Mycobacteria, Spirochetes, and Other Bacteria PDF

MYCOBACTERIA, SPIROCHETES AND OTHER BACTERIA Deniz Sertel, PhD Spirochetes ◦ Thin, tightly coiled, helically shaped Gram negative bacteria ◦ Moves in a corkscrew fashion through its environment ◦ Due to rotation of axial filaments ◦ Enables pathogenic spirochetes to burrow through hosts' tiss...

MYCOBACTERIA, SPIROCHETES AND OTHER BACTERIA Deniz Sertel, PhD Spirochetes ◦ Thin, tightly coiled, helically shaped Gram negative bacteria ◦ Moves in a corkscrew fashion through its environment ◦ Due to rotation of axial filaments ◦ Enables pathogenic spirochetes to burrow through hosts' tissues ◦ Can not be seen under bright field light microscope, can be visualized with dark field or fluorescent microscope ◦ Three genera cause human disease: ◦ Treponema, Borrelia, and Leptospira  Spirochetes under fluorescent microscope 23.11.2023 Treponema ◦ Treponema pallidum pallidum ◦ Pathogen of humans only ◦ Causative agent of syphilis ◦ Transmission is almost solely via sexual contact ◦ Other means of transmission: blood, transplansental ◦ Endemic among sex workers, men who have sex with men, and users of illegal drugs ◦ Disease ◦ Untreated syphilis has four phases: ◦ Primary, secondary, latent, and tertiary ◦ Congenital syphilis ◦ An infected mother can transmit Treponema to her fetus via transplancental route ◦ Can result in fetal death or mental retardation and malformation Treponema pallidum pallidum.  The lesions of syphilis. 23.11.2023 Treponema pallidum: Diagnosis, Treatment, and Prevention ◦ Diagnosis ◦ Antibody tests against bacterial antigens ◦ Non-treponemal (VDRL, RPR), treponemal (FTA-ABS, TP-PA,EIA) ◦ Treatment ◦ Penicillin is the drug of choice ◦ Prevention ◦ Abstinence and safe sex Treponema ◦ Nonvenereal Treponemal Diseases ◦ Primarily seen in impoverished children in unsanitary conditions ◦ T. pallidum endemicum ◦ Bejel ◦ T. pallidum pertenue ◦ Yaws ◦ T. carateum ◦ Pinta ◦ Cause skin lesions ◦ Penicillin used to treat these diseases ◦ Prevent by limiting contact with skin lesions  Yaws. 23.11.2023 Borrelia Prevention: control and avoidance of vectors, personal Cause two diseases in humans: hygiene for louse borne disease ◦ Lyme disease ◦ Relapsing fever ◦ Borrelia burgdorferi is the causative ◦ Louse-borne relapsing fever agent ◦ Borrelia recurrentis is the causative ◦ Lacks iron-containing enzymes and agent proteins ◦ Transmitted to humans by the human ◦ Bacteria are transmitted to humans body louse via a tick bite ◦ Tick-borne relapsing fever ◦ Hard ticks of the genus Ixodes are the ◦ Several Borrelia species can cause this vectors disease ◦ Expanding red "bull's-eye" rash occurs at ◦ Transmitted to humans by soft ticks infection site ◦ Characterized by recurring episodes of septicemia and fever ◦ Due to body's repeated efforts to remove the spirochetes Borrelia burgdorferi. Borrelia Red blood cell Figure 21.12 The life cycle of the deer tick Ixodes and its role as the vector of Lyme disease. Uninfected, 6-legged tick larvae hatchSpring from egg, crawl up vegetation, and (Year 1) wait to jump on passing animal. Larvae Spring (Year 2) Tick larvae become Infected nymphs infected with Borrelia feed on animals or when they feed on humans, introducing small mammals or birds. Borrelia (year 2). After feeding for 3–4 days, they drop off. Larvae develop Female ticks lay into 8-legged uninfected eggs nymphs that Summer in fall (year 2). remain infected. Nymph Nymphs develop into adult ticks over the summer Adult ticks feed (year 2). Borrelia Winter on deer or other multiplies in animals and mate infected larvae. in fall (year 2). Fall  Second Third antibody antibody response response Second Third First First antigenic antigenic antigenic antibody challenge challenge challenge response 41 The time course of recurring Body temperature (°C) episodes of 40 fever in relapsing fevers. 