Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from salmonella minnesota S218 without causing bacterial death

Abstract

It has been recognized since 1895 (1) that some gram-negative bacteria are sensitive to the lytic action of fresh serum, whereas others are highly serum resistant. In general, serum-resistant organisms are more pathogenic than serum-sensitive bacteria in animal models of infection, and serum-resistant organisms are more commonly isolated from the bloodstream of patients with gram-negative bacteremia (2). In attempts to define the basis of this important virulence factor, characteristics of the outer membrane of serum-sensitive and serum-resistant organisms have been analyzed and compared (3)(4)(5). The presence of a complete lipopolysaccharide (LPS) 1 (i.e., the smooth phenotype) is the characteristic most clearly associated with serum resistance. Rough bacteria lacking a complete LPS are almost invariably serum sensitive.The antibody and complement requirements for serum killing of bacteria also have been examined. It has been shown (6-8) that killing of gram-negative bacteria by serum requires the participation of terminal components of the complement system ((25-9). However, the mechanism of resistance of gram-negative bacteria to serum killing in the presence of adequate antibody is still unknown.Resistance to serum killing could involve the inability to form a membrane attack complex on the organism. An alternative hypothesis, however, is that a membrane attack complex that forms on the bacterial surface may be functionally impotent either because of failure to insert into the bacterial outer membrane or because the inserted complex does not cause damage to vital outer or inner membrane structures.Previous studies have examined a number of aspects of this issue. Studies have suggested that serum-sensitive and serum-resistant strains of Escherichia coli (9, 10) or Salmonella typhimurium (11) have equivalent amounts of C3 deposited. It is not resolved whether (25 is deposited on serum-resistant bacteria. Reynolds et al. (11) could not demonstrate deposition of functional C5 on serum-resistant S. typhimurium in Mg ++ saline after incubation in C6-deficient rabbit serum. On the other hand, Ogata and Levine (10) demonstrated equivalent (25 consumptior~ by strains of E. coli that varied in complement sensitivity; however, evidence for levels of cell-bound (25 was not 1 Abbreviations used in this paper: CFU, colony-forming unit; HBSS, Hanks' balanced salt solution; LPS, lipopolysaccharide; PNHS, pooled normal human serum; RT, room temperature. J. Exp. MED.

Absent Bactericidal Activity of Mouse Serum against Invasive African Nontyphoidal Salmonella Results from Impaired Complement Function but Not a Lack of Antibody

“…These findings suggest that differences exist between the susceptibility of erythrocytes and Salmonella to the lytic/ bactericidal effects of mouse complement, with Salmonella being more resistant than erythrocytes. Complement that does not insert into the Salmonella outer membrane can be shed from the surface of S. Minnesota (26,27), and various molecules on the Salmonella surface, including those encoded by rck (28), traT (29), and pgtE (30), confer some degree of resistance to complement-mediated killing.…”

The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children

“…In the 1980s, Joiner showed that when complement membrane attack complex forms on lipopolysaccharide on the surface of salmonellae, it can be cleaved off (37) and thus fail to insert into the bacterial outer membrane (38). In addition, rck is associated with abnormal polymerization of C9 in the membrane attack complex (39).…”

Human Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella

“…Long-chain LPS has been shown to confer resistance by promoting the deposition of complement components at a distance from the outer membrane, thus allowing the MAC to be shed from the bacterial surface without disrupting membrane integrity (3,4). The PhoPPhoQ-regulated gene pagC has been shown to confer resistance when expressed in both E. coli and S. enterica Choleraesuis by a currently uncharacterized mechanism (5).…”