Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

Bas G J Surewaard,Jos A G Van Strijp,András N Spaan,Reindert Nijland,Carla J C De Haas,John A W Kruijtzer,Michael S Gilmore

doi:10.1371/journal.ppat.1002606

Bas G J Surewaard, Jos A G Van Strijp + Show 5 more

Open Access

https://doi.org/10.1371/journal.ppat.1002606

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Abstract

Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered.

Highlights

Staphylococcus aureus frequently colonizes human anterior nares and can cause many infectious diseases, ranging from mild superficial skin and wound infections to life-threatening disseminated infections [1]
CA-methicillin-resistant S. aureus (MRSA) strains are associated with high productions of phenol soluble modulins (PSM), which is thought to account for the enhanced virulence, easier spreading and severity of infection of CA-MRSA strains compared to hospital-acquired MRSA strains (HA-MRSA) [6,7]
Enhanced virulence of CAMRSA is thought to be associated with the production of several toxins, such as Phenol Soluble Modulins (PSM)

Summary

Introduction

Staphylococcus aureus frequently colonizes human anterior nares and can cause many infectious diseases, ranging from mild superficial skin and wound infections to life-threatening disseminated infections [1]. The number of infections by this bacterium is increasing, especially infections caused by methicillin-resistant S. aureus (MRSA) strains. Infections are still limited to a small percentage of colonized individuals. This suggests that the human innate immune system together with physical and humoral barriers can very effectively control invasive infections, even those caused by the invasive community-associated (CA) MRSA. We hypothesize that virulence factors produced by S. aureus are likely generally counteracted by the innate immune system, and that a balance between the two determines the outcome of an infection. CA-MRSA strains are associated with high productions of PSM, which is thought to account for the enhanced virulence, easier spreading and severity of infection of CA-MRSA strains compared to hospital-acquired MRSA strains (HA-MRSA) [6,7]. B-type PSM of S. epidermidis are described to play a role in biofilm dispersal [8]

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