Table 1.
Examples of bacterial virulence factors important during the molecular pathogenesis of BSI and sepsis
| FACTOR | ORGANISM | FUNCTION | REF. |
|---|---|---|---|
| Colonization/Adherence | |||
| RlrA, type IV pili, type I pili | S. pneumoniae, K. kingae, E. coli | Adherence to epithelial cells like nasal, respiratory, and bladder cells, respectively | 19, 93, 16 |
| NanA | S. pneumoniae | Desialidation of LPS of H.influenzae and N. meningitidis, exposing them to host recognition and decreasing their biofilm-forming capacity | 22, 23 |
| Epithelial Damage/Transcytosis | |||
| LPS | gram-negative bacteria | Produces gut-barrier dysfunction mediated by HMGB1 and the release of mast cell proteases causing increased bacterial translocation | 38, 39 |
| ExoU/ExoT | P. aeruginosa | TTSS effectors that cause acute epithelial damage through apoptosis, producing access to deeper tissue | 41, 94 |
| Hek | E. coli | Adherence and invasion into colonic epithelial cells in vitro | 36, 37 |
| Intracellular Survival | |||
| MntH | Salmonella sp. | Manganese transport; Inhibition of oxidative killing resulting in intracellular replication | 88 |
| Protein M | S. pyogenes | Selective inhibition of azurophilic granules with the phagosome | 64, 65 |
| Complement Inhibitors | |||
| Pht/Psp proteins | S. pneumoniae | Mucosal colonization, cleavage of complement protein C3, and promotion of translocation from sites of colonization | 29, 30 |
| C5a peptidase | S. pyogenes | Cleavage of complement protein C5a, a potent chemoattractant molecule | 70 |
| Polysaccharide capsule | GBS, E. coli | Inhibition of C3b deposition, limiting opsonization through the macrophage receptor CR1 | 73 |
| Innate Immunity Effectors | |||
| Protein A | S. aureus | Binding to Fc portion of IgG, masking itself in incorrectly oriented antibody | 59, 60 |
| AdsA | S. aureus, E. faecalis, S. pyogenes, S. epidermiditis | Synthesis of adenosine, which engages receptors on the surface of leukocytes that inhibit proinflammatory responses | 53–56 |
| IgA protease | N. meningitides, U. urealyticum | Cleavage of IgA, avoiding a neutralizing antibody response | 26–28 |
| Tcps, TlpA | UPEC, S. enterica | Inhibitory mimics of the TLR/Interleukin-1 (TIR) receptor domain to impair TLR signaling, inducing host cell apoptosis and downregulate proinflammatory signals | 49, 50 |
| LPS | gram-negative bacteria | Heighten inflammatory response through TLR4, leading to increased BT | 38, 46, 47, 39 |
| Peptidoglycan, lipoproteins | gram-positive bacteria | Proinflammatory signaling through TLR2, inducing host cell apoptosis | 48 |
| Polysaccharide capsule | S. pneumoniae, N. meningitides, E. coli, GBS | Direct inhibition of phagocytosis; block Siglecs (sialic acid capsule), dampen proinflammatory responses and suppress phagocytosis; act as an antimicrobial peptide ’sink’ | 58, 61–63, 74 |
| Adaptive Immunity Effectors | |||
| n-butyrate synthesis | E. coli, | Inhibit the maturation of monocyte-derived DCs and expression of cytokines by macrophages and DCs in response to LPS | 82, 83 |
| CflA/CflB | S. aureus | Antigenic disguise by precipitate and clot host fibrin on the surface of the bacterium | 75, 76, 77 |
| Omp proteins | N. meningiditis | Antigenic variation of outer membrane proteins disguises host antibody targets | 78, 79 |
| SAgs | S. aureus, S. pyogenes | Non-specific proliferation of T helper cells due to cross-linking of MHCII molecule and T cell receptor | 95, 59 |
| Nutrient Acquisition | |||
| IroN | E. coli, Salmonella sp., S. aureus | Scavenge and transport iron from host hemoproteins; necessary for bacterial growth | 86, 87 |
| ZnuABC | Salmonella sp., S. pneumoniae | High affinity zinc transport system; necessary for full virulence in mice; proteins regulates complement inhibiting | 30, 89 |
NOTE.
Abbreviations. HMGB1, inflammatory cytokine high-mobility group box 1; TTSS, type III secretion system; IgG, immunoglobulin G; IgA, immunoglobulin A; UPEC, uropathogenic E. coli; TLR, Toll-like receptor; DC, dendritic cell; CflA/B, clumping factor A/B of S. aureus; SAgs, superantigens; MHCII, major histocompatability complex II; IroN, bacterial siderophore. This table summarizes bacterial virulence factors described during this review, but is not intended to be a comprehensive list of all bacterial factors involved in the pathogenesis of sepsis.