O'Donnell Gram Negative Pathogens

One type of bacteria can often cause multiple diseases based on:

The location in the host and virulence factors

What types of bacteria are associated with STIs?

Chlamydia

Neisseria

• Not N. meningitidis

Chlamydia trachomatis

Pleiomorphic, intracellular, gram negative

Most common bacterial STI in the US

Most cases are asymptomatic (“silent” disease)

In women, initially infects the cervix and urethra

• Can spread to fallopian tubes or uterus → Pelvic Inflammatory Disease (PID) → can lead to infertility

Antibiotic resistance is uncommon

No vaccine

Neisseria gonorrhoeae

Gram negative diplococci

2nd most common STI in the US → non-sexual transmittion is rare

Localised mucosal infection, rarely in blood

Test by PCR along with chlamydia

• Specific test for the DNA of the bacteria

95% of men and 50% of women are symptomatic

Can lead to Epididmitis in men and Pelvic Inflammatory Disease in women

Risk of spread is up to 50% (very high for an STI)

Lots of penicillin resistance

No effective vaccine (due to antigenic variation)

Why are gonorrhea and chlamydia tested for at the same time using a PCR test? 

They have similar symptoms, and it is difficult to gram stain chlamydia

Neisseria meningitidis

Gram negative diplococci

NOT an STI

Causes meningitis

• Infect bloodstream or CNS

• Fever, headache, seizures, inflammation, increased cranial pressure-

• Mostly infants and age 18-20

Person to person spread via respiratory route

Can also cause endotoxic shock (released of LPS)

Protect themselves from immune response by incorporating host sugars in the outer membrane to look like host cells

Has a vaccine

Similarities and differences between strains of Neisseria

Both attach with pili and OMPs (outer membrane proteins)

Both express LPS

N. gonnorrhoeae

• No capsule

• Localized infection

N. meningitidis

• Capsule → more invasive

• Systemic infection

Meningitis

Infection and inflammation of the meninges, or membranes around the brain and spinal cord

Neisseria meningitidis vaccine recommendations

First dose recommended at 11 years old

Recommended as early as 2 months old for high risk infants

Booster at 16 years old

• Protects students entering college or the military

What types of bacteria are associated with respiratory infections?

Haemophilus

Bordetella

Moraxella

Legionella

Haemophilus Bacteria

Gram negative coccobacilli

Only found in people

Part of the normal flora in many people

Haemophilus influenzae

Can cause respiratory and sinus infections, otitis media, and conjunctivitis (NOT what causes seasonal influenza)

Most virulent strains have capsules

• Can invade the CNS (meningitis) and the joints (arthritis)

6 serotypes (A-F)

• Different capsules and surface polysaccharides

Haemophilus influenzae Serotype B (Hib)

Most virulent

Capsule includes a polysaccharide called polyribitol phosphate (PRP)

• Vaccine designed against PRP

  • Recommended at 2 months of age

Bordetella pertussis

Gram negative coccobacilli

Destroys cilia in the respiratory tract

Causes whooping cough

• Infants at highest risk

Pertussis toxin

• A-B exotoxin

Antibodies against pertussis toxin prevent colonization of the bacteria

DTaP Vaccine

• Diphtheria, Tetanus, acellular Pertussis

DTaP Vaccine Schedule

2 months, 4 months, 6 months, 15-18 months, and 4-6 years

Booster at 11-12 years

Complications from whooping cough

Nose bleeds and ear infections

Pneumonia

Brain damage

• Mental impairment

• Seizure disorders

Cerebral hemorrhage

Death

Moraxella catarrhalis

Gram negative diplococci

Mostly associated with localized infections like pneumonia, bronchitis, otitis media

• Commonly causes lower respiratory tract infections in elderly patients with other pulmonary conditions

Frequent β-lactamase producer

• Often found with other bacteria, since β-lactamase release can protect other bacteria in the area

Legionella pneumophila

Intracellular gram negative bacilli

Ubiquitous in fresh water and plumbing

• Lives within amoebas, protozoa

Causes necrotizing multifocal pneumonia

• Infects alveolar macrophages, taking control of the ribosomes and mitochondria

• High mortality (15-50%)

  • Respiratory failure, shock

  • Most often seen in immunocompromised and elderly patients

Person to person transmission has not been shown

Necrotizing Multifocal Pneumonia

Inflammation of the lungs and death of lung tissue in multiple areas of the lung

What types of bacteria are associated with gastrointestinal infections?

Straight gram negative rods

• Enterobacterales

Curved gram negative rods

• Vibrio

• Campylobacter

• Helicobacter

Enterobacterales

Straight gram negative bacilli

Large family of enteric bacteria

• Main pathogens are:

  • Escherichia coli

  • Klebsiella

  • Proteus

  • Shigella

  • Salmonella

Especially problematic if they escape the digestive tract

Facultative anaerobes

Shigella and salmonella are very similar genetically and are spread by _____

Contaminated food and fecal-oral route

Key lab finding for E. coli and Klebsiella

Lactose positive

• Can ferment lactose

Escherichia coli

Over 700 different strains

Most common infections:

• Food poisoning/diarrhea (gastroenteritis)

• Urinary tract infections

Also associated with more invasive infections including:

• Pyelonephritis (UTI that spread to kidney)

