Spirochaetales - Bacteria and Disease PDF

**Spirochaetales** - Gram-negative spirochetes - Spirochete from Greek for "coiled hair" - Extremely thin and can be very long - Motile by periplasmic flagella (axial fibrils or endoflagella) reside inside the cell within the periplasmic space **Taxonomy** - Order: Spirochaetales...

**Spirochaetales** - Gram-negative spirochetes - Spirochete from Greek for "coiled hair" - Extremely thin and can be very long - Motile by periplasmic flagella (axial fibrils or endoflagella) reside inside the cell within the periplasmic space **Taxonomy** - Order: Spirochaetales - Family: Spirochaetaceae - Genus: - *Treponema* - *Borrelia* - Family: Leptospiraceae - Genus: *Leptospira* [Treponema] - Too thin to be seen with light microscopy in specimens stained with Gram or Giemsa stain - Motile spirochetes can be seen with darkfield microscopy (image 1) - Staining with anti-treponemal antibodies labeled with fluorescent dyes (image 2) - Intracellular pathogen - Three periplasmic flagella at each end - Does not survive well outside of host and cannot be grown in cell-free cultures *in vitro*  **Treponema and human disease**  ssp. means subspecies **Virulence factors of *T. pallidum*** - Outer membrane proteins promote adherence - Hyaluronidase (enzymes) may facilitate perivascular infiltration breaks down **hyaluronic acid**, a substance found in the connective tissue more easily penetrate these tissues and reach the spaces around blood vessels. - Antiphagocytic coating of fibronectin Fibronectin is a protein that naturally exists in the human body. It acts as a shield, making the bacterium less recognizable to the immune system. - Tissue destruction and lesions are primarily result of host's immune response while *T. pallidum* initiates the infection, most of the visible damage is caused by the body's attempt to fight off the bacterium **T. pallidum subsp. pallidum: causes Syphilis** - Transmitted from direct sexual contact or from mother to fetus - Not highly contagious (\~30% chance of acquiring disease after single exposure to infected partner) but transmission rate dependent upon stage of disease - Long incubation period during which time the host is non-infectious **Syphilis** - Tissue destruction and lesions are primarily a consequence of patient's immune response - Syphilis is a disease of blood vessels and of the perivascular areas - In spite of the host immune response the organisms are capable of persisting for decades - Infection is neither fully controlled nor erradicated - In early stages, there is an inhibition of cell-mediated immunity - Inhibition of CMI (cell-mediated immunity) in late stages of disease, hence late lesions tend to be localized The shift from widespread immune suppression in the early stages to localized immune activity in the late stages explains why late-stage syphilis symptoms tend to be more confined to specific tissues or organs **Primary Syphilis** - Primary disease process involves invasion of mucus membranes, rapid multiplication and wide dissemination through perivascular lymphatic and systemic circulation. Occurs prior to development of the primary lesion. - Usually 3-4 weeks after initial contact the host mounts an inflammatory response at the site of inoculation resulting in the hallmark syphilitic lesion, called the chancre = painless) - Chancre changes from hard to ulcerative with profuse shedding of spirochetes - Swelling of capillary walls and regional lymph nodes - Lesion heals spontaneously by fibrotic walling-off within two months, leading to false sense of relief **Secondary Syphilis** - Secondary disease 2-10 weeks after primary lesion - Widely disseminated mucocutaneous rash - Secondary lesions of the skin and mucus membranes are highly contagious - Generalized immunological response **Latent stage syphilis** - Following secondary disease, host enters latent period - First 4 years = early latent - Subsequent period = late latent - About 40% of late latent patients progress to late tertiary syphilitic disease **Tertiary syphilis (40% of late latent)** - Tertiary syphilis characterized by localized granulomatous dermal lesions (gummas) in which few organisms are present - Granulomas reflect containment by the immunologic reaction of the host to chronic infection - Late neurosyphilis develops usually more than 5 years after initial infection - Central nervous system and spinal cord involvement - Dementia, seizures, wasting, etc. - Cardiovascular involvement appears 10-40 years after initial infection with resulting myocardial insufficiency and death **Famous disease...