Obligatory anaerobic GN non-spore forming bacteria:

Bacteroides fragilis (BF)

Prevotella; Porphyromonas, Fusobacterium, Veilonella spp. - coccus

General characteristics GN rods/cocci pleomorphic weakly stain with Gram Habitat: upper respiratory tract intestines, genitourinary tract

Virulence factors: capsule=antiphagocytic catalase and SOD=prevent intracellular killing cytotoxic enzymes=tissue damage, induction of inflammation SCFA= prevent intracellular killing toxin – BF enterotoxin (BFT) diarrhea

DISEASES – important characteristics: Polymicrobial=difficult to treatment adjacent to mucosal surfaces (unless extends) suppurative (abscesses common) endogenous=do not spread human-to-human, opportunistic, often iatrogenic=related to invasive medical procedures tissue necrosis, abscesses, putrid odor, suppurative secretions Predisposing factors: tissue ischemia, tissue necrosis, trauma, compromised vascular supply, surgery (especially in abdomen area e.g. gut surgery, genital tract surgery)

DIAGNOSIS •Microscopy •Culture (anaerobic conditions, selective media, longer culture 48-72 hs) Identification – biochemical tests NAATs (genome sequencing) Proteomic analysis (mass spectrometry

ANTIBIOTICS active metronidazole β-lactams (carbapenems, semisynthetic penicillins with β-lactamase inhibitors) clindamycin

Upper respiratory tract via traumatic introduction and extension chronic sinusitis and otitis media, periodontal diseases • Porphyromonas • Prevotella • Fusobacterium • non-BF species

Brain abscesses via direct extension or blood (rare) • Porphyromonas • Prevotella • Fusobacterium

Intraabdominal infections via surgery, direct extension • Prevotella • BF Peptostreptococcus (GP anaerobic coccus)

Gynecologic infections via direct extension, traumatic introduction PID, abscesses, endometritis, surgical infections

• Prevotella

Skin and soft tissue infections via bite and wound contamination (myonecrosis) • BF

Blood infections bacteremia not sepsis! • BF

Gastroenteritis enterotoxin-producing strain only • BF

GN fermentative and non-fermentative rods

Fermentative GN rods intestinal GN rods facultative anaerobes of Enterobacteriaceae family

Non-fermentative GN rods obligatory aerobic rods

Opportunistic: Escherichia coli Enterobacter spp. Proteus vulgaris, mirabilis Klebsiella pneumoniae

True pathogens: Salmonella Shigella Yersinia pathogenic E. coli strain

Reservoir: environment

Transmission: inhalation, inoculation, direct contact, contact with water

Reservoir: humans and animals intestines - environment

Transmission: inhalation, inoculation via insect bite, direct contact, endogenous infections

Opportunistic: Pseudomonas aeruginosa Acinetobacter baumanii Stenotrophomonas maltophilia

Burkholderia cepacia

General characteristics: GN rods ubiquitous in nature, present in soil, water, and are part of natural (intestinal rods) or transient (non-fermentative) flora of human organism Simple nutritional requirements; ferment (fermentative rods) or oxidize (non-fermentative rods) glucose

Common virulence factors: LPS (endotoxin), adhesive fimbria, most are motile, many possess capsule

Escherichia coli

Commensal=non-pathogenic

strains endogenous (opportunistic)

infections: Urinary tract infections (UTI) =UPEC (uropathogenic E. coli) Bacteremia/sepsis Intraabdominal infections

Pathogenic strains

gastroenteritis exogenous infections

Strains divided according to virulence factors into: EPEC = enteropathogenic E. coli ETEC = enterotoxigenic E. coli EIEC = enteroinvasive E. coli EHEC = enterohemorrhagic E. coli EAEC = enteroaggregative E. coli DAEC = diffusely adhering E. coli

Predisposing factors: perforation of intestines, surgery, weakened immune system, spreading from intestines in predisposed individuals (UTI)

Reservoir: animals and humans

Transmission to humans: food-borne, direct contact

EPEC = infantile diarrhea ETEC = traveler’s diarrhea EIEC = dysentery-like diarrhea EHEC = bloody diarrhea (HC=hemorrhagic colitis) +/- HUS=hemolytic uremic syndrome +/- TTP=thrombotic thrombocytopenic purpura EAEC = chronic diarrhea DEAC = diarrhea (chronic, acute), UTI

Exception: neonatal meningitis (encapsulated K1 strains=NMEC) from mother to newborn

Diagnosis: Microscopy Culture and identification How to detect pathogenic strains?

culture + serotyping how to detect toxins?

