GENERAL CHARACTERS OF MEDICALLY IMPORTANT BACTERIA THE ENTEROBACTERIACEAE

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1 GENERAL CHARACTERS OF MEDICALLY IMPORTANT BACTERIA THE ENTEROBACTERIACEAE Presented by: Dr: lamiaa adel Assistant professor of Medical Microbiology and Immunology

2 Intended Learning Outcomes By the end of this lecture students should be able to: Mention important biological properties of Escherichia, Klebsiella, Proteus, Salmonella, Shigella List their mode (s) of transmission. Describe the role of their virulence factors of in relevant infections. Enumerate clinical diseases caused by them.

3 The Enterobacteriaceae is a very large family of Gram negative bacilli.

4 Enterobacteriacae family includes many genera as: Escherichia, Klebsiella, Enterobacter, Serratia, Proteus, Providencia, Morganella, Salmonella, Shigella & Yersinia

5 Natural Habitat: 1.The majority are present as the normal flora in the colon of both man and animals (e.g. E. coli). 2.Some are saprophytes in water, soil and plants (e.g. Proteus). 3.Few of them are primarily intestinal pathogens (e.g. Salmonella & Shigella )

6 Characterized By Motile with Peritrichate flagellae e.g. E.coli Salmonella and Proteus or non motile e.g. Klebiella & Shigella Same morphology Gram-ve bacilli non spore forming Differ in capsule and motility They grow on ordinary media & and selective and differential media

7 Enterobacteriaceae have 4 common characteristics Facultative anaerobes Ferment sugars either or Catalase + oxidase - Reduce Nitrate to nitrite

8 Surface antigens of Enterobacteriaceae Somatic O antigen (LPS) Flagellar H antigen Capsular K antigen

9 GENUS ESCHERICHIA

10 This genus contains five species, the most important of which is Escherichia coli (E.coli). E. coli ferments lactose, a property that distinguishes it from the two major intestinal pathogens, Shigella and Salmonella.

11 Normal habitat: 1. Gut of humans and animals; it is the most abundant facultative anaerobe in the colon and feces. 2. It may colonize lower end of urethra and vagina.

12 The antigenic structure

13 Virulence Factors: Pili. Capsule. Endotoxin. Three exotoxins (enterotoxins). Motility.

14 Diseases caused by Escherichia coli 1- Urinary tract infection (UTIs) Caused by uropathogenic E. coli E.coli is the most common cause of UTI. 2- Neonatal meningitis: caused by strains having K1 type capsular antigen. 3-Health care associated infections SSI, CAUTI, VAP and intravascular device associated infections

15 4- Diarrhea: caused by certain strains known as diarrheagenic E. coli. Diarrheagenic E. coli: 1.Enterotoxigenic E. coli (ETEC). 2.Enterohaemorrhagic E. coli (EHEC). 3.Enteropathogenic E. coli (EPEC). 4.Enteroinvasive E. coli (EIEC). 5.Enteroaggregative E. coli (EAEC)

16 Pathogenesis of E.coli infections: Source of the E. coli Diarrhea is acquired by ingestion of food or water contaminated with human feces. Urinary tract infections the patient s own colonic flora that colonizes the urogenital area. Neonatal meningitis the mother s birth canal; the infection is acquired during birth.

17 Enterotoxigenic E. coli (ETEC): Produce 2 enterotoxins: heat labile (LT) and heat stable (ST) toxin The heat-labile toxin (LT) stimulate adenylate cyclase intracellular camp outpouring of fluid, K +, Cl - from the enterocytes into the lumen of the gut Watery diarrhea. heat-stable toxin (ST) stimulate guanylate cyclase intracellular cgmp Watery diarrhea.

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19 Enterohaemorrhagic E. coli (EHEC) or Verotoxigenic E. coli (VTEC) produce Shiga - like toxins called verocytotoxins (VT) similar in action to Shiga toxin. They act by inhibition of protein synthesis causing bloody diarrhea

20 Enteropathogenic E. coli (EPEC) Pathogenicity is due to adherance to enterocytes by a special type of pili leading to destruction of microvilli, electrolytes imbalance and watery diarrhea.

21 Mucosal damage results in malabsorption & profuse watery diarrhea

22 Enteroinvasive E. Coli (EIEC) EIEC cause disease dysentery like syndrome. Virulence factors are nearly identical to Shigella species; that allow the invasion of mucosal epithelial cells of the large intestine and intracellular spread Tissue destruction diarrhea, blood, mucous, and painful abdominal cramps (similar to shigella dysentery).