** - The philosopher Friedrich Nietzsche, the musician Schubert, artists such as Goya or Van Gogh; Peter I and Catherine of Russia, Al Capone o Mussolini. **Congenital syphilis** - Congenital syphilis results from transplacental infection - *T. pallidum* septicemia (bacterial contamination) in the developing fetus and widespread dissemination - Abortion, neonatal mortality, and late mental or physical problems resulting from scars from the active disease - Penicillin remains drug of choice - WHO monitors treatment recommendations - 7-10 days continuously for early stage - At least 21 days continuously beyond the early stage - Prevention with barrier methods condoms - Prophylactic treatment of contacts identified through epidemiological tracing. When someone is diagnosed with syphilis, health authorities often try to trace individuals who may have been in close contact with the infected person, Once these contacts are identified, they are offered prophylactic treatment **Treponema pallidum subsp. Endemicum** - Causes Bejel (endemic syphilis) Not transmitted sexually - Initial lesions: oral lesions - Secondary lesions: oral papules and mucosal patches - Late lesions: gummas (granulomas) of skin, bones and nasopharynx - Transmitted person-to-person by contaminated eating utensils - Primitive tropical/subtropical areas (Africa, Asia and Australia) Endemic! **Treponema pallidum subsp. Pertenue**  - Yaws: granulomatous disease - Early: skin lesions - Late: destructive lesions of skin, lymph nodes and bones. Painless nodules widely distributed over body with abundant contagious spirochetes. - Transmitted by direct contact with lesions containing abundant spirochetes - Primitive tropical areas (South America, Central Africa, Southeast Asia) **Treponema carateum** - Pinta: primarily restricted to skin - 1-3 week incubation period - Initial lesions: small pruritic papules - Secondary: enlarged plaques persist for months to years - Late: disseminated, recurrent hypopigmentation or depigmentation of skin lesions; scarring and disfigurement - Transmitted by direct contact with skin lesions - Primitive tropical areas (Mexico, Central and South America) [Borrelia]  **Borrelia spp.** - Gram-negative spirochetes - Giemsa stain of blood, phase contrast microscopy - Antigenic shift and immune reactions are the responsible for the disease **Borrelia and human disease** **Relapsing fever** - Associated with poverty, crowding, and warfare - Arthropod vectors - Louse-borne borreliosis = Epidemic Relapsing Fever - Transmitted person-to-person by human body lice (vectors) from infected human reservoir - Infect host only when louse is injured, e.g., during scratching - Lice leave host that develops a fever and seek normal temperature host - Tick-borne borreliosis = Endemic Relapsing Fever - Sporadic cases - Transmitted by soft body ticks (vectors) from small mammal reservoir - Ticks can multiply and infect new human hosts **Pathogenesis of relapsing fever** - Acute infection with 2-14 day incubation period - Followed by recurring febrile episodes - Constant spirochaetemia that worsens during febrile stages Just before a fever episode, *Borrelia* multiply rapidly in the bloodstream, leading to a significant increase in their number **Epidemiology of Lyme borreliosis** - Lyme disease was recognized as a syndrome in 1975 with outbreak in Lyme, Connecticut - Associated to *B. burgdorferi* - Transmitted by hard body tick (Ixodes spp.) vectors - White-footed deer mice and other rodents, deer, domesticated pets and hard-shelled ticks are most common reservoirs  **Lyme disease** - Characterized by three stages: - Initially a unique skin lesion (erythema migrans, or bullseye rash) with general malaise. EM not seen in all infected hosts. Lesions periodically reoccur - Subsequent stage seen in 5-15% of patients with neurological or cardiac involvement - Third stage involves migrating episodes of non-destructive, but painful arthritis (disorder that affect joints) **Erythema migrans of Lyme borreliosis: bullseye rash (foto)** **Treatment** - Relapsing fever: tetracycline or erithromycine - Lyme disease: amoxicillin, tetracycline or cefuroxime [Leptospira] **Leptospira interrogans** - Gram