necrotizing fasciitis and streptococcal toxic shock syndrome.…”

“…1 GAS causes approximately 700 million cases of pharyngitis annually worldwide. 2 While usually self-limiting, increasing incidence of these mild symptoms can lead to invasive conditions such necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, the greatest burden is attributed to postinfection complications that can cause lifelong injuries and premature deaths, such as acute rheumatic fever and rheumatic heart disease.…”