Abstract
Background Streptococcus suis is an important infectious agent for pigs and occasionally for humans. The host innate immune system plays a key role in preventing and eliminating S. suis infections. One important constituent of the innate immune system is the protein lysozyme, which is present in a variety of body fluids and immune cells. Lysozyme acts as a peptidoglycan degrading enzyme causing bacterial lysis. Several pathogens have developed mechanisms to evade lysozyme-mediated killing. In the present study we compared the lysozyme sensitivity of various S. suis isolates and investigated the molecular basis of lysozyme resistance for this pathogen.ResultsThe lysozyme minimal inhibitory concentrations of a wide panel of S. suis isolates varied between 0.3 to 10 mg/ml. By inactivating the oatA gene in a serotype 2 and a serotype 9 strain, we showed that OatA-mediated peptidoglycan modification partly contributes to lysozyme resistance. Furthermore, inactivation of the murMN operon provided evidence that additional peptidoglycan crosslinking is not involved in lysozyme resistance in S. suis. Besides a targeted approach, we also used an unbiased approach for identifying factors involved in lysozyme resistance. Based on whole genome comparisons of a lysozyme sensitive strain and selected lysozyme resistant derivatives, we detected several single nucleotide polymorphisms (SNPs) that were correlated with the lysozyme resistance trait. Two SNPs caused defects in protein expression of an autolysin and a capsule sugar transferase. Analysis of specific isogenic mutants, confirmed the involvement of autolysin activity and capsule structures in lysozyme resistance of S. suis.ConclusionsThis study shows that lysozyme resistance levels are highly variable among S. suis isolates and serotypes. Furthermore, the results show that lysozyme resistance in S. suis can involve different mechanisms including OatA-mediated peptidolycan modification, autolysin activity and capsule production.
Highlights
Streptococcus suis is an important pig pathogen causing severe infections including meningitis, septicemia, endocarditis, pneumonia and arthritis
The host innate immune system is an important factor in the prevention and elimination of S. suis infections, the involvement of pattern recognition receptors (PRRs) in sensing S. suis has recently been described [4,5]
Heterogeneous lysozyme resistance levels in S. suis To investigate lysozyme resistance levels in the S. suis species, the lysozyme minimal inhibitory concentration (MIC) was determined for a broad panel of S. suis isolates belonging to serotypes 1, 2, 7 or 9
Summary
Streptococcus suis is an important pig pathogen causing severe infections including meningitis, septicemia, endocarditis, pneumonia and arthritis. S. suis is a zoonotic agent displaying comparable disease manifestations in humans as are seen in pigs [1,2,3]. Little is known about the role of effector molecules of the innate immune system in counteracting S. suis infections. With anti-bacterial activity, is the protein lysozyme. Streptococcus suis is an important infectious agent for pigs and occasionally for humans. The host innate immune system plays a key role in preventing and eliminating S. suis infections. One important constituent of the innate immune system is the protein lysozyme, which is present in a variety of body fluids and immune cells. In the present study we compared the lysozyme sensitivity of various S. suis isolates and investigated the molecular basis of lysozyme resistance for this pathogen
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