NAATs Virulence factors: (all present specific adhesion fimbria) EPEC - intimin+Tir = tight adherence to enterocytes ETEC – LT, ST enterotoxins EIEC – invasin EHEC – shiga toxin EAEC – cytotoxins and enterotoxins, adhesins DAEC = invasion, specific adhesins

Treatment: generally all infections caused by GN rods should be treated according to antimicrobials susceptibility

testing

Groups of antimicrobials active against GN rods: β-lactams, aminoglycosides, fluoroquinolones, TMP-

SMX etc.

Important! EHEC infections should not be treated with

antimicrobials

Yersinia – zoonotic infections

Y. pestis plague

Reservoir: rodents (rats, squirrels, rabbits, domestic animals)

Transmission to humans: flea bite (VECTOR), air-borne,

direct contact with animal tissue

Y. enterocolitica enterocolitis (mesenteric

lymphadenitis=pseudoappendicitis) Y. pseudotuberculosis

enterocolitis, Far East Scarlet-like Fever

Reservoir: animals

Transmission to humans: food-borne, blood transfusion

Complications: erythema nodosum reactive arthritis septicemia intraabdominal abscesses

PLAGUE bubonic (buboes) – flea bite (75% mortality) pneumonia – inhalation (>90%

m

VIRULENCE FACTORS LPS Intracellular survival (invasive bacteria) Resistance to phagocytosis Protein capsule Serum resistance Enzymes disturbing blood clotting

ortality) blood infection

septicemia

PLAGUE bubonic (buboes) – flea bite (75% mortality) pneumonia – inhalation (>90% m

VIRULENCE FACTORS LPS Intracellular survival (invasive bacteria) Resistance to phagocytosis Protein capsule Serum resistance Enzymes disturbing blood clotting

ortality)

VIRULENCE FACTORS LPS Intracellular survival (invasive bacteria) Resistance to phagocytosis Protein capsule Serum resistance

Enzymes disturbing blood clotting

TREATMENT Cephalosporins Aminoglycosides Chloramphenicol Tetracyclines

TMP-SMX

DIAGNOSIS Microscopy Culture – cold-tolerant Serotyping

TREATMENT Streptomycin Chloramphenicol Tetracyclines

TMP-SMX

SALMONELLA

Typhoid fever Gastroenteritis Gastroenteritis

S. Typhi, S. Paratyphi S. Choleraesuis S. Typhimurium, S, Enteritidis

BLOOD INFECTON (septicemia)

Reservoir: HUMAN only !!! Reservoir: animals, humans Reservoir: animals, humans

Transmission: person-to-person fecal-oral route

long-lasting carriage (gallbladder)

Transmission: fecal-oral route food-borne

Virulence factors: LPS Vi capsule

Enterotoxin Cytotoxin

Virulence factors: LPS, enterotoxin

Gallbladder - bile

Small intestine Invasion via M cells

(Payer patches)

Mesenteric lymph nodes - blood

Liver, spleen, bone marrow

High fever, rash

Shigella

Sh. dysenteriae – dysentery (shiga toxin) HUS

developing countries Sh. sonnei Sh. flexneri shigellosis – bloody diarrhea

Sh. boydii world-wide distribution

Transmission: person-to-person (fecal-oral route)

Reservoir: humans only !!!

Miscellaneous intestinal rods

Opportunists – endogenous infections

Proteus, Enterobacter, Citrobacter, Morganella, Serratia

Hospital-acquired (nosocomial) infections in newborns and immunocompromised

Klebsiella

K. pneumoniae: community-acquired (CA) necrotizing pneumonia Wound, soft tissue infections, UTI

K. granulomatis: sexually transmitted (SDT) or via traumatic introduction granuloma inguinale (donovanosis)

K. rhinoscleromatis and K. ozenae: chronic atrophic rhinitis (uncommon)

Pseudomonas aeruginosa

General characteristics: aerobic, ubiquitous in nature, produces pigments, not-fastidious, transient colonizer of upper respiratory tract, skin and gastrointestinal

tract in humans, inherently resistant to many antibiotics; treatment – combined therapy e.g. β-lactams+aminoglycosides; OPPORTUNITIC PATHOGEN

Virulence factors: capsule – antiphagocytic LPS toxic enzymes: proteases, phospholipase C, exoenzymes S and T – tissue damage, hemolysis pigments (pyocyanin) – induce inflammation EXOTOXIN A – inhibits host cell protein synthesis – kills host cells

Diseases: RTI: inhalation, intubation – tracheobronchitis, necrotizing bronchopneumonia Skin and soft tissue infections: traumatic inoculation, contamination – wounds (burns), hot tube folliculitis, ecthyma gangrenosum (during bacteremia) Bones: spreading from wound infection – osteochondritis UTI: in patients with urinary catheters Blood: blood catheters, contaminated infusion fluids – bacteremia, endocarditis Ear: contact with contaminated water – swimmer ear, malignant otitis externa Eye: traumatic inoculation (contact lenses) – corneal ulceration

Burkholderia Stenotrophomonas maltophilia Acinetobacter baumanii

OPPORTUNISTIC PATHOGEN B. cepacia – pneumonia, UTI, bacteremia B. pseudomalei (endemic Asia, Africa) –

inhalation, direct contact with soil, water, ingestion, traumatic inoculation: melioidosis (glanders); suppurative

cutaneous infections Susceptible to TMP-SMX

OPPORTUNISTIC PATHOGEN Pulmonary and blood infections traumatic inoculation (catheter),

contaminated infusion fluids, intubation, Uniformly resistant to carbapenems Susceptible to TMP-SMX

OPPORTUNISTIC PATHOGEN Pulmonary, wounds, blood infections – traumatic inoculation (catheter),

contaminated infusion fluids, intubation, wound contamination

Melioidosis (glanders) a rare contagious disease that mainly affects horses, characterized by swellings below the jaw and mucous discharge from the nostrils,

but may present generalized symptoms

Burkholderia pseudomalei - meloidosis

Answer questions – lecture 5; class 6 and 7: Non-spore forming anaerobes, fermentative and non-fermentative Gram-negative rods.

For all bacterial groups and species students should know: their habitats (reservoirs), sources and ways of transmission to humans, means of prevention

1. Name bacteria genera belonging to non-spore-forming anaerobes

2. What is the reservoir of non-spore forming anaerobes

3. What diseases non-spore forming anaerobes can induce?

4. Name virulence factors of non-spore forming anaerobes

5. What are factors predisposing to diseases caused by non-spore forming anaerobes

6. What are common characteristics of infections caused by anaerobes?

7. Name genera of bacteria included in Enterobacteriaceae family

8. Which genera of Enterobacteriaceae family include strict human pathogens?

9. What is the reservoir of GN fermentative rods?

10. How they are transmitted to humans?

11. Name virulence factors common to all GN fermentative rods

12. Name ways of transmission of GN fermentative rods strictly pathogenic to humans

13. Name pathovars (pathotypes) of E. coli pathogenic to humans

14. Name extraintestinal infections caused by E. coli

15. Name reservoirs and ways of transmission of E. coli strains causing intestinal infections in humans

16. Name exotoxins produced by E. coli causing intestinal infections in humans

17. Name Salmonella species and diseases they produce

18. Name reservoirs and ways of transmission of Salmonella species

19. What are virulence factors produced by Salmonella?

20. Explain patomechanism of typhoid fever

21. What patient’s samples should be send to the laboratory in case of salmonellosis and typhoid fever?

22. Name Shigella species

23. What is the reservoir of Shigella?

24. What are ways of transmission of Shigella to humans?

25. Name virulence factors of Shigella

26. What is a severe complication of shigellosis? Explain patomechanism

27. Name opportunistic species of Enterobacteriaceae family and diseases they produce

28. Name Klebsiella species and diseases they can produce in humans

29. Name Yersinia species and diseases they cause

30. Name reservoirs and routes of transmission of Yersinia species

31. What is reservoir of plague?

32. What are types of plague and how humans can acquire these types?

33. What disease is produced by Y. enterocolitica and Y. pseudotuberculosis?

34. What is the reservoir and the route of transmission of Y. enterocolitica to humans?

35. Name clinically important GN non-fermentative rods

36. Name virulence factors of Pseudomonas aeruginosa

37. Name diseases/infections caused by Pseudomonas aeruginosa

38. Why GN non-fermentative rods are considered opportunistic pathogens?

39. Name clinically important species of Burkholderia?

40. Characterize Stenotrophomonas maltophilia and Acinetobacter baumanii species