negative spirochete - Characteristic hooked ends, like a question mark, interrogans) - Two periplasmic flagella - Tissue destruction and lesions are primarily result of host's immune response **Virulence factors** - Able to directly invade and replicate in tissues, inducing inflammatory response **Epidemiology of leptospirosis** - Mainly a zoonotic disease - Transmitted to humans from a variety of wild and domesticated animal hosts (rats, dogs, farm and wild animals) - Transmitted through breaks in the skin or [intact mucus membranes] - Indirect contact (soil, water, feed) suolo, acqua o mangime by infected urine from an animal with leptospiruria - Occupational disease of animal handling ex: vet, farmer, abattoir workers,... **Clinical disease: Leptospirosis** 1. Mild virus-like syndrome 2. Anicteric leptospirosis: systemic with aseptic meningitis inflammation of the meninges without bacterial infection in cerebrospinal fluid  3. Icteric leptospirosis or Weil´s disease: overwhelming disease with vascular collapse, thrombocytopenia (low platelet count, leading to bleeding), hemorrhage, hepatic and renal dysfunction can lead to multi olgan failure NOTE: Icteric refers to jaundice (yellowing of skin and mucus membranes by deposition of bile) and liver involvement **Pathogenesis of Icteric Leptospirosis** - Direct invasion and replication in tissues - Characterized by an acute febrile jaundice and glomerulonephritis inflammation of the **glomeruli**, the tiny filtering units in the kidneys - Incubation period usually 10-12 days with flu-like illness usually progressing through two clinical stages: - Leptospiremia develops rapidly after infection (usually lasts about 7 days) without local lesion - Infects the kidneys and organisms are shed in the urine (leptospiruria) with renal failure and death not uncommon - Hepatic injury and meningeal irritation is common **Treatment** - penicillin or doxycycline - Control of reservoirs, vaccination of animals [Micoplasmas] **Mycoplasmataceae** - Smallest (0.1-0.3 μm) bacteria - Grow slowly, need sterols and glucose as a source of energy - Ureaplasma spp. requires also urea - Facultative anaerobes - Except M. pneumoniae - strict aerobe - [Lack a cell wall] (for this no antibiotic that inhibit cell wall production ) - Resistant to penicillin, cephalosporins, vancomycin, but sensitive to tetracycline, erythromycin (inhibitors of protein synthesis) - Small, fried-egg-like colonies (except M. pneumoniae)  **Mycoplasmataceae and human disease** - Genus: Mycoplasma - Species: M. pneumoniae - Species: M. hominis - Species: M. genitalium - Genus: Ureaplasma - Species: U. urealyticum [M. pneumonia] ***M. pneumoniae* virulence factors** - Adherence - Mediated by P1 pili. Allows infection and colonization of mucous membrane (nose, throat, trachea, LRT). Adheres to sialated glycoprotein receptor at the base of cilia by means of P1 antigen - Movement of cilia ceases - Clearance mechanism stops resulting in cough - The bacteria acts like a superantigen, activates inflammatory cells and stimulates cytokine production **Clinical diseases by *M. pneumoniae*** - Mostly asymptomatic carriage - Acute pharyngitis: low-grade fever, malaise, headache, dry and nonproductive cough, persist for \> 2 weeks - Tracheobronchitis with lymphocyte and plasma cell infiltration - Atypical (walking) pneumonia - Secondary complications: hemolytic anemia, arthritis, myocarditis, pericarditis, neurologic abnormalities (such as meningoencephalitis) **Atypical (walking) pneumonia** - Chronic in both onset and recovery - Flu-like symptoms - generalized aches, discomfort, headache, chills, low-grade fever - Persistent non-productive cough A dry cough that doesn't produce mucus or sputum **(Typical pneumonia - bacterial pneumonia)** - Abrupt, rigorous onset - Productive cough, purulent sputum - High fever, chest pain, stiffness in the neck **Treatment and Prevention *M. pneumoniae*** - Treatment - Tetracycline or erythromycin or newer fluoroquinolones - Can't use cell wall synthesis inhibitors because they don't have cell wall - Prevention - Avoid close contact - No vaccine [Other Mycoplasmataceae ]  **Treatment** - *M. genitalium*: erythromycin, tetracycline - *Ureaplasma*: use erythromycin, resistant to tetracycline - *M. hominis*: resistant to erythromycin and tetracycline, use clindamycin - Avoidance of non-protected sex - No vaccine available