Pathogenic Bacteriology Lecture Notes - Secretion Systems and Pathogenesis

Course Information

  • Course Name: MICR4110 / 6110 Pathogenic Bacteriology

  • Lecture Date: January 20, 2026

  • Lecture Focus: Secretion Systems - Delivery of Virulence Factors, Movement, and Adhesion

Reminders and Due Items

  • Paper Q&A #2: Due FRIDAY, Jan. 23

  • Discussion Post #3: Due MONDAY, Jan. 26

Stages of Bacterial Pathogenesis

  • Overview of bacterial colonization and survival mechanisms in a host (Table 11-1).

    • Virulence Factor/Strategy:

    • Biofilm formation

    • Motility and chemotaxis

    • Siderophores

    • Iron abstinence

    • Transition metal ion uptake and efflux

    • Capsules

    • Lengthened and shortened LPS O antigen

    • sIgA proteases

    • C5a peptidase

    • Pili and fimbriae

    • Nonfimbrial adhesions

    • Binding to M cells

    • Variation in surface antigens

    • Invasins

    • Actin rearrangements in the host

    • Catalase and superoxide dismutase

    • Elastase and other proteases

    • Nucleases

    • Toxic proteins (toxins)

    • Function:

    • Establish surfaces for adhesion and formation of multilayered bacterial communities;

      • Benefits: Reduced susceptibility to antibiotics, continuous dissociation and dissemination through the body.

    • Motility strategies (reaching mucosal surfaces, especially in high-flow regions).

    • Mechanisms for iron acquisition induced by the need for iron-binding proteins.

    • Polyfunctional strategies that include host immune evasion, promoting cellular invasion, altering cellular signaling, and inducing apoptosis in phagocytic cells.

Survival Mechanisms in External Environment

  • Bacteria must adapt before infecting a host.

    1. Endospore Formation:

    • Protective coats for survival in harsh conditions (Clostridium sp., Bacillus sp.).

    1. Host Cell Parasitism or Vector:

    • Example: Legionella pneumophila leading to Legionnaire’s disease.

    1. Secondary Metabolites:

    • Antibiotics, bacteriocins, antimicrobial peptides; along with their counter-adaptive mechanisms like antibiotic resistance.

    1. Biofilm Formation:

    • Extracellular polysaccharide structures that adhere to abiotic surfaces and contribute to community robustness.

Host Barriers and Colonization

  • Host defenses include skin and mucin layer, which provide significant barriers to bacterial entry.

    • Role of Mucin:

    • A complex layer of glycoproteins and polysaccharides acting as a lubricant and barrier to bacterial colonization.

Flagella and Bacterial Movement

  • Flagella Structure and Function:

    • Long helical structures extending from surface, composed of flagellin (rigid protein).

    • Basal body serves as motor; powered by proton motive force.

  • Flagella arrangements vary among species:

    • Polar Flagella:

      • Mono- or lophotrichous in dilute solutions.

      • Examples: Pseudomonas aeruginosa, Vibrio cholerae.

    • Peritrichous Flagella:

      • Numerous, favor movement in viscous environments.

      • Examples: E. coli, Salmonella enterica, Proteus mirabilis.

  • Example of Vibrios:

    • Different flagellar systems for differing environments (e.g., Vibrio parahaemolyticus).

Stages of Bacterial Infection

  1. Colonization:

    • Germination, attachment, invasion, evasion.

  2. Persistence:

    • Acquiring nutrients, multiplying, evasion.

  3. Spread:

    • Movement within the host and transmission to new hosts.

Secretion Systems Overview

  • Transport of cell proteins is central to bacterial virulence, contributing to the delivery of virulence factors.

  • Types of secretion systems:

    • General Sec system, SRP System, TAT System.

    • T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, and Accessory Sec System.

    • Sortase Systems unique to proteins needed for virulence.

General Sec System

  • Key points:

    1. Signal peptide essential for secreted pathways (10-12 hydrophobic residues, about 2 charged AA's).

    2. SecB chaperone binds unfolded protein until reaching SecA.

    3. Binding to SecYEG for transport through the membrane is vital.

SRP System

  • Used primarily for polytopic proteins during translation.

    • Process includes SRP binding to signal during translation and directing to the membrane receptor protein, FtsY.

Accessory Sec System

  • Some Gram-positive bacteria utilize this for protein transportation, specifically serine-rich glycosylated proteins.

Twin-Arginine Transport (TAT) System

  • Handles the transport of fully folded proteins:

    • TAT signal recognized by TatABC translocase with the formation of a pore complex.

Gram-negative Secretory Systems

  • Systems to facilitate protein transportation across the outer membrane.

    • Sec-dependent methods (T2SS, T5SS) and Sec-independent methods (T1SS, T3SS, T4SS, T6SS).

T2SS Mechanism

  • Involves complex proteins forming a channel in the outer membrane with a pseudopilus. - Related mechanisms seen in T4 pili and archaeal flagella.

Autotransporters and T5SS

  • Many virulence factors considered autotransporters.

    • Functions through a substantial precursor protein with assembled domains and a known linker region.

T1SS Mechanism

  • Works through a 3-protein complex, directly secreting through relevant cellular membranes.

  • Example in E. coli involves a specialized ABC transporter.

T3SS: Contact-Dependent Transport

  • Also known as