Klebsiella

Gram stain of klebsiella

negative

motility of klebsiella

usually non-motile

where is klebsiella

all over due to niche specialization

Disease associated with Klebsiella granulomatis

genital ulcers transmitted as an STI

disease associated with K. huaxiensis

isolated from recalcitrant human UTIs;

disease associated with K. variicola

benign endosymbiont of plants that may aid in nitrogren fixation by promoting fine root hairs; some instances of causing URIs in humans; bovine mastitis

What is the reason behind K. aerogenes name

produces a lot of hydrogen

what is one of the few Klebsiella species that can be motile

Klebsiella aerogenes due to its peritrichous flagella

where is klebsiella typically found

gastrointestinal tract and can cause opportunistic nosocomial infections

Where is K. aerogenes particularly prevalent:

Europe, especially France

what types of infections does Klebsiella Aerogenes cause

gastrointestinal, respiratory, bloodstream, and urinary infections

What is the #2 disease causing klebsiella species in the US?

Klebsiella oxytoca

How is Klebsiella Oxytoca unique from other klebsiella species

causes AAHC

AAHC

antibiotic associated hemorrhagic colitis; swelling, vasodilation, and leaking from the bowel

________ ______ is a frequent cause of bacteremia, particularly in infants

Klebsiella oxytoca

Important virulence factors of Klebsiella oxytoca

small molecule toxins: Tilimycin and tilivaline

TM toxin name and function

Tilimycin; damages DNA → disrupts cell cycle progression of colon epithelial cells and induces apoptosis

TV toxin name and function

Tilivaline; destabilizes tubulin —> disrupts cell cycle progression and induces apoptosis

Why are TM and TV considered bonafide toxins

they are small molecules rather than a protein type toxin

Metaphor to think of Klebsiella

armored transport vehicle: does not have a strong offense of its own, but the immune systems attempts to get rid of this very hardy bacteria are responsible for many of the disease symptoms

Which klebsiella species is responsible for the majority of klebsiella infections

Klebsiella pneumoniae

What populations is klebsiella pneumoniae a particular problem for?

immunocompromised people, chronic alcoholics; commonly hospital acquired: VAPs and CAUTIs (due to the mechanical disruption of tissues)

Lung issues associated with klebsiella pneumoniae

obstruction of entire lobes and cyanosis; currant jelly sputum

what are two emerging concerns regarding Klebsiella pneumoniae

hypervirulent strains and antibiotic resistance

KPN

Klebsiella pneumoniae

what are the two lineages of KPN

classical and hypervirulent

What disease phenotypes do classical KPN strains usually cause?

• pneumonia of UTIS

• primary or secondary bacteriemias

Where are HV KPN strains geographically restricted?

Taiwan and SE Asia

What disease phenotypes does HV KPN cause

• primary pyogenic liver abscesses

• abscesses have also been observed in neck, lungs, and kidneys

• soft tissue infections (cellulitis and necrotizing fascities

• rarely can lead to meningitis

What are many KPN virulence factors related to?

reduced clearance

KPN virulence factors that contribute to reduced clearance of the bacteria

• capsule

• LPs

• fimbriae

• siderophores

• OMPs

• porins

• transporters

How are KPN strain characterized

K antigen type; K1 and K2 tend to be most virulent

How does capsule production relate to virulence?

the more capsule produced, the more virulent; non-capsular strains are non-infectious

What genetic elements are associated with KPN capsule production

RmpA and/or RmpA2 (capsule biosynthetic genes) on a plasmid; RmpA on the chromosome; RcsA and RcsB (increase capsule formation) —> there is a gene dosage effect: more genes for capsule present, the more capsule that gets produced

How does KPN avoid phagocytosis

PAMPS are covered by capsule

How does KPN avoid defensins

capsule stops them from accessing the cell surface

how does KPN avoid complement and opsonization

they cannot access the cell surface due to the capsule

How does LPS benefit Klebsiella

excludes complement components to protect the bact. from MAC and opsonization

How is LPS a liability for KPN?

activates complement through classical, alternative, and lectin pathways and also activates TLR4

What are the predominant fimbrial types in KPN

Type 1 and Type 3

What do type 1 KPN fimbrae bind

D-mannosylated glycoconjugants (bladder cells)

What are Type 1 KPN fimbrae associated with?

recurrent UTIs

Shape of Type 1 KPN fimbrae v shape of Type 3 KPN fimbrae

Type 1 are thinner, Type 3 are a little thicker with a helical structure

What do KPN Type 3 fimbrae bind to?

Collagen IV in the human ECM

When is HECM exposed and more available for binding by KPN Type 3 pili?

mechanical disruption of the epithelium or accumulation on in dwelling devices

What metal ion is required for KPN to thrive during infections

Fe

Strategies KPN emplys for acquiring iron

siderophores: small molecules that bind Fe and have specific receptors on the bacterial surface to the bacteria can take up the iron that the siderophores just collected.; the bacteria uses several types of siderophores

How does the host counteract KPN iron acquisition

some host defenses inhibit some siderophores from being taken up by the host through their specific receptor pore

What are the three clinically-relevant resistance mechanisms

• extended spectrum beta-lactamases

• AmpC beta-lactamases

  • Carbapenemases

Extended spectrum beta lactamases

exhibit beta lactamase activity against 3rd generation carbapenems in addition to activity against narrow spectrum penicillins

When are carbapenems used

reserved for severe infections that are caused by some AMR strains

Are all ESBLs carbapenemases

no

are all carbapenemases ESBLs

yes

What are AmpC Beta-lactamases

beta lactamases that function in the presence of beta-lactamase inhibitors (the inhibitors are molecules that look like beta lactams and try to soak up the beta-lactamase activity of the bacteria)

What is the literal last resort antibiotic

Kalistin