Bacterial Infections and Biomarkers

Bacterial Infections

• Peptidoglycan is the endotoxin found in the cell wall of Gram-negative bacteria
• Medications can target peptidoglycan because they disrupt the cell wall construction
• Transglycosylation forms glycosidic bonds to create the peptidoglycan backbone
• Transpeptidation cross-links the peptidoglycan backbone
• Penicillin-binding proteins (PBPs) are enzymes for the final steps of peptidoglycan synthesis, specifically cross-linking peptidoglycan chains to provide structural integrity
• Penicillin and other 𝛃-lactam antibiotics inhibit PBPs, preventing transpeptidation and transglycosylation, leading to cell lysis and death

Biomarkers for Infection/Inflammation

• C-reactive protein (CRP) is a non-specific acute-phase response to inflammation, infection, and tissue damage
• Elevated CRP levels do not always indicate infection
• Procalcitonin (PCT) elevates in severe systemic inflammations, like sepsis, and have higher specificity than CRP for bacterial infections
• PCT levels are not as elevated in viral infections
• PCT distinguishes between bacterial infections (high PCT) and viral infections (low PCT)

Staphylococcus aureus

• MSSA is sensitive to methicillin and other 𝛃-lactam antibiotics
• MRSA is resistant to methicillin and other 𝛃-lactam antibiotics
• MRSA contains the mecA gene, which prevents methicillin from inhibiting cell wall synthesis
• S. aureus is a Gram-positive cocci arranged in clusters
• Staphylococcus aureus is catalase-positive and breaks down H2O2 into O2 and H20 to survive the killing effect of H2O2 within neutrophils
• Staphylococcus aureus is coagulase-positive and causes plasma to clot
• Staphylococcus aureus infections include skin and soft tissue infections (SSTIs) like folliculitis and boils
• Toxin-associated pathologies include scalded skin syndrome, toxic shock syndrome, and staphylococcal food poisoning
• Serious systemic infections include postsurgical wounds, pneumonia, endocarditis, and sepsis

Streptococcus pneumoniae

• The polysaccharide capsule is the most important virulence factor that protects from phagocytosis and clearance
• The polysaccharide capsule does not activate complement efficiently
• Capsular polysaccharides are antigenic and used to classify pneumococci by serotypes
• Streptococcus pneumoniae are Gram-positive cocci typically arranged in pairs, lancet-shaped
• Streptococcus pneumoniae infections cause pneumonia, bacteremia, and meningitis
• Streptococcus pneumoniae, also know as Pneumococcus, is the most common bacterial etiological agent of community-acquired pneumonia

Streptococcus pyogenes

• Suppurative infections are pus-forming
• Non-suppurative post-streptococcal sequelae are immunologic and occur when antibodies cross-react with normal tissue or form immune complexes that damage normal tissue
• Streptococcus pyogenes are Gram-positive cocci arranged in chains
• M protein is the most important virulence factor and plays a role in adhesion to keratinocytes
• Strains of Streptococcus pyogenes that produce certain M protein types are rheumatogenic and lead to acute rheumatic fever

Atypical Pneumonia

• Mycoplasma pneumoniae lacks peptidoglycan and inflammation-inducing endotoxin making 𝛃-lactams ineffective
• Mycoplasma pneumoniae causes "walking pneumonia” because of its presumed benign nature
• Legionella pneumophila causes headache, muscle pain, chills, gastrointestinal symptoms, and hyponatremia
• Legionella pneumophila is transmitted when aerosolized droplets of the bacteria are inhaled into the lungs
• Reservoirs of Legionella pneumophila are A/C units
• Risk factors for Legionnaires’ Disease include smoking, being immunocompromised, having a chronic lung disease, and being 50 or older

Mycobacterium tuberculosis

• Mycobacterium are called ‘acid-fast’ bacilli because high mycolic acid content in the cell wall makes these organisms resistant to decolorization with acid alcohol
• The primary clinical manifestation is tuberculosis and is transmitted via airborne particles called droplet nuclei
• Latent Tuberculosis Infection (LTBI) means a person harbors Mycobacterium tuberculosis (MTB), but do not have active TB disease and cannot transmit the infection
• Active Pulmonary TB Disease impacts only 5-10% of infected individuals were tubercle overcome the immune system to multiply, spread, and become infectious
• Symptoms of TB include fever, fatigue, lack of appetite, weight loss, persistent cough, hemoptysis (coughing up blood)
• Granuloma formation in tuberculosis contains the infection because TB is an intracellular pathogen
• TB infects alveolar macrophages leading the immune system to form a granuloma to wall off the bacteria
• Granulomas can break down if the immune system weakens due to HIV, malnutrition, or aging, leading to cavitary lesions, bacterial replication and its spread

