Vaccine potential of poly-1-6 beta-D-N-succinylglucosamine, an immunoprotective surface polysaccharide of Staphylococcus aureus and Staphylococcus epidermidis

Staphylococcus aureus and S. epidermidis are among the most common causes o f nosocomial infection, and S. aureus is also of major concern to human hea lth due to its occurrence in community-acquired infections. These staphyloc occal species are also major pathogens for domesticated animals. We have pr eviously identified poly-N-succinyl beta-1-6 glucosamine (PNSG) as the chem ical form of the S. epidermidis capsular polysaccharide/adhesin (PS/A) whic h mediates adherence of coagulase-negative staphylococci (CoNS) to biomater ials, serves as the capsule for strains of CoNS that express PS/A, and is a target for protective antibodies. We have recently found that PNSG is made by S. aureus as well, where it is an environmentally regulated, in vivo-ex pressed surface polysaccharide and similarly serves as a target for protect ive immunity. Only a minority of fresh human clinical isolates of S. aureus elaborate PNSG in vitro but most could be induced to do so under specific in vitro growth conditions. However, by immunofluorescence microscopy, S. a ureus cells in infected human sputa and lung elaborated PNSG. The icn genes , previously shown to encode proteins in CoNS that synthesize PNSG, were fo und by PCR in all S. aureus strains examined, and immunogenic and protectiv e PNSG could be isolated from S. aureus. Active and passive immunization of mice with PNSG protected them against metastatic kidney infections after i ntravenous inoculation with eight phenotypically PNSG-negative S. aureus. I solates recovered from kidneys expressed PNSG, but expression was lost with in vitro culture. Strong antibody responses to PNSG were elicited in S. au reus infected mice, and a PNSG-capsule was observed by electron microscopy on isolates directly plated from infected kidneys. PNSG represents a previo usly unidentified surface polysaccharide of S. aureus that is elaborated du ring human and animal infection and is a prominent target for protective an tibodies. (C) 2000 Elsevier Science B.V. All rights reserved.