Identification of distinct impacts of CovS inactivation on the transcriptome of acapsular group A streptococci.
Sruti DebRoy, William C Shropshire, Luis Vega, Chau Tran, Nicola Horstmann, Piyali Mukherjee, Selvalakshmi Selvaraj-Anand, Truc T Tran, Jordan Bremer, Marc Gohel, Cesar A Arias, Anthony R Flores, Samuel A Shelburne
Author Information
Sruti DebRoy: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA. ORCID
William C Shropshire: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA. ORCID
Luis Vega: Division of Infectious Diseases and Department of Pediatrics, McGovern Medical School at UTHealth Houston and Children's Memorial Hermann Hospital , Houston, Texas, USA.
Chau Tran: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA.
Nicola Horstmann: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA.
Piyali Mukherjee: Division of Infectious Diseases and Department of Pediatrics, McGovern Medical School at UTHealth Houston and Children's Memorial Hermann Hospital , Houston, Texas, USA.
Selvalakshmi Selvaraj-Anand: School of Health Professions, The University of Texas MD Anderson Cancer Center , Houston, Texas, USA.
Truc T Tran: Center for Infectious Diseases, Houston Methodist Research Institute , Houston, Texas, USA.
Jordan Bremer: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA.
Marc Gohel: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA.
Cesar A Arias: Center for Infectious Diseases, Houston Methodist Research Institute , Houston, Texas, USA. ORCID
Anthony R Flores: Division of Infectious Diseases and Department of Pediatrics, McGovern Medical School at UTHealth Houston and Children's Memorial Hermann Hospital , Houston, Texas, USA. ORCID
Samuel A Shelburne: Department of Infectious Diseases Infection Control and Employee Health, University of Texas MD Anderson Cancer Center , Houston, Texas, USA. ORCID
Group A streptococcal (GAS) strains causing severe, invasive infections often have mutations in the control of virulence two-component regulatory system (CovRS) which represses capsule production, and high-level capsule production is considered critical to the GAS hypervirulent phenotype. Additionally, based on studies in GAS, hyperencapsulation is thought to limit transmission of CovRS-mutated strains by reducing GAS adherence to mucosal surfaces. It has recently been identified that about 30% of invasive GAS strains lacks capsule, but there are limited data regarding the impact of CovS inactivation in such acapsular strains. Using publicly available complete genomes ( = 2,455) of invasive GAS strains, we identified similar rates of CovRS inactivation and limited evidence for transmission of CovRS-mutated isolates for both encapsulated and acapsular types. Relative to encapsulated GAS, CovS transcriptomes of the prevalent acapsular types , , and revealed unique impacts such as increased transcript levels of genes in the /mga region along with decreased transcript levels of pilus operon-encoding genes and the streptokinase-encoding gene . CovS inactivation in and strains, but not , increased GAS survival in human blood. Moreover, CovS inactivation in acapsular GAS reduced adherence to host epithelial cells. These data suggest that the hypervirulence induced by CovS inactivation in acapsular GAS follows distinct pathways from the better studied encapsulated strains and that factors other than hyperencapsulation may account for the lack of transmission of CovRS-mutated strains. IMPORTANCE Devastating infections due to group A streptococci (GAS) tend to occur sporadically and are often caused by strains that contain mutations in the control of virulence regulatory system (CovRS). In well-studied GAS, the increased production of capsule induced by CovRS mutation is considered key to both hypervirulence and limited transmissibility by interfering with proteins that mediate attachment to eukaryotic cells. Herein, we show that the rates of covRS mutations and genetic clustering of CovRS-mutated isolates are independent of capsule status. Moreover, we found that CovS inactivation in multiple acapsular GAS types results in dramatically altered transcript levels of a diverse array of cell-surface protein-encoding genes and a unique transcriptome relative to encapsulated GAS. These data provide new insights into how a major human pathogen achieves hypervirulence and indicate that factors other than hyperencapsulation likely account for the sporadic nature of the severe GAS disease.
