Bacteriology+II+-+PID+Dr.+Gutierrez.pdf

Principle of Infectious Diseases Bacteriology II: Virulence and pathogenicity Fungal infections Dr. Ricardo Gutiérrez, Microbl., MSc, Ph.D. Assistant Professor [email protected] Summer semester, 2024 Section 4. Bacterial virulence infectious...

Principle of Infectious Diseases Bacteriology II: Virulence and pathogenicity Fungal infections Dr. Ricardo Gutiérrez, Microbl., MSc, Ph.D. Assistant Professor [email protected] Summer semester, 2024 Section 4. Bacterial virulence infectious Reservoir suscept routes Moffman Host Section 4. Bacterial virulence Key concepts Pathogenicity Pathogenesis Reservoir ability to cause disease biological mechanisms natural source of the that lead to a disease pathogen Virulence Virulence factors Pathogenicity islands measurement of bacterial characteristics Organized group of pathogenicity that contribute to virulence genes coding for virulence factors Section 4. Bacterial virulence Establishment of the infection EXPOSURE ADHESION INVASION COLONIZATION Potential outcomes: Commensal interaction Mutualistic relationship Disease Invasive strains… Disease occurred Section 4. Bacterial virulence Stages of the infection Haitiffing exposure thetimeperiodbeforeinfection thebacteriaisshedbyindividual path.mg fdateYituttn Einserved Eaitsi9 r Section 4. Bacterial virulence Infection outcomes No colonization exposureonly colonizeddisease Infection → disease → recovery Infection → subclinical disease thisisoutcome heiscarrier remember Infection → disease → death/disability Infection → disease → persistence (carriers) Section 4. Bacterial virulence Disease carriers Incubatory carrier: carrier that is incubating the pathogen but not yet ill (can be shedding of pathogen) Convalescent carrier: those who are recovering (no clinical signs) but continue shedding the pathogen Persistent carrier: the animal recovered from the disease, but could not eradicate the pathogen Healthy carrier (subclinical): carrier state without clinical symptoms but shed the pathogen Clinical carrier: infectious animal with a clinical infection in a peracute, acute or chronic phase. Incubatory carrier Clinical infection Exposed Acute phase individual Recovered (clinical sigs) Convalescent carrier individual Healthy carrier Persistent or chronic carrier Section 4. Bacterial virulence Disease carriers Example Streptococcus suis in pigs: Common colonizer of the upper porcine respiratory tract Almost 100% of pig farms are seropositive Tonsils of healthy pigs are natural niche where the pathogen can survive and hide from the immune system It can breach the epithelial barrier leading to invasive disease in its natural host Can cause pneumonia, arthritis, meningitis, as well as septicemia Host niches and infection sites of S. suis in the pig Section 4. Bacterial virulence Disease carriers Detection of convalescent carriers! Example “Strangles in horses”: Streptococcus equi subsp. equi (not a commensal) Highly contagious febrile disease involving upper respiratory tract with abscessation of regional lymph nodes in equines FOLLOW UP: 3 negative culture at weekly intervals Section 4. Bacterial virulence Virulence factors Bacterial traits that confer pathogenicity. Virulence factors enable processes such as adhesion, biofilm formation, motility, toxin secretion, immune evasion, colonization, and bacterial cell–cell communication. Allowing bacteria to colonize (extracellular and/or intracellular) niches in hosts and produce disease. Section 4. Bacterial virulence Virulence factors Surface-associated proteins Host cell adhesion and colonization Nutrient acquisition Cell invasion and immune evasion Quorum-sensing Biofilm formation Bacterial cell-cell communication Virulence gene expression control Pili Adhesion Toxin production DNA uptake Tissue damage Invasion Flagella DNA transfer Impairs immune response Motility Motility Host cell adhesion Efflux pumps Antibiotic secretion Two component system Siderophore secretion Virulence factor regulation Other secretion of toxin compounds LPS Inflammation Secretion systems Tissue Virulence factor delivery damage Protein secretion and transport DNA uptake and transfer Section 4. Bacterial virulence Highlighted virulence factors: Exotoxins Intracellular Exo → secreted by the bacteria. Translocated delivered Intracellular targets toxins Exotoxins are highly antigenic proteins. toxins They are different types of exotoxins classified according to the mechanisms and targets. Membrane- Cell-surface damaging Cell-surface targets active toxins toxins Extracellular matrix (EM) toxins EM targets Section 4. Bacterial virulence Highlighted virulence factors: Translocated Intracellular toxins delivered toxins Exotoxins Intracellular targets They usually modulate the host cell metabolism Translocated toxins: AB toxins Intracellular delivered: T3SS toxins Section 4. Bacterial virulence Highlighted virulence factors: Exotoxins Intracellular targets They usually modulate the host cell metabolism or produce cell death AB toxins Type III Secretion System toxins Enterotoxin LT Shiga toxin proteins Yahtffduce die also Section 4. Bacterial virulence Highlighted virulence factors Toxins produced by endospore-forming bacteria n n n Section 4. Bacterial virulence Highlighted virulence factors Endospores & toxins Anthrax, bovine carcass Photograph of an anthrax-infected bovine carcass. Note the marked bloating. Bacteria in body fluids exuded from orifices after death form spores that contaminate nearby soil and vegetation Section 4. Bacterial virulence Highlighted virulence factors: Membrane- damaging toxins Exotoxins Membrane-damaging toxins They are cytotoxic (kills the cell) dissolve likedetergents lipids Pore-forming toxin Lipase secreted toxins Section 4. Bacterial virulence Highlighted virulence factors: Cell-surface active toxins Exotoxins Cell-surface active toxins Attached to a cell receptor and activate second messenger pathways. Disturbance of metabolic pathways Superantigens (a type of “cell-surface active toxins”) Trigger excessive stimulation of T lymphocytes. Resulting in massive T-cell proliferation and cytokine release. Fever, arthritis, dermatitis, shock. Type I Exotoxin Cell-surface active Disturbance of cell metabolism e.g., Clostridium perfringens Section 4. Bacterial virulence Highlighted virulence factors: Cell-surface active toxins Exotoxins Cell-surface active toxins Attached to a cell receptor and activate second messenger pathways. Disturbance of metabolic pathways Superantigens (a type of “cell-surface active toxins”) Trigger excessive stimulation of T lymphocytes. Cytokines Resulting in massive T-cell proliferation and cytokine release. Fever, arthritis, dermatitis, shock. Section 4. Bacterial virulence Highlighted virulence factors: Extracellular matrix (EM) toxins Exotoxins Extracellular matrix toxins EM : substances or environment between and below cells. Toxins allow free-movement of bacteria Hyaluronic acids Collagen Hyarunidases Collagenases Streptokinase Section 4. Bacterial virulence Highlighted virulence factors: LPS (endotoxin) exposed tooutsideenvironment LPS has diverse immunostimulatory and procoagulant effects. LPS induces signaling and immune dysregulation. Lipid A component = endotoxin. The key recognition receptor is Toll-like receptor 4 (TLR4) Section 4. Bacterial virulence The intravascular release or presence of LPS present massive effects on the hosts, and their impact is concentration dependent. High endotoxin levels can cause shock and intravascular coagulation. Septic shock syndrome (endotoxic shock): Critical reduction in tissue perfusion & acute failure of multiple organs Endotoxin in small amounts can induce symptoms of inflammation, fever, and leukopenia, and damage to blood vessels, finally leading to hypotension. Section 4. Bacterial virulence Highlighted virulence factors: Siderophores Iron uptake Vertebrate tissue is virtually devoid of free iron Iron is essential for bacterial growth Siderophores Bacterial cytotoxins damage host cells -> release of ferritin, hemoglobin, lactoferrin Receptor-mediated recognition Ironalreadyin inbody Section 4. Bacterial virulence Highlighted virulence factors: Pili/Fimbriae Their presence greatly enhances the bacteria's ability to attach to the host, colonize and establish infection. E.coli F4+ fimbriae =Neonatal piglets Section 4. Bacterial virulence Highlighted virulence factors: Capsule Only in some bacterial species Capsule Polysaccharide layer (glycocalyx) Semi-rigid border Functions: Protection (environment, phagocytosis) Virulence factor (adherence) Nutrient reserve Section 4. Bacterial virulence previous Q usedforVP Highlighted virulence factors: hecovered asked wordcapsule ustoidentifyf xthatwascovered Capsule The capsule can protect the bacteria from being neutralized or killed by the immune system. Example: encapsulated strains of Streptococcus are more virulent than nonencapsulated strains and are more likely to invade the bloodstream and cause septicemia and meningitis Section 4. Bacterial virulence Capsule Streptococcus capsule revealed by India Ink Section 4. Bacterial virulence alsoprevious usedforVP Q Highlighted virulence factors The regulation in gene expression in response to fluctuations in cell Quorum-sensing population density, mediated by chemical signal molecules (autoinducers) When the bacterial population reaches a defined density (a bacterial quorum), the pheromones attain a critical threshold concentration at which they coordinate expression of bacterial genes, so that the colonizing bacteria act as a community rather than as individuals Section 4. Bacterial virulence QforVP alsoprevious prettysure Highlighted virulence factors Flagella Motility Adhesion Participates in biofilm formation Modulate immune system of eukaryotic cells Section 4. Bacterial virulence Biofilm Clusters of bacteria that are attached to a surface and/or to each other and embedded in a self-produced matrix Consists of substances like proteins, polysaccharide and released DNA Functions: Protection from immune system Protection from desiccation Protection from antibiotics Improved acquisition of nutrients Improved bacterial-bacterial interactions Section 4. Bacterial virulence Biofilms Section 4. Bacterial virulence hesaidhewon'tevaluateusonthisslide Transfer of virulence factors (VF) a. Transformation. Bacteria acquire free DNA from the environment. Some of the acquired DNA may be VF genes. b. Transduction. Bacteriophages (viruses of bacteria) transfer bacterial DNA from one bacterium to another. Some of the transferred DNA may be VF genes. c. Conjugation. One bacterium can transfer a plasmid (mobile DNA) to another bacterium. Usually, plasmids contain VF genes. Section 4. Bacterial virulence Transfer of virulence factors (VF) Emergence and dissemination of Antimicrobial drug resistance Selection of serious pathogenic strains in the clinics Section 5. Fungal infections Pathogens Section 5. Fungal infections Fungi Overview Eukaryotic Non-photosynthetic heterotrophs: produce exoenzymes to obtain nutrients by absorption Widely distributed in the environment Fungi grow aerobically and many are strict aerobes Cell membrane contains sterols (ergosterol) Cell wall with chitin, glucan and mannoproteins Vast majority are saprophytes and non-pathogens Store their food in the form of starch. Reproduce both sexually (spores) and asexually (spores, budding or fragmentation) Resistant to classical antimicrobial drugs (many natural antibiotics originated from fungi) Section 5. Fungal infections Fungal structure Single-celled or multicellular organisms. Almost all the fungi have a filamentous structure except for yeasts. Filamentous structure are long thread-like structures called hyphae. Many hyphae together form a mesh-like structure called mycelium. Unicellular yeasts: round single cells characterized by budding Membranous organelles The nucleus is dense, clear, with chromatin threads. The nucleus is surrounded by a nuclear membrane Non-motile. Section 5. Fungal infections Section 5. Fungal infections Section 5. Fungal infections Mycoses Pathogenic fungi establish infection in apparently normal hosts, regarded as primary systemic mycoses. Opportunistic fungi are more likely to establish infection in an immunosuppressed host, but this is not a prerequisite to infection in animals. Thoracic histoplasmosis, Prolonged administration of antimicrobials or immunosuppressive radiograph (lateral), dog agents main predisposing factor for opportunistic fungal infections The soil reservoir is the primary source of most infections, which can be acquired by inhalation, ingestion, or traumatic introduction of fungal elements. Certain fungi are ubiquitous; others are more regionally specific. Treatment is prolonged in all cases. Nasal aspergillosis, gross lesions, dog Section 5. Fungal infections Mycoses