23 Enteroaggregative E. coli (EAEC) Characterized by specific pattern of adherenc to intestinal cells in an aggregative manner by aggregative adhrence fimbriae and production of heat stable (ST)-like toxin. EAEC causes traveller s diarrhea and persistent diarrhea in children.

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25 Pathogenesis of Neonatal meningitis & sepsis: E.coli strains with K1 capsular antigen acquired by neonate through passage in birth canal invade the blood stream of infants from the nasopharynx or gastrointestinal tract causing sepsis and meningitis.

26 Pathogenesis of Urinary Tract Infections: The bacteria colonize the periurethral area then ascend the urinary tract to cause UTI. Pili bind to specific receptors on the urinary tract epithelium. Motility aids to ascend from: Urethra into the bladder. Ureter into the kidney.

27 A 7-year-old female child is taken to an urgent care facility because of fever and periodic incontinence. The physician suspects a urinary tract infection. What is the most likely etiology of this child s infection? (A) Escherichia coli (B) Proteus mirabilis (C) Pseudomonas aeruginosa (D) Staphylococcus saprophyticus (E) Ureaplasma urealyticum

28 A 35-year old male became ill with watery diarrhea due to a bacterial infection while on a trip to South America. Which of the following is the key event that promotes the development of watery diarrhea (A) Decreased activity of adenylate cyclase (B) Increase in the epithelial cell levels ofcamp (C) Increase in the levels of intracellular chloride (D) Movement of water from the intestinal lumen into the epithelial cells. (E) Movement of ions such as potassium and sodium into the intestinal epithelial cells

29 Genus Klebsiella

30 GENUS KLEBSIELLA The Klebsiella genus is part of the Enterobacteriaceae family. Klebsiella spp. : o short gram negative rods. o non motile. o capsulated (polysaccharide). Habitat: is the human large intestine and upper respiratory tract.

31 Antigenic structure The genus Klebsiella generally display two types of antigens on the surface of the cell: 1. Capsular polysaccharide (K antigen) :80 types. 2. Lipopolysaccharide (O antigen) :

32 Species Two species produce diseases in man; can be differentiated by their capsular antigens. Klebsiella pneumoniae Klebsiella oxytoca

33 Klebsiella pneumoniae The most common species responsible for majority of infections Includes 4 subspecies: K. aerogenes, K. pneumoniae K. ozanae, K. rhinoscleromatis

34 Diseases: 1.Community-acquired pneumonia: Necrosis, inflammation, and hemorrhage occur within lung tissue, sometimes producing thick, bloody, mucoid sputum described as currant jelly sputum ( Fried-Lander pneumonia)

35 The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. Fried-Lander Pneumonia

36 2. Health care associated infections (majority of Klebsiella infections) e.g. pneumonia, UTI and SSI. 3. Neonatal bacteremia & septicemia especially among premature infants and in neonatal intensive care units. Neonatal Meningitis

37 Transmission: 1.Organism is transmitted to the lungs by aspiration from upper respiratory tract or by inhalation of respiratory droplets. 2.It is transmitted to urinary tract by ascending spread of fecal flora. 3.It is transmitted in hospitals by contact by contaminated hands of surrounded people in the hospitals or contact with contaminated equipment in hospitals e.g. catheters, respiratory devices.

38 Virulence factors: 1.The huge polysaccharide capsule: It is the main virulence factor. It is antiphagocytic. 2.Lipopolysaccharides (LPS): fever and shock associated with sepsis. 3.Adhesins: These may be fimbrial or nonfimbrial. These help the microorganism to adhere to host cells.

39 Genus Proteus

40 GENUS PROTEUS oproteus species are part of the Enterobacteriaceae family. othey are gram-negative highly motile bacilli. produces a striking swarming effect on some culture media as blood agar. o Proteus species are found in: soil and water and human colon

41 The genus Proteus is characterized by: Rapid urease activity ( within 4 hours) Cleave urea to ammonia &CO2 Swarming motility on nutrient and blood agar

42 Antigenic structure 1. Somatic O antigen: : 2. Flagellar H antigen:

43 Virulence Factors 1.The flagellum Vigorous motility contribute to the ability to invade the urinary tract. 2.Pili responsible for adhesion. 3. Endotoxins responsible for induction of the inflammatory response.

44 4. Urease responsible for raising the ph which allows stone formation to take place.stones can obstruct urine flow, damage urinary epithelium, and serve as a nidus for recurrent infection by trapping bacteria within the stone.

45 Endotoxin Pili Urease Flagella

46 Mode of transmission: 1.Proteus spp. are part of the human intestinal flora and can cause infection upon leaving this location. 2.They may also be transmitted through contaminated catheters (particularly urinary catheters).

47 Diseases: These organisms primarily cause urinary tract infections, both community- and hospitalacquired. Other