Variation in SeM genotype is associated with virulence of Streptococcus equi subspecies equi in mice.

Overview

• This study investigated how genetic differences in the M protein (seM) of Streptococcus equi subspecies equi influence the severity of infection in mice.
• Researchers found that distinct seM alleles correlate with different levels of virulence, from mild symptoms to death, suggesting that M protein genotype affects the bacteria’s harmfulness.

Background and Importance

• Strangles disease: A common infectious disease primarily affecting the upper respiratory tract of horses, caused by the bacterium Streptococcus equi subspecies equi (S. equi).
• M protein (seM): A key bacterial surface protein involved in immune evasion and pathogenicity. Genetic variations in seM may affect how the immune system recognizes the bacteria.
• Allelic diversity: To date, 271 different seM alleles have been identified, indicating a high degree of genetic variability among S. equi strains.
• Understanding how these genetic differences impact virulence is important for disease control and vaccine development.

Objective of the Study

• To evaluate the virulence (disease-causing ability) of different S. equi isolates representing various seM alleles in an experimental mouse model.
• To determine whether specific seM genotypes correspond to more severe clinical outcomes following infection.

Methods

• Animals: 36 Swiss mice divided into 12 groups (G1-G12), each group infected with a different S. equi isolate.
• Isolates: Included isolates representing seM alleles seM-117, seM-61, seM-123, seM-115, seM-271, seM-124, seM-158, seM-39, a no allele strain, seM-28, and two control groups with no infection.
• Infection protocol: Mice were infected intranasally with 2 × 10^7 CFU/mL of each isolate.
• Monitoring: Clinical signs (such as lethargy, nasal discharge, breathing difficulty, neurological symptoms), body weight, and nasal bacterial shedding were recorded daily for 10 days.

Findings

• Variable clinical outcomes: Depending on seM allele, mice showed a spectrum of disease severity:
• Highly virulent isolates (seM-158, seM-39, seM-271): Frequently caused death or required euthanasia; consistent bacterial shedding and enlarged lymph nodes were observed.
• Moderate virulence (seM-115, seM-124, no allele, seM-28): Mice displayed moderately severe clinical signs without consistently fatal outcomes.
• Mild or no symptoms (seM-117, seM-61, seM-123): Mice either had mild disease or remained asymptomatic.
• Control mice: No infection, no clinical signs as expected.

Conclusions and Implications

• S. equi isolates vary substantially in their ability to cause disease, and this variation is associated with differences in the seM gene.
• Some seM genotypes are linked with severe disease manifestations in mice, indicating that the M protein plays a role in virulence.
• These findings suggest potential for predicting disease severity or tailoring treatments and preventative strategies based on M protein genotype.
• Further research is needed to determine if similar virulence patterns related to seM genotype occur in horses, the natural host, and to establish whether the association is direct or if other factors contribute.
• Understanding this could improve vaccine design and epidemiological tracking of strangles outbreaks.