Pseudomonas aeruginosa

• Pseudomonas aeruginosa are opportunistic human pathogens, often causing nosocomial infections because they do not cause disease in healthy individuals with normal hosts
• Pseudomonas aeruginosa produces pyocyanin (blue-green) and pyoverdin (fluorescein)
• Pyocyanin can color the pus in a wound blue
• Pyoverdin fluoresces under ultraviolet light and detects skin infections in burn patients
• Risk factors for Pseudomonas aeruginosa infections include being a burn victim, being immunocompromised, having cystic fibrosis or if catheterized
• Biofilm formation is a key virulence factor and enables Pseudomonas aeruginosa to cause chronic and persistent infections
• Bacteria within a biofilm are up to 1,000 times more resistant to antibiotics

Chlamydia trachomatis

• Chlamydia trachomatis has a unique biphasic development cycle
• Two forms of the organism occurs; elementary bodies and reticulate bodies
• Elementary bodies initiates infection when attaching to and entering host cells
• Elementary bodies can exist outside of the host cell and resist desiccation
• Elementary bodies bind to receptors on epithelial cells, triggering endocytosis to differentiate into metabolically active reticulate bodies
• Reticulate Bodies rapidly multiplies inside the host cell via binary fission
• Reticulate Bodies reside in a specialized inclusion vacuole to avoid immune detection
• The elementary bodies are then released upon host cell lysis or exocytosis to infect new cells
• Chlamydia trachomatis is primarily transmitted through sexual contact, with the cervix being the most common infection site in women and the urethra in men
• Common symptoms are often asymptomatic
• Chlamydia trachomatis can manifest as mild symptoms, vaginal discharge, dysuria, pelvic pain in women and/or urethral discharge in men
• Complications of chlamydial infection include pelvic inflammatory disease, epididymitis, reactive arthritis, and neonatal conjunctivitis

Viral Infections-Respiratory Syncytial Virus

• The classic illness associate with RSV is bronchiolitis and characterized by cough, wheezing, and dyspnea
• RSV infects the upper respiratory tract and produces giant multinucleate cells (syncytia) via fusion protein
• Risk factors for dangerous RSV infections include chronic lung diseases, heart disease, weakened immune system, a 75 year of age or older, and certain chronic medical conditions

Viral Infections-Influenza

• The three types of influenza viruses include Type A, B, C
• Type A is the only type that is naturally able to infect a range of animal species
• Type B causes major outbreaks
• Type C causes mild respiratory tract infections
• The quadrivalent flu vaccine has 2 - A strains and 2 – B strains
• The influenza virus is an 8 segmented, linear RNA virus
• Hemagglutinin (HA) is the most important virulence factor and binds to host cell receptors
• Neuraminidase (NA) cleaves neuraminic acid to release progeny viruses and also hydrolyzes the protective layer of mucus
• Both Hemagglutinin and Neuraminidase glycoproteins undergo genetic changes, decreasing the effectiveness of the host immune response
• Antigenic drift accumulates changes in the antigenic sites of hemagglutinin and neuraminidase
• Antigenic shift captures a novel hemagglutinin (HA) and neuraminidase (NA) by exchange of genes with another virus in a process called reassortment
• The primary clinical manifestation of influenza virus infection include fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing

Viral Infections-Herpesviruses

• Type of virus of Herpesviruses, outcome of a herpesviruses infection, HSV-1 vs HSV-2 clinical manifestations, Varicella-Zoster virus primary and recurrent differences, Epstein-Barr virus and define where EBV establishes a latent infection, meaning of heterophile-positive mononucleosis, clinical manifestations of infectious mononucleosis

Viral Infections-Hepatitis viruses, HIV and Fungal Infections

• Differences between Hepatitis A, B and C via mode of transmission, outcome, and likelihood of complications
• HBV differences between Dane particles and HBsAg spheres and filaments, general scheme of HCV testing and evaluation
• HIV-1 and HIV-1 replication cycle, antiretroviral treatment, viral load and CD4+ T cell counts, phases of HIV infection, seroconversion, and diseases predictive of progression to AIDS
• Species of Candida albicans, role of pseudohyphae, the clinic manifestations
• Species of Cryptococcus neoformans, structural features important, diseases, AIDS susceptibility
• Type of species and diseases of Aspergillus, clinical manifestations and risk factors