39 38 37 8 10 12 14 16 18 20 22 24 26 Days following infection Leptospira ◦ Leptospira interrogans ◦ Motile, obligately aerobic bacteria ◦ Found in numerous wild and domestic animals (esp rodents) ◦ Leptospirosis ◦ Leptospira enters through the skin or mucous membranes (exposure to water contaminated with urine from an infected animal or handling of tissues from an infected animal) ◦ Travels via the bloodstream throughout the body ◦ Can cause hemorrhaging and liver and kidney dysfunction ◦ Eradication impractical due to the various animal reservoirs ◦ Vaccine available for livestock and pets Leptospira interrogans. Mycobacterium ◦ Thin straight or slightly curved rods ◦ Aerobe ◦ Have unique cell wall ◦ Cell wall contains a lipid called mycolic acid ◦ 60% is composed of lipids (long chain mycolic acids, free lipids, glycolipids, waxes …) ◦ Do not stain with Gram staining method ◦ Acid fast ◦ Consequences of the high lipid content: Acid-fastness; slow growth; resistance to detergents, common antibiotics, descication and host immune response Acid fast bacteria  Clinical Importance Mycobacteria M. tuberculosis complex TUBERCULOSIS Pulmonary dis. Non-Tuberculosis Mycobacteria Generalized dis. Cutaneous dis. M. leprae LEPROSY Mycobacterium tuberculosis ◦ Humans are the only natural reservoir ◦ Epidemiology: ◦ Most common cause of TB in humans ◦ ¼ of the world population is infected ◦ Transmission: respiratory droplets (human-human) ◦ Virulence: M. tuberculosis lacks the classical virulence factors such as capsule, flagella, toxins ◦ Pathogenesis: facultative intracellular pathogen (bacteria can multiply in macrophages), host immune reponse ◦ Disease: TUBERCULOSIS (TB) ◦ Latent TB, Active TB (pulmonary TB/extrapulmonary TB) ◦ Prevention and control: BCG vaccine, detection and treatment of TB patients 23.11.2023  Tuberculosis ◦ Infection characterized by granulamatosis inflammation (tubercule) ◦ Primarily affects the lungs but can involve any organ/tissue ◦ Primary TB: inital infection, doesn’t progress to disease (active TB) in most cases ◦ Post-primary/secondary TB: Dormant bacilli reactivate and active TB develops ◦ Active TB: TB bacilli multiply and the individual show signs and symptoms of the disease ◦ Latent TB: Bacilli are dormant, symptoms and signs are not seen ◦ TST and IFN-g release assay (+) ◦ Some patients’ CXR may show evidince of primary infection Mycobacterium leprae ◦ Humans are the reservoir ◦ Armadillos are the only known host other than humans ◦ Bacteria do not grow in cell-free culture ◦ Has low virulence ◦ Transmission: direct contact (with lesions or nasal secretions) and inhalation of respiratory droplets. Require long time exposure. ◦ Disease: Leprosy 23.11.2023  Leprosy ◦ Tuberculoid leprosy ◦ Nonprogressive form of the disease ◦ Due to a strong cell-mediated immune response ◦ Infectivity low ◦ Lepromatus leprosy ◦ More virulent form of the disease ◦ Due to a weak cell-mediated immune response ◦ Infectivity high ◦ Cases are becoming relatively rare ◦ Diagnosis: ◦ Based on signs and symptoms of disease ◦ AFB can be detected in specimens of patients with lepramatus leprosy Lepromatous leprosy can result in severe deformities. Non-Tuberculosis Mycobacteria ◦ Widespread in nature ◦ Human to human spread is unusual ◦ Transmission: direct contact, inhalation, ingestion ◦ Most of them have low virulence ◦ Most of them are resistant to anti-tbc drugs ◦ Can cause serious disease in immunosuppressed ◦ Mycobacterium avium-intracellulare is an important pathogen for AIDS patients ◦ Infections result from ingestion of contaminated food or water ◦ Affects almost every organ 23.11.2023 Chlamydias ◦ Obligate intracellular pathogens ◦ Once considered to be viruses ◦ Have unique cell walls ◦ Have two membranes without any peptidoglycan between them ◦ Grow and multiply only within the vesicles of host cells ◦ Have a unique developmental cycle involving two forms ◦ Elementary bodies (EBs) and reticulate bodies (RBs) ◦ Both forms can occur within the phagosome of a host cell  Elementary body (EB) attaches to receptor on host cell (0 hour). EB triggers its EBs are released own endocytosis from host cell by host cell. (40 hours). Vesicle Reticulate body (RB) Elementary body (EB) Inclusion body Most RBs convert back into EBs (21 hours). EB inside endocytic vesicle. EB converts into reticulate body (RB) within vesicle (10 hours). RB divides rapidly, resulting in multiple RBs. The vesicle is Inclusion now called an body inclusion body. Chlamydia trachomatis ◦ Has a limited host range: Humans are the primary host ◦ One strain infects mice; all others infect humans ◦ Enters the body through abrasions and lacerations ◦ Infects the conjunctiva and various mucous membranes ◦ Clinical manifestations due to cell destruction and inflammation Chlamydia trachomatis: diseases ◦ Sexually transmitted diseases ◦ Asymptomatic infection is common, esp in women ◦ Reinfection may cause pelvic inflammatory disease ◦ Most common cause of infection related sterility ◦ Lymphogranuloma venereum ◦ Initial genital lesion is followed by formation of buboes ◦ Buboes may enlarge and rupture producing draining sores ◦ Nongonococcal urethritis, Proctitis  An advanced case of lymphogranuloma venereum in a man. 23.11.2023 Chlamydia trachomatis: diseases ◦ Ocular diseases ◦ Transmitted via direct contact with infected secretions or indirect contact with contaminated objects, mechanichal vector ◦ Trachoma ◦ Endemic in Middle East, Africa and Asia, rare in developed countries ◦ leading cause of preventable blindness ◦ Scarring of the conjunctiva causes the eyelashes to turn ◦ Causes corneal abrasions that lead to blindness ◦ Adult inclusion conjunctivitis ◦ Generally seen in sexually active adolescents/adults with genital infection ◦ Can also be transmitted via autoinoculation 23.11.2023 The underside of an eyelid afflicted with trachoma. Chlamydia trachomatis: diseases ◦ Infections of the newborn ◦ Transmitted from mother to infant. Acquired during passage of the infant through an infected birth canal. ◦ Neonatal conjunctivitis ◦ Infant pneumoniae 23.11.2023 Chlamydophila pneumoniae ◦ Primary host is humans ◦ Causes bronchitis, pneumonia, and sinusitis ◦ Transmitted from person to person via respiratory droplets ◦ Most infections only produce malaise and a chronic cough ◦ Can resemble primary atypical pneumonia caused by Mycoplasma pneumoniae Chlamydophila psittaci ◦ Host: Primarily animals (birds) , occasionally infects humans ◦ The organism is present in the blood, tissues, feces, and feathers of infected birds that may appear either ill or healthy. ◦ Disease: Ornithosis / Psittacosis (parrot fever) ◦ Usually causes flulike symptoms ◦ Rarely nonrespiratory conditions are observed ◦ Individuals who handle animals are at greatest risk of infection ◦ Transmitted via inhalation of aerosols or contact with infected material or a pet bird ◦ Diagnosis difficult, since symptoms similar to other respiratory infections ◦ Prevention involves proper handling of birds Coxiella burnetii ◦ Extremely small, aerobic bacteria ◦ Obligate intracellular parasite ◦ Infective body enables survival in harsh environment ◦ Various animals (mammals, birds, turtles, and arthropods) are reservoirs but human disease is mostly associated with farm animals and pets ◦ Transmitted mainly by inhalation of the infective bodies Rickettsias ◦ Extremely small ◦ Appear almost wall-less due to small amount of peptidoglycan present ◦ Obligate intracellular parasites ◦ Transmitted via arthropods ◦ Susceptible to environmental conditions ◦ Four genera cause disease in humans: ◦ Rickettsia, Orientia, Ehrlichia, and Anaplasma Rickettsia spp ◦ Nonmotile, aerobic bacteria ◦ Transmitted via arthropod vectors ◦ Have an affinity for endothelial cells ◦ Bacteria live in the cytosol of host cell ◦ Disease is characterized with fever, headache, rash ◦ Typhus group ◦ Spotted fever group ◦ Typhus: ◦ R. prowazekii (epidemic typhus, reservoir: human, vector: lice) ◦ R. typhi (endemic typhus, reservoir : Mouse, rat, vector : flea) ◦ Spotted fever (SF): ◦ R. akari (rickettsial pox, vector: mite) ◦ R. conori (mediterenean SF, vector: tick) ◦ R. rickettsii (Rocky mountain SF, vector: tick) 23.11.2023 DISEASE IN DEPTH ROCKY MOUNTAIN SPOTTED FEVER Rickettsia INSIDE BLOOD VESSEL INSIDE BLOOD VESSEL R. rickettsi escaping into cytosol PATHOGENESIS Endothelial cells lining small blood vessel Endosome Rickettsias divide every 8–12 hours in the host cell's cytosol. Daughter Engorged rickettsias escape from long cytoplasmic Dermacentor extensions of the host cell and infect R. rickettsi triggers other endothelial cells. endocytosis by cells lining blood vessels (endothelium); then it lyses the endosome’s membrane, escaping into the cytosol. Infected tick introduces R. rickettsii in its saliva. This occurs only after the tick has fed for at least six hours. Active bacteria are released into the mammalian host’s circulatory system.  R. rickettsii secretes no toxins, and disease is not the product of immune response. Apparently, damage to the endothelial cells leads to leakage of blood into the tissues, which results in low blood pressure and insufficient nutrient and oxygen delivery to the body’s organs. Blood leaks into tissue R. rickettsii escaping an endothelial cell Subcutaneous hemorrhages (petechiae) of RMSF patient Boutonneuse/MSF Mycoplasmas ◦ Smallest free-living microbes ◦ Lack cell walls, have sterols in their cytoplasmic membranes ◦ Require various growth factors from a host or supplied in laboratory media ◦ Can colonize the mucous membranes of the respiratory and urinary tracts of humans Colonies of Mycoplasma. «Fried egg» appereance Mycoplasma pneumoniae ◦ Attaches to epithelial cells lining the human respiratory tract ◦ Removal of mucus impaired, allowing bacteria to colonize ◦ Transmission: respiratory droplets (human-human) ◦ Clinical significance: primary atypical pneumonia ◦ Early symptoms not typical of other types of pneumonia ◦ Not usually severe enough to require hospitalization ◦ Sometimes called walking pneumonia ◦ Common in children 5 to 15 years old Figure 19.19 Mycoplasma pneumoniae. Other Mycoplasmas ◦ M. hominis, M. genitalium, and Ureaplasma urealyticum ◦ Associated with human diseases ◦ Often colonize the urinary and genital tracts of humans ◦ M. genitalium and U. urealyticum ◦ Cause nongonococcal urethritis ◦ M. hominis ◦ Can cause pelvic inflammatory disease (PID) in women ◦ Abstinence and safe sex can help prevent the spread of these organisms