eukaryotic microbial diseases

8/10/2019 Eukaryotic Microbial Diseases

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Eukaryotic Microbial Diseases


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Eukaryotic Diseases Present Extra Challenges

Because bacteria and other prokaryotes use very different proteins

and mechanisms for maintaining their cells vitality than humans do, itis relatively easy to design drugs that will interact with the bacterialtargets, but will not interact with the analogous proteins and othermolecules in humans

The proteins and mechanisms used by eukaryotic pathogens tomaintain their vitality are more similar to those we use to maintain ourvitalitythe potential for cross-reactivity and side effects is greater


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Protozoans Are Our Most

Common Eukaryotic Pathogens

Most fungi that inhabit the human body are commensals, but can beopportunistic, and take advantage of factors such as a shift in the microbialenvironment, pH, or suppressed immune system function

Fungi often cause skin infectionsathletes foot, ringworm, jock itch


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CandidaAn Opportunistic

Fungal Pathogen

Thrushinfected patches inthe oral mucous membranes

Candida infection in thethumbnail


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Transmission Can Be By Direct Contact

Or Through Vectors

Ex. growth of the Ophiostoma novo-ulmi fungus that causes Dutchelm disease clogs up the water-carrying tubes in the trees xylem,which kills the tree

If two elms stand close enough together for their roots to touch, thefungus can move from one trees roots to the other

Burrowing beetles burrow into the dead tree and lay their eggs; whenthe young hatch out, they fly out of the tree covered in fungal spores,

which are reproductive cells that can survive in harsh environmentsfor a time

The beetles carry the spores, then transmit them to other trees whenthey bore into them


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Or Through Vectors

Some have simple life cyclesthey complete their life cycle within asingle species

Ex. the diarrhea-causing protozoan Giarida lambliaForms cysts,protected by a special cell wall, that are ingested in food or water

Once ingested, the excystation produces trophozoites, which replicatein the small intestine

The trophozoites form cysts in the large intestine, to be excreted inthe feces


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Or Through Vectors

Some have complex life cyclesthey undergo different phases oftheir life cycle in different hosts

Ex. the protozoan that produces malariaReplicates sexually in themosquito (the definitive host)

Transmitted to a human (the intermediate host) through bites, inwhich it replicates asexually and differentiates


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Plasmod ium Falc iparumHas A

Complex Life Cycle


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Pathogens Need To Attach

Some use specialstructures, ex. the diarrhea-

inducing Giardia lambliahas a ventral disk that ituses to adhere to the cellsthat line the small intestine


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Pathogens Need To Attach

The malaria-inducing protozoan Plasmodium falciparumforms merozoitesin the human liver; they use merozoite surface proteins to attach to and

penetrate human red blood cells


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Pathogens Take Advantage Of A

Compromised Immune System

Opportunistic pathogens only invade when the hosts immune system has

been compromised, ex.When people are given immunosuppressive drugs for organ transplants

People who have autoimmune diseases

When antibiotics kill beneficial bacteria

As a side effect of other infections, such as HIV reducing the effectivenessof CD4+ helper T cells


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Pathogens Take Advantage Of A

Compromised Immune System

Ex. Patients with HIV infections often are also infected by the protozoanToxoplasma gondii, which is often acquired from cats

Pneumocystis jirovecii is a fungus that inhabits the human lung; manypeople have antibodies against it in their bloodstreampeople with HIVoften get infected by it

Ex. The fungus Candida albicansis a commensal fungusit inhabits thehuman mouth, throat, rectum and vaginaOne of the side effects ofantibiotics can be thrush (in the mouth and throat), finger/toe nail infectionsor vaginal yeast infections


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Pathogens Need To Evade

The Hosts Immune System

Some pathogens constantly change their cell surface molecules to evadehost detectionthis can even allow the pathogen to reinfect someone who

has already acquired an immunity to that pathogen

Ex. Trypanosoma bruceii cells are coated with a single glycoprotein, but itchanges (referred to as a variable surface glycoprotein)

The T. bruceii genome has thousands of genes that encode the surfaceglycoproteinit turns one on at a time


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Pathogens Need To Evade

The Hosts Immune System

The sleeping sickness is cyclical

The hosts immune system kills a lot of the invaders, and the person getsbetter

However, by the time the first immune response has had time to mount aneffective defense, the remaining pathogens are expressing a different cellsurface glycoprotein, and the hosts immune system has to recognize them

and mount a new immune response to them (any memory cells it has dontrecognize the new glycoprotein)

The pathogens with the new surface antigen thrive, and the person getssick again


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The Pathogen Needs To Nourish Itself

Many fungi secrete enzymes that break down host tissues and providenutrients for the fungus

Ex. Plant fungi (phytopathogenic fungi) secrete enzymes that degrade themajor components of cell walls:

cellulases (digest cellulose)

pectinases (digest pectin)

proteases (digest proteins)xylanase (digests hemicellulose)


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Other fungi physically force their way into the host cell

Ex. the fungus Magnaporthe grisea, which causes rice blastretains a lot ofwater, producing a lot of internal pressure

Some of the hyphal cells are called apressoriathey grow structures calledpenetration pegs which, backed by the high intracellular pressure, penetratethe host cells


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Apressoria And Penetration Pegs

Hypha


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Pathogens often deprive the host of a critical nutrient

Ex. The malaria-causing protozoan Plasmodium falciparumcannotsynthesize purine bases (adenine and guanine); it penetrates the hosts redblood cells, lives inside them and takes purines from the host cellscytoplasm

This would prevent a cell from synthesizing nucleic acids, ATP, GTP and

other important molecules

They also consume the hosts hemoglobin, releasing heme, which iscytotoxic


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Eukaryotic Microbes Produce A

Variety Of Toxins

Some produce HC-toxin, which inhibits histone deacetylases (HDACs)

HDACs remove acetyl groups from histones, thereby turning genes off

HC-toxin leaves the host unable to turn certain genes off


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Variety Of Toxins

TheAmanita mushrooms produce alpha-amantin, which binds to RNA

polymerase II, the enzyme that generates most protein-coding mRNAs

TheAmanitas RNA polymerase II is resistant to the toxin

This is an intoxication, not an infection


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Variety Of Toxins

Some marine dinoflagelates (algae with two flagellae), cyanobacteria

and algae produce toxins that create what is known as harmful algaeblooms (slang term = red tide), which kills fish, birds and mammalsinduces paralysis in humans

These toxins (ex. saxitoxin) block sodium channels, preventing nervesfrom firing, resulting in flaccid paralysis

These are thought to defend the microbes against predatorsthemicrobes increase toxin release when they sense the presence of apredator


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Evolution Of Eukaryal Pathogens

And Their Hosts

Some acquire toxin-producing genes through lateral gene transfer

The host may evolve as wellex. fruit flies that breed inAmanitamushrooms have evolved resistance to alpha-amanitin

They get covered with it, which protects them from parasitic worms


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Good Review Questions From This Unit

Chapter 23 Application Questions1-4, 7, 8

eukaryotic microbial diseases

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