Bacterial Structure, Virulence Factors & Spores

The cell envelope

Peptidoglycan. The wall is one giant mesh: glycan chains of alternating N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG), with a short peptide on each NAM ending in D-Ala-D-Ala. Transpeptidases, the penicillin-binding proteins (PBPs), cross-link neighboring peptides so the wall withstands osmotic pressure. Human cells lack peptidoglycan, making it an ideal drug target: β-lactams acylate PBPs and vancomycin binds D-Ala-D-Ala. Lysozyme in tears and saliva cleaves the β-1,4 bond between NAM and NAG.

LTA vs LPS. Lipoteichoic acid (via TLR2) and lipid A (via TLR4 with CD14) both induce IL-1, IL-6 and TNF-α, but only LPS is true endotoxin, driving fever, shock and DIC in gram-negative sepsis.

Capsules and encapsulated organisms

Structure and function. Capsules are usually polysaccharide (hyaluronic acid in group A strep, polyribosylribitol phosphate in Hib, sialic acid in group B strep and E. coli K1); Bacillus anthracis alone has a poly-D-glutamate capsule. By blocking C3b deposition and phagocyte grip, the capsule is often the key virulence factor. In the quellung reaction, type-specific antiserum makes the capsule swell and become visible.

Asplenia. S. pneumoniae, H. influenzae type b, N. meningitidis, E. coli K1, Salmonella Typhi, Klebsiella and group B strep are cleared by opsonizing antibody plus splenic macrophages. After splenectomy or sickle cell autosplenectomy, infection can become fulminant sepsis within hours; patients need pneumococcal, Hib and meningococcal vaccines, and Howell-Jolly bodies on the smear mark the missing spleen.

Conjugate vaccines. Polysaccharides are T-independent antigens: mostly IgM, little memory and weak responses before age 2. Coupling them to a protein carrier (tetanus or diphtheria toxoid) lets polysaccharide-specific B cells present carrier peptides on MHC II to helper T cells, yielding class-switched IgG and memory, which is why Hib, pneumococcal conjugate and meningococcal ACWY vaccines work in infants.

Adhesion, motility and biofilm

• Pili (fimbriae) mediate adherence, such as the P fimbriae of uropathogenic E. coli in pyelonephritis. The sex pilus bridges two cells for conjugative DNA transfer. Gonococcal pili undergo antigenic variation, so antibody fails and reinfection is common.
• Flagella drive motility and carry the H antigen used in serotyping (E. coli O157:H7).
• Biofilm is a self-made polysaccharide matrix that shields bacteria from antibiotics and phagocytes: S. epidermidis on catheters and prosthetic joints or valves, viridans streptococci (dextran) on damaged heart valves, S. mutans in dental plaque, and mucoid P. aeruginosa (alginate) in cystic fibrosis lungs. Device infections often require hardware removal.

Endospores

Formation. When nutrients run out, the gram-positive rods Bacillus and Clostridium form endospores: dormant bodies with a dehydrated core rich in calcium dipicolinate and a keratin-like coat. They resist heat, drying and disinfectants, persist in soil for years and germinate when conditions improve. Spores start anthrax, B. cereus food poisoning from reheated rice, tetanus, infant botulism (honey) and C. difficile colitis.

Alcohol hand rubs do not kill C. difficile spores: wash hands with soap and water and clean surfaces with a sporicidal agent such as bleach.

Virulence proteins and the growth curve

Defeating antibody and phagocytes. S. aureus protein A binds the Fc of IgG, so the antibody cannot opsonize or fix complement. IgA protease from S. pneumoniae, H. influenzae and Neisseria cleaves mucosal IgA1. Group A strep M protein resists phagocytosis by limiting C3b deposition and mimics cardiac myosin, the basis of rheumatic fever.

Type III secretion. A needle-like injectisome delivers effector proteins straight into host cytoplasm: Salmonella and Shigella remodel actin to force their own uptake, EPEC and EHEC build attaching-and-effacing pedestals, Yersinia Yops paralyze phagocytes, and Pseudomonas injects cytotoxins.