Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

Abstract

Background: Staphylococcus epidermidis (se) is an important cause of late-onset sepsis in neonates. se frequently produces a polysaccharide intercellular adhesin (PIa) biofilm, important in the pathogenesis of these infections. Little is known about how the neonatal innate immune system reacts to se biofilm-associated infections. Our hypothesis was that se biofilms induce a lower complement activation in neonates as compared with adults. Methods: cord blood from term infants (n = 15) and blood from adults (n = 6) were studied in an ex vivo whole-blood sepsis model. a PIa biofilm-producing strain (se1457) and its isogenic mutant (M10), producing a non-PIa biofilm, were used. results: Both se biofilms induced stronger complement activation in adult than in cord blood (P ≤ 0.033). We found lower levels of antibodies toward both PIa (P = 0.002) and the whole bacterium (P = 0.001) in cord vs. adult blood. By contrast, the interleukin-8 (IL-8) and IL-6 secretion were higher in cord than in adult blood (P ≤ 0.002). The PIa biofilm induced stronger complement activation than the non-PIa biofilm. conclusion: We conclude that the neonatal complement system exhibits a maturational deficiency. This may reduce the ability of neonates to combat biofilm-associated se infections. Staphylococcus epidermidis (SE) is the most prevalent pathogen causing late-onset sepsis in neonates (1). These infections are seldom lethal, but they cause significant morbidity, especially in preterm infants (1,2). SE infections are often associated with biofilm production on the surface of foreignbody implants (3,4). Biofilms are adherent multicellular bacterial aggregates embedded in a self-produced extracellular matrix. The best-described matrix compound in SE biofilms is a β-(1,6)-linked N-acetylglucosamine named polysaccharide intercellular adhesin (PIA) (5,6).SE and SE biofilms interfere with the host immune response at different levels. PIA biofilms inhibit the action of antimicrobial peptides (7), decrease neonatal inflammatory response (8), and decrease phagocytosis and degranulation by neutrophils (7). Biofilms may "decoy" antibodies and complement on the bacterial surface and thereby decrease opsonization and phagocytosis (9-11). The ability of biofilm-producing bacteria to avoid immune clearance and the general immaturity of the neonatal immune system (12) are postulated to increase the risk of neonatal SE sepsis (13). As compared with adults, neonates have a lower quantitative and qualitative complement activation (14,15), reduced upregulation of cellular response (12), and an immature cytokine response pattern (16)(17)(18)(19). Preterm infants demonstrate a markedly reduced capacity to upregulate oxidative burst in leukocytes in response to SE (20). However, some authors have reported that SE may induce a similar proinflammatory cytokine response in neonates and adults (19,21), indicating a differential maturation of various parts of the neonatal innate immune system. Differences in maturation have also been described when challenging t...

Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a

“…Purified PIA from S. epidermidis has previously been identified as modulating complement binding and activation in opsonised human neutrophils (Kristian et al, 2008), whole blood (Fredheim et al, 2011), human serum (Satorius et al, 2013) and neonatal whole blood (Granslo et al, 2013). Our data is consistent and extends these findings demonstrating that PIA may disintegrate from or for a 'bridge' between the bacterial biofilm leukocytes which is consistent with inhibition of opsonisation shown previously (Kristian et al, 2008).…”

“…More specifically, staphylococcal biofilm matrices have been implicated in complement activation. Here PIA from S. epidermidis has been shown to modulate complement binding and activation in opsonised human neutrophils (Kristian et al, 2008), and induction of complement C5a has been demonstrated in whole blood (Fredheim et al, 2011), human serum (Satorius et al, 2013) and neonatal whole blood (Granslo et al, 2013).…”

Host Response to Staphylococcus epidermidis Colonization and Infections

“…Deficiencies in complement factor C3 and IgG are associated with a higher risk of neonatal CoNS-associated sepsis (Lassiter et al, 1991). Furthermore, in a study using an ex-vivo whole-blood sepsis model, S. epidermidis induced significantly lower complement activation in neonatal compared to adult blood (Granslo et al, 2013). This finding suggests that there is a maturational deficiency in the neonatal complement system, which, in part, may explain why neonates are more susceptible to S. epidermidis septic infections than adults.…”

Neonatal Immune Adaptation of the Gut and Its Role during Infections

“…The polysaccharide intercellular adhesin (restricted to a subpopulation of Staphylococci epidermidis ) and the poly-g-DL-glutamic acid (ubiquitous among Staphylococci epidermidis strains) protect the bacteria against cathelicidin and human β -defensin 3 [147, 148]. Moreover, the immaturity of the neonatal complement system impairs the capacity of neonates to fight against biofilm-associated Staphylococci epidermidis infections [149]. Interestingly, a study, dealing with the effects of lactoferrin with antibiotics commonly used in neonatal practice against CoNS, shows a synergic action, demonstrating that lactoferrin may be a promising agent to improve treatments of NS caused by CoNS [150].…”