Panton Valentine leucocidin enhances community-acquired methicillin-resistant Staphylococcus aureus colonization of the gut

Abstract

ObjectiveCommunity-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) independently emerged and became epidemic at the end of the 20th century. Since gut carriage was reported for CA-MRSA and since the common feature of historical CA-MRSA is to harbour Panton Valentine leucocidin (PVL), the question of the possible involvement of this toxin in gut carriage was investigated in mice and cellular models. MethodsCA-MRSA of three lineages (USA300, USA1100, and ST80) and their isogenic {Delta}pvl derivatives, were tested in competition for gut colonisation in mice and in a model of bacterial adhesion to mucus-producing intestinal epithelial cells. ResultsMice inoculated with CA-MRSA and their {Delta}pvl derivatives had their gut successfully colonised by the three lineages regardless of the presence of PVL; however, the wild type (WT) CA-MRSA outcompeted the {Delta}pvl derivatives by at least 3 log after 40 days for all lineages tested. In vitro competition of CA-MRSA with their {Delta}pvl derivatives showed no fitness disequilibrium after 6 weeks, ensuring that the results obtained in mice did not result from direct bacterial interference. Direct fluorescence assay of mice intestine showed S. aureus localised at the mucosal surface of the intestine and within the intestinal crypts, but not within epithelial cells, suggesting a bacterial tropism for the mucus layer. Significant difference in adhesion to intestinal epithelial cells between WT and pvl knockout was only observed on mucus-producing cells, and not on non-producing ones. ConclusionPVL enhances CA-MRSA gut colonisation in mice by a mechanism involving adhesion-colonisation of the mucus layer.