Study Suggests Pore-forming Exotoxin May Increase Virality of Strep A

Streptolysin O (SLO)—a pore-forming exotoxin that can increase the virulence of Streptococcus pyogenes (Streptococcus group A; Strep A)—may increase the hypervirulence of Strep A covR/S mutant strains, according to recent article published in the journal ASM. Mutant strains contribute to severe Strep A cases around the globe. If dendritic cells (DC) respond effectively, it could increase a person’s immunity against the disease.

“We found that SLO alters interactions with host cell populations and increases Strep A viability at sterile sites of the host, such as the blood, and that its absence results in significantly less virulence…This work underscores the importance of SLO in Strep A virulence,” the study authors wrote.

SLO inhibits phagocytosis via pore formation. When it was absent from the covR/S mutant or wild-type Strep A strain, the presence of DCs were higher.

Strep A can cause invasive and noninvasive infections that lead to high cases of global morbidity and mortality. Streptococcal-related diseases may cause more than 500,000 deaths each year, according to reports. DC and neutrophils are one of the body’s first lines of defense against infection, but covR/S mutants can inhibit their maturation and prevent effective protection.

The investigative team hypothesized that covR/S mutants upregulate SLO and causes it to become hypervirulent. They conducted a series of evaluations to better understand the significance of SLO in covR/S gene regulation and the pathogenesis of Strep A.

One trial looked at naïve mice infected with either the wild-type Strep A variant M1T1 5448 or covR/S mutant M1T1 5448AP. The results of the study showed that these infections increased DC deaths in the mice, with the latter mutant killing more DCs.

A different evaluation in the study looked at the DC-harming mechanism of covR/S mutant M1T1 5448AP. The data showed that the M1T1 5448AP had a significantly greater level of slo gene expression. The investigation further suggested that the 5448AP Strep A variant could be more virulent because of a cumulative effective of several factors, including the upregulation of SLO RNA transcriptions and the streptococcal CXC chemokine protease, SpyCEP, according to the investigators.

“SLO is secreted by nearly all Strep A isolates,” the study authors wrote. “Our data show that SLO is an essential factor for covR/S mutant-mediated hypervirulence.”

There are currently no licensed Strep A vaccines on the market. Investigators suggest that experimental vaccines are in various stages of preclinical development, showing promise to reduce the spread and severity of Strep A.

“Understanding the complexities of the host-pathogen interaction is vital to the advancement of infection treatment and control and the development of effective vaccines,” the study authors wrote in the report.

Reference

Langshaw E, Reynolds S, Ozberk V, et al. Streptolysin O Deficiency in Streptococcus pyogenes M1T1 covR/S Mutant Strain Attenuates Virulence in In Vitro and In Vivo Infection Models. MicroNow. February 6, 2023. Accessed on February 9, 2023. doi.org/10.1128/mbio.03488-22