Infection characteristics amongSerratia marcescenscapsule lineages

Abstract

ABSTRACTSerratia marcescensis a healthcare-associated pathogen that causes bloodstream infections, pneumonia, and urinary tract infections. The capsule polysaccharide ofS. marcescensis a critical fitness determinant during infection and recent work established the relationship between capsule locus (KL) genetic sequences within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin while theS. marcescenstype strain and other environmental isolates were classified as KL5. In this work, the contribution of these and other capsules to pathogenesis in multiple infection models was determined. Using a murine tail vein injection model of bacteremia, clinical strains demonstrated capsule-dependent colonization of spleen, liver, and kidney following inoculation. The KL5 strain, in contrast, exhibited no loss of survival in this model when capsule genes were deleted. Furthermore, the wild-type KL5 strain was cleared more rapidly from both the spleen and liver compared to a KL1 strain. Similar results were observed in a bacteremic pneumonia model in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to other organs. Finally, strains from each KL clade were tested for the role of capsule in internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains, representing the majority of clinical isolates, exhibited capsule-dependent inhibition of internalization, suggesting that capsule-mediated resistance to macrophage phagocytosis may enhance survival and antibacterial defenses during infection.IMPORTANCEBacterial bloodstream infections result from evasion of the host innate immune system and stable colonization following an initial inoculation event from either an internal or external source. Capsule polysaccharides play a protective role forSerratia marcescensduring bacteremia but there is abundant genetic diversity at the capsule-encoding locus within the species. This study compares the infection characteristics ofS. marcescensisolates belonging to five different capsule types and defines the contributions to infection fitness for each type. By characterizing the differences in capsule dependence and infection potential betweenS. marcescensstrains, efforts to combat these life-threatening infections can be focused toward identifying strategies that target the most critical genetic lineages of this important opportunistic pathogen.