Study of the IgG endoglycosidase EndoS in group A streptococcal phagocyte resistance and virulence
1 Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden
2 Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, Mail Code 0687, La Jolla, CA 92093, USA
3 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, Mail Code 0687, La Jolla, CA 92093, USA
4 School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
BMC Microbiology 2011, 11:120 doi:10.1186/1471-2180-11-120Published: 27 May 2011
The secreted enzyme EndoS, an endoglycosidase from Streptococcus pyogenes, hydrolyzes the N-linked glycan of the constant region of immunoglobulin G (IgG) heavy chain and renders the antibody unable to interact with Fc receptors and elicit effector functions. In this study we couple targeted allelic replacement mutagenesis and heterologous expression to elucidate the contribution of EndoS to group A Streptococcus (GAS) phagocyte resistance and pathogenicity in vitro and in vivo.
Knocking out the EndoS gene in GAS M1T1 background revealed no significant differences in bacterial survival in immune cell killing assays or in a systemic mouse model of infection. However, exogenous addition and heterologous expression of EndoS was found to increase GAS resistance to killing by neutrophils and monocytes in vitro. Additionally, heterologous expression of EndoS in M49 GAS increased mouse virulence in vivo.
We conclude that in a highly virulent M1T1 background, EndoS has no significant impact on GAS phagocyte resistance and pathogenicity. However, local accumulation or high levels of expression of EndoS in certain GAS strains may contribute to virulence.