IMMI Slides – Flashcards

Shape and Staining characteristics (Gram or acid-fast reactions)

rods lined up side by side like fence (corynebacterium diptheriae)

Mycoplasmas have no peptidoglycan

Mycobacteria

Mycolic acid in mycobacteria cell wall binds to basic fuchsin and cannot be washed out by treatment with acid alcohol.

LTA, lipoteichoic acid. LTA links the inner membrane to the peptidoglycan

B-1,4-glycosidic

N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)

They bind carboxypeptidases and inactivate them. The carboxypeptidases normally cleave the terminal D-alanine in order to allow crosslinking between the secondary alanine and DAP

They are linked by a series of glycines that attach to lysine. Gram+ have much more crosslinking.

It cleaves the b-1,4 linkages between NAG and NAM

Lipopolysaccharides compose the outer membrane of gram negative cells (along with phospholipid) and forms a tight hydrophobic barrier. It is released upon death and acts as an endotoxin, activating inflammatory mediators. It is heat-stable.

Stabilization of outer membrane to periplasm

In LPS (or endotoxin). It is a glucosamine disaccharide whose hydroxyl groups are esterified with FA. It is essential for cell viability. It is the source of toxicity which is mediated through induction of TNF-a

In between the inner membrane and the cell wall. It has solute binding proteins, hydrolytic enzymes, and detoxifying agents.

S layers are a patterned array of glycoprotein on the surface of bacteria. Helps glycocalx with protection, shape, and adhesion

Fibrous material that is generally polysaccharide. Helps glycocalyx in adhesion and protection against phagocytosis

Proteinaceous structures composed of pilins, found more often on gram negatives. Functions in adherence using an adhesin.

Internally - called axial fibrils/filaments

Spores are formed by Bacillus and Clostridium (gram positive rods) in response to nutrient depravation. 

Capsular polysaccharide for the most part although a few are made up of live or killed bacteria.

Gyrase (topo II) - relaxes DNA to introduce supercoils

topoisomerase I - relaxes supercoils

Fluoroquinilones (Ciprofloxacin)

Rifampin, which is bacteriacidal, (prevents DNA->RNA, ie rna synthesis)

its a beta lactam, interferes with peptidoglycan synth

A plasmid that encodes the information for their own transfer to other organisms. It is also known as a mobile plasmid and can mobilize nonmobile plasmids.

Lytic, which involves phage DNA replication, phage assembly, and cell lysis. Lysogenic simply involves DNA intergration and bacterial replication.

Insertion sequences are much smaller (1 kb) and only contain information for transposition. Transposons are much larger (5-20kb), carry additional genes, and are organized in two classes - one has insertion sequences on either side and the other doesn’t.

Cute and paste and replicative transposition.

Transformation involves the uptake of naked, extracellular DNA and transduction is the transfer of DNA via phage infection.

S. pneumoniae, H. influenzae, and N. gonorrhoeae are capable for natural transformation. (SpHiNg)

Competence factor is secreted and induces the expression of mostly cell surface proteins. This enables DNA to bind to the surface of the cell, and one 7-10kb strand enters and recombines.

Conjugation is most significantly used in the intestines where gram negative facultative rods (E. coli) and other Enterobacteriaceae transfer antibiotic resistance gene among themselves.

Virus particle with non-viral DNA - 1/1000 chance of being produced. It cannot replicate but introduces the foreign DNA. Transduction only occurs when this DNA is accepted and recombined into the chromosome.

Minimum inhibitory concentration - the smallest amount of antimicrobial that inhibits growth

Minimum lethal concentration - the smallest amount that kills 99.9% of a portion of bacterial sample in a given amount of time

The ratio of the dose which is toxic to the hose to the dose which is effective against infection.

It inhibits bacterial cell wall synthesis. Similar to penicillin, the beta-lactam ring mimics the peptide bond formed during the transpeptidation (cross-linking) step of bacterial cell wall synthesis and binds the enzyme responsible. This induces autolysis of the cell.

Vancomysin is only effective against gram positive bacteria. Vancomycin is bactericidal and recognizes L-D-D configuration, which occurs only in NAM. It blocks crosslinking and the bactoprenol attachment, inhibiting the catalytic addition of the disaccharide to the growing peptigoglycan chain. Inhibits cell wall synthesis.

Aminoglycosides are bacteriacidal (streptomycin, gentamycin, neomycin) and target the 30S subunit. They are useful against many gram-negative rods. They both block the formation of the initiation complex and cause the ribosome to misread the genetic code. No protein synthesis. Ototoxic

Tetracyclines inhibit a broad spectrum of bacteria (mycoplasmas, chlamydiae, rickettsiae). They bind to the 30S ribosome and make the binding of aminoacyl-tRNA unstable, interrupting elongation. No protein synthesis. Limitation in that they can also bind eurkaryotic ribosomes. 

Chlorampenicol targets the 50S subunit and blocks peptidyl transferase activity by blocking tRNA binding to the A site. It is bacteriacidal against SpHiNm.  No protein synthesis.

Clindamycin is a lincosamide and interacts with both the A and P sites, causing the ribsoome to disassemble. It is bacteriostatic.  No protein synthesis.

It binds to the beta subunit of RNA polymerase and blocks the initiation of transcription. No RNA synthesis. It is bacteriacidal.

They work by binding the A subunit of DNA gyrase, interfering with supercoiling required for DNA replication.

They block folic acid synthesis by competitively inhibiting PABA. It is bacteriostatic. Without folic acid, bacteria cannot grow

A combination of a sulfonamide and trimethoprim. Trimethoprim is a dihydrofolate reductase inhibitor. This prevents the conversation of DHF to THF and folic acid/de novo AA synthesis

Cycloserine, used to treat TB

Prevents linkage of NAM to NAG by binding bactoprenol, the lipid carrier, and preventing its dephosphorylation. Only used on gram positive infections due to toxicity.

It binds to the 50S subunit and creates malformed peptides

Intrinsic (vancomycin cant penetrate gram neg outer membrane)

Acquired (mutation allows resistance or new DNA with resistance proteins)

Multi-drug resistant pumps have evolved. Most are antiporters driven by proton motive force. There are also ABC transporters powered by ATP.

They have internal drug binding pockets (with glutamate) which are exposed in binding. This one transporter can bind  a range of cationic drugs (bind to a glutamate).

An efflux pump may only be active when an antibiotic binds its repressor. Also, conjugation increases a thousand fold when the drug is present. Plasmid mobility genes are turned on.

In other drugs, binding can change secondary structure, allowing for transcription of normal proteins.

First step in infection is attachment - it can competitively inhibit this. Flora can also help with antibacterial factors, metabolism, stim of immune system, cross reactive antibodies.

Loss of NF allows abnormal bacteria to proliferate

Corynebacterium spp

S epidermidis

S. aureus

Streptococci

- alpha hemolytic streptococci

(most dominant - tightly bound to squamous cells)

-gram neg anaerobic bacilli (lots), facultative cocci, etc

-Alpha streptococci

-Gram neg anerobic bacilli (lots) and cocci

-haemophilus spp (lots)

more yeast in stomach, high density, many organisms. This replaces the streptococci and lactobacillus (gram pos bacillus)

Enterococci

facultative Gram negative bacilli

anaerobic bacteria

- anaerobic gram negative bacilli - most abundant

-Anaerobe:facultative = 100:1

-E coli = high turnover

-lactobacilli maintain pH and are very important

-group B streptococcus = transient NF during reproductive time

Normally lung has no anaerobes but can cause issue if large number of bacteria from pharynx enter

Dental trauma can lead to alph strep

Bacteremia can lead to endocarditis, where extremely sticky alph strep stick to mucosa.

-pathogens can now attach, will find facultative gram neg bacilli

-treating a small number of pathogens can cause a larger problem in GI

-vagina can lose protective pH

-greater susceptibility to enteric pathogens

-C difficile constitutively produces toxin when antibiotics are produced, normally in low numbers

Nucleocapsid proteins which bind to the genome

Capsid proteins which surround the genome

Envelope which is made up of host lipids and surrounds the virus and work in attachment

Protect the genome, attach and enter permissive cells, and to initiate virus gene transcription and genome replication.

Naked Helical Capsid.

Naked Icosahedral 

Enveloped Helical 

Enveloped Icosahedral Capsid - the amount of glycosylated protein makes it look like a fried egg

Poxvirus

Virus uses receptors to get into the cell, namely cell membrane proteins, ECM proteins, and receptor mediated endocytosis.

Uses host RNA polymerase to make a +strand which can be used to make proteins

Normal dsDNA viruses use either host or viral DNA polymerase to copy. Hepadnavirus, however, makes RNA out of its DNA using host RNA polymerase, and then uses its own viral reverse transcriptase to generate a copy.

ssDNA uses host RNA polymerase to make protein and host DNA polymerase to copy - only package one strand.

Protein synth - just read off of +RNA

Genome rep - copy to neg strand and then make copies off of that using its own RNA pol

Protein synth - need to make complement using their own RNA-dependent RNA polymerase

Genome rep - copy to pos strand and then make copies off of that using its own RNA pol.

Protein synth - use their own RNA polymerase to make message (off of neg strand)

Genome rep - use message to make copies, using its own RNA pol

Genome rep and Protein synth - use its own reverse transcriptase (RNA dependent DNA polymerase) to create DNA, integrates this into host genome, and then uses the hosts DNA-dependent RNA pol II to make mRNA or a genome copy. This can be translated to protein.

one long polyprotein gets chopped up into peptides. Later, ATP dependent processes open up pores.

Doesn’t make one long message but several short messages.

Have additional steps of transcription to + strand and glycoprotein envelope maturation.

Things go in different phases - Nucleus (in and out), early intermediate and late transcription/translation

Same as naked icosahedral except need to Pick up gel layer 

the latency associated transcript (LAT) produces only one pre-mRNA, which makes a lariat -> no virus replication and daughter cells will be latently infected.

Subclinical infections, no apparent disease

Enter at portal, spread to local lymph notes, replicate at local lymph, spread to bloodstream = primary viremia, which hits the central focus. Secondary viremia takes the virus to the target organ, the infection of which makes the disease apparent.

It persists in the epithelium of cervix but is acute localized

Chronic, latent (waves of activation and replication but undetectable when gone), and slow (low levels, takes years, mostly asymptomatic).

Infectious virus is always detectable and is often shed. Latent infections can always be checked.

In addition to adenovirus and HIV, we have:

Rubella = togavirus (ss+RNA, icosahedral env)

HBV = hepadnavirus (dsDNA circular, icosahedral env)

Hep C = flavivirus (ss+RNA, icosahedral env)

human T cell = retrovirus

PS Measles SSPE (paramyxo) is slow

organelles, sterol in cell membrane, chitin in cell wall, spores, thermal dimorphism, requirement for organic carbon.

Zygomycota.

Basidiomycota, ascomycota, and deuteromycetes all have septate hyphae.

Zygomycota, Basidiomycota, Ascomycota.

Deuteromycetes is also known as mitosporic fungi.

Separate kingdom from Fungi and forms oomycota

Glucan and chitin (inner layer).

The cell wall is 90% carbohydrate and gives shape and plasticity. Glycoproteins mediate outer layer recognition of fungi.

-Adaptation to in vivo environment

-escape from host recognition

-persistence and dissemination

Primary pathogenic fungi and switch shape from hyphae to rounded yeast-like cell and the other way around, contributing to virulence. Multifactorial processes and biofilm formation are the other two main forms of virulence.

Colonization, which only leads to a superficial infection.  Fungi can get deep-seated infection with the use of immunomodulators and disseminated infection with antioxidants.

Need Th1 adaptive immunity (IFN-y) against fungus

Cutaneous, subcutaneous, systemic, and opportunistic (nonpathogenic until introduced to a specific environment)

disrupt membrane function

(Amphotericin B - binds to ergosterol - water insoluble). This is fungicidal.

Azoles - block ergosterol synthesis (water soluble) - fungostatic - fungus fight back using efflux pumps

Allylamines work similarly

Lanosterol C-14 demethylase is a crucial intermediate enzyme in fungal sterol biosynthesis pathway.  It is targeted by azole class of antifungals.

Echinocandins - target cell wall synthesis (water insoluble) - inhibit B-1,3-D-glucan synthase and disrupt cell wall - fungus fights back by changing the targeted gene conformation

(Flucytosine 5FC - inhibits DNA/RNA synthesis)

Dematiceous fungi can also come from implantation from soil and vegetation, which is the primary disease. Inhalation may affect debilitated patients.

Cadidiasis, Aspergillosis, Cryptococcosis

One of the most common nosocomial infections and predisposition develops in antibiotic therapy (kill surrounding bacteria), catheters, immunosupression, burns, drug use, surgery