• PID

• Pneumonia

• Meningitis

Prevention is key for all strains

Classification of E. coli

Classified by surface antigens - important for tracking the origin of outbreaks

• H antigens: flagella

• O antigens: LPS

• K antigens: capsule

• Ex. O157:H7 - found in cow intestines, common source of outbreaks

Classified according to virulence

1. Enteropathogenic (least invasive)

2. Enterotoxic

3. Enteroinvasive

4. Enterohemorrhagic (most invasive)

Enteropathogenic E. coli

Adheres to gut, but doesn’t enter cells

Destroys surface microvilli

Causes diarrhea and vomiting

Injects proteins into the cell, forcing actin rearrangement into pedestal shape

Enterotoxic E. coli

Produces exotoxins

• Cholera-like toxin - causes release of water and iron from cells

• Heat-stabile toxin - prevents uptake of water and iron from cells

Overall effect: severe diarrhea and vomiting

Enteroinvasive E. coli

Actually invades/enters cells

Causes dysentary

• Damages cells of the digestive tract, often killing them

• Often leads to bloody diarrhea and fever

More likely to be fatal

Mostly seen in kids under 5

Enterohemorrhagic E. coli

Doesn’t stay in intestinal tract

Produces an exotoxin from Shigella

Gets into bloodstream and causes systemic infection

• Attacks kidneys (kidney failure)

• Can cause descending UTIs

• Anemia (exotoxins kill red blood cells)

• Hemorrhagic diarrhea

• Combination of symptoms called Hemolytic-uremic Syndrome (Anemia-kidney failure)

Most common cause of acute kidney failure in children

Ex. O157:H7

Klebsiella pneumoniae

Normal part of gut flora

• Doesn’t usually cause disease in health people

Cause of healthcare associated infections

• Pneumonia, bloodstream infections, surgical site infections, meningitis

Becoming very resistant to antibiotics

Carbapenem-resistant Enterobacterales (CRE)

Group of bacteria that are resistant to carbapenems

Caused by plasmids that carry genes for particular enzymes

• KPC (Klebsiella pneumoniae carbapenemase) - most widespread in US

• NDM (New Delhi Metallo-beta-lactamase)

• Oxa-48 (Oxacillinase-48)

Proteus Bacteria

Gram negative bacilli

Lactose negative

Normal part of gut flora

Becomes a problem if it enters the urinary tract

• Most common cause of hospital-acquired UTIs

• Associated with urinary stones and complicated UTIs

Very good at immune invasion

Proteus mirabilis

Most common Proteus bacteria

They can “swarm”

• Lots of flagella

• Move over viscous and solid surfaces

• Issue for urinary catheters, movement to kidneys

Sulfur/rotten egg smell

Campylobacter jejuni

Gram negative curved/spiral bacilli

Microaerophile

Leading cause of gastrointestinal illness in developed countries

• Contaminated food (raw chicken)

Causes diarrhea and dysentary

Usually self-limiting, but antibiotics are required if it escapes the digestive tract

May lead to Guillain-Barré Syndrome

Guillain-Barré Syndrome

Generally proceeded by an infection

Demyelinating neuropathy

Surface antigen on C. jejuni resembles gangliosides on peripheral myelin

• The immune response mistakenly attacks myelin

  • Cross reactive antibodies → detect more than one thing

Therapy for Guillain-Barré Syndrome

Plasmapheresis

• Filters out antibodies from bloodstream

  • Removes cross-reactive antibodies and quiets immune response

High dose immunoglobulin therapy

Helicobacter pylori

Gram negative curved or spiral bacilli

Microaerophile

Limited to the stomach

• Produces urease

  • Allows the bacteria to persist in low pH

Associated with many gastric ulcers

• Antibiotic treatment is common now

May also be associated with gastric cancer

• Chronic inflammation in the gut may lead to rapid turnover of cells

• Link between inflammation and cancer

Zoonosis

Disease primarily of animals that can be transmitted to humans due to direct or indirect contact with infected animals

Yersinia pestis

Gram negative bacilli, zoonotic

Facultative anaerobe

Cause of the Black Death or Bubonic Plague

Killed 1/3 of Europe’s population in the middle ages

• Less concern today due to better sanitation

• Still occasional cases in the southwestern US through encounters with infected rodents or fleas

Concerns due to possible use for bioterrorism

• Potential for person to person spread in densely populated urban areas

SPACE Organisms

5 gram negative bacteria that are opportunistic, found in healthcare settings, and have antibiotic resistance

Pseudomonas aeruginosa

Aerobic gram negative bacilli

Most common SPACE bacteria

Most often seen in patients with another illness/injury

Produces Toxin A

• Prevents protein translation in host cells

Characterized by the formation of a dark blue pigment, pyocyanin

Forms biofilms in the lung

• Problem for cystic fibrosis patients

• Leads to chronic infection, greater inflammation, and higher antibiotic doses (100-1000x the MIC)

  • Once biofilm is established → difficult to get rid of

Pseudomonas aeruginosa is most often seen in patients with another illness/injury such as:

Burns and wounds

• Destruction of blood vessels

• Phagocyte access is limited

Cancer

• Chemotherapy destroys the immune system

Cystic fibrosis

• Altered respiratory epithelium

• Pneumonia

Acinetobacter baumannii

Gram negative pleiomorphic SPACE bacteria

Induces apoptosis of infected cells

Resistant to complement tagging

Forms biofilms

Multiple invasive disease states

• Meningitis, wound infection, bloodstream infections, pneumonia

Recent emergence of multi-drug resistant (MDR) and pan-drug resistant (resistant to everything we have) strains

Bacteroides fragilis

Opportunistic gram negative bacilli

Obligate anaerobe

Part of gut flora, not invasive on its own

• Can even be helpful, people with this bacteria often have lower levels of inflammation in the gut

• Damage/trauma to intestines can allow it to escape and cause abdominal abscesses

• Most commonly isolated bacteria from anaerobic infections

Positive role

• May prevent colitis or inflammatory bowel disease

  • Produces polysaccharide A, which inhibits inflammation

_____ bacteria are most concerning and highest priority in terms of drug resistance

Gram negative