Urinary Tract Infection Microbiology

What are some possible viruses that can cause renal dz?

-Adenovirus type 11 -Enteroviruses -Coxsackieviruses -Polyomaviruses (from transplant) -Herpesviruses (from transplant)

How does Cystitis present?

-Dysuria -Frequency increase in urination and urgency -Suprapubic pain

How does Severe pyelonephritis present?

-High fever -Rigors -Nausea -Vomiting -Flank pain

TEST: List some of the most common risk factors for UTIs.

-Incomplete emptying and flushing of the bladder due to neuro deficit or prostatic hypertrophy -Obstruction -Vesicoureteral reflex -Catheters -Pregnancy -Presence of Gal-Gal Receptor -Sexual activity

What are some of the most common symptoms of prostatitis?

-LOWER BACK pain -Pain in the PERIRECTAL or TESTICULAR area

How does Mild Pyelonephritis present?

-Low grade fever -W/ or w/o lower back or CVA pain

What are some other species besides S.Aureus and Candida Albicans that can cause hematogenous (descending) UTIs?

-Mycobacterium tuberculosis -Salmonella spp. -Brucella spp. -Enterococcus faecalis

What is Emphysematous pyelonephritis?

-Severe form of the dz that is associated w/ the production of gas in renal and perinephric tissues and occurs almost exclusively in diabetics

UTIs can be broadly categorized by their entry and source of infection. What are the 2 possible entry sites/source of infection?

1) Entry site = Urethra Path= ASCENDING Source of infection: Exogenous 2) Entry site = Kidney through blood vessel Path= DESCENDING Source of infection= Hematogenous

TEST: List 6 of the major host defenses against UTIs.

1) Urine flow 2) Anti-adherence factors (Tamm-Horsfall protein, THP) 3) Anti-microbial factors (NO, cathelicidin, defnesins) 4) Exfoliation of cells 5) Production of chemokines and cytokines 6) Neutrophils

Define uncomplicated UTIs

Acute cystitis or pyelonephritis in NONPREGNANT OUTPATIENT women w/o anatomic abnormalities or instrumentation of the urinary tract -Rarely progress to severe disease

Define complicated UTIs

Acute cystitis or pyelonephritis in the presence of functional/metabolic/anatomic conditions that INCREASE THE RISK OF Tx FAILURE or serious outcomes -Stones, obstruction, pregnancy, diabetes, neurogenic bladders, etc...

TEST: What virulence factor initiates exfoliation of affected uroepithelial cells, forming pores and exiting?

Alpha-hemolysin (HlyA)

RECALL: What are the 3 major streptococcus groups? List the MAJOR species in each subgroup?

Alpha-hemolytic -Strep. pneumoniae (optochin sensitive) -Strep. viridans (optochin resistant) Beta-hemolytic -Strep. pyogenes (group A, Bacitracin sens.) -Strep agalactae (group B, bacitracin resis.) Gamma-Hemolytic -Enterococcus (Group D)

TEST: When hematogenous UTIs do occur, the most likely BACTERIA is what species? What about the most likely YEAST species?

Bacteria: STAPH AUREUS Yeast: CANDIDA ALBICANS (producing deep systemic infection like endocarditis)

TEST: What virulence factor of UPEC provides resistance to antimicrobial agents and immune clearance?

CAPSULE -Extracellular: Protects from opsonization, phagocytosis, complement mediated killing -Intracellular: Forms biofilms needed for proliferation and persistance

RECALL: What is a gram negative bacteria that ferments lactose?

E.Coli

When you think of UTIs, the first organism that should come to mind is what? Why?

E.Coli -This is by far the most abundant species among the ENDOGENOUS FLORA of the colon, which is the ultimate source of UTIs (both upper and lower tracts)

Facultative gram negative rods are also a member of the family of bacteria called what?

ENTEROBACTERIACEAE

Name this species: Facultative gram positive cocci that is nitrate reductase negative and catalase negative.

Enterococcus

RECAP: List the virulence factors responsible for UPEC: -Entrance (3) -Survival and reproduction (5) -Exit (1)

Entrance: -Type I Pili, P Pili, Type III secretion system Survival/reproduction: -SisA and SisB -Capsule -Shape change -Quiescent stage -Hemolysin and siderophores for Fe acquisition

TEST: What special stain is particularly selective for Gram-negative bacteria?

Eosin Methylene Blue (EMB)

TEST: What kind of species is more likely to cause ascending UTIs, and what are some examples?

FACULTATIVE GRAM NEGATIVE RODS: -E.coli -Proteus -Klebsiella -Enterobacter spp. -Serratia Pseudomonas (obligate aerobe)

Enterobacteriaceae are (obligate or facultative) gram (positive or negative) species that are oxidase (positive or negative) and nitrate reductase (positive or negative)?

FACULTATIVE gram NEGATIVE species that are oxidase NEGATIVE and nitrate reductase POSITIVE

T/F: A facultative anaerobic organism die in the presence of oxygen.

FALSE "Facultative" Implies the organism is capable of making ATP by aerobic respiration IF oxygen is present (but is capable of fermenting in the absence of it)

T/F: Descending UTIs are much more common than those of exogenous origin.

FALSE -Ascending UTIs are far more common (95%), which makes sense b/c it is much easier to colonize the SKIN and mucosal surfaces adjacent to the urethral meatus than it is to get a bloodstream infection

T/F: All oxidase negative species are anaerobic.

FALSE -Just means they don't have cytochrome c oxidase to oxidize test reagents. These species may or may not be anaerobic, as there are still other oxidases in the ETC that can be used for aerobic respiration.

What is the main feature that distinguishes cystitis and polynephritis?

FEVER -Fever more associated with pyelonephritis

RECALL: Coagulase is used to convert _____ to_____, and is used to distinguish between species of what?

FIBRINOGEN to FIBRIN Used to distinguish between types of STAPHYLOCOCCUS isolates

TEST: Ascending UTIs are primarily from what kind of bacterial species?

Facultative gram NEGATIVE RODS (like E.coli)

AGAIN: Nitrites in the urine can indicate the presence of what?

Gram-negative rods as they have NITRITE REDUCTASE

RECALL: What is the function of Tamm-Horsfall protein?

It adheres to type I Pili, BLOCKING the attachment of pathogens to this pili and promotes "washout" of the bacteria

UTIs are (more or less) common in men. Why?

LESS common b/c: -Longer urethral length -Less frequent colonization around urethra -Prostatic fluid contains antibacterial substances

Leukocyte esterase is an enzyme of _____.

NEUTROPHILS

What is Xanthogranulomatous pyelonephritis?

Occurs when chronic urinary obstruction (often staghorn calculi), together w/ chronic infection leads to suppurative destruction of renal tissue

TEST: What virulence factor allows UPEC to adhere and colonize uroepithelium? What are the 2 types of this virulence factor, and what do each type attach to?

PILI -Type 1 pilus = common pilus (FimH for Adhesin), attaches to mannose containing glycoprotein receptors (uroplakings) -P Pilus, PapG for Adhesin, attaches to Gal-Gal- receptor

TEST: This gram negative species causes ~44% of catheter associated UTIs in the US. What kind of virulence factors does this species contain?

PROTEUS (shape shifter) Mirabilis Virulence factors include: -Production of hemolysin -IgA Protease -Iron acquisition -Flagella -Fimbriae -Secretion of UREASE

AGAIN: Which species is particularly prone to developing infectious stones? What virulence factor aids in this?

PROTEUS MIRABILLIS -Virulence factor: UREASE

UPEC species can convert into a _____ state that allows for it to cause ______infections.

QUIESCENT state that allows for it to cause RECURRENT infections

What does the enzyme nitrate reductase do? When this is positive in bacteria, what does this represent?

Reduces nitrate to nitrite This just represents PRESENCE OF BACTERIA

TEST: Besides a capsule, UPEC also can change ____ to try and avoid phagocytosis.

SHAPE

What parasite is a known urogenital pathogen?

Schistosoma Haematobium

TEST: What two proteins act as virulence factors for UPEC that suppress the host inflammatory response? Whic one is particularly correlated w/ Pyelonephritis?

SisA and SisB SisA is particularly correlated w/ Pyelonephritis

Name the species: Gram positive cocci that is catalase positive, coagulase negative and novobiocin sensitive.

Staph. EPIDERMIDIS

Name this species: Gram (+) cocci that is catalase positive, coagulase negative, nitrate reductase negative and navobiocin resistant.

Staph. SAPROPHYTICUS

What factor/phenotype of Proteus Mirabilis facilitates ascent into the urinary tract?

Swarm cell differentiation, charcterized by the formation of very LONG FLAGELLAE

T/F: Hematogenous UTIs are secondary to a primary bacteremia or other infection into the blood.

TRUE

T/F: The incidence of UTIs is greater in older females than in older males.

TRUE

T/F: Male UTIs are a type of "Complicated" UTI

TRUE -Since being male and having a UTI increases the risk of more serious infections

T/F: All oxidase positive species are aerobic.

TRUE By definition, oxidase positive means the species has cytochrome c for the ETC

RECALL: What protein is responsible for forming urinary casts, and in what part of the nephron do they form?

Tamm-Horsfall mucoproteins Forms in the DISTAL CONVOLUTED TUBULE

How did uropathogenic E.Coli species come about?

Through transfer of PATHOGENICITY ISLANDS

TEST: What virulence factor allows UPEC to gain entry into cells?

Type III secretion system (not present in all UPEC though)

The most common type of E.coli that causes ascending UTIs is what type?

UPEC (Uropathogenic E. coli)

TEST: How do you Dx UTIs, and what is the main problem w/ this method?

URINE DIPSTICK and UA: Look at the urine for: -Bacteria -WBCs (pyuria) -Nitrites -Leukocyte esterase Problem: Contaminants (fecal and vaginal flora/WBC)

RECAP: List the species that are most commonly found in : -Uncomplicated lower tract UTIs -Uncomplicated upper tract UTIs

Uncomplicated lower tract: E.Coli and staph Saprophyticus, other enterobacteriaceae Uncomplicated upper tract: E.coli (UPEC)

UTI's can be divided into infections confined in the lower tract and lower tract. What are these known as?

Upper Tract: Pyelonephritis Lower Tract: Cystitis

Explain how Proteus Mirabilis uses its secretion of UREASE as a virulence factor.

Urease hydrolyzes urea to ammonia and carbon dioxide, and ammonia combines w/ hydrogen --> Ammonium This decreases the amount of Free H in the urine, ALKALINIZING the urine. This promotes the PRECIPITATION of phosphate, carbonate, and magnesium--> Formation of STRUVITE stones --> PERMANENT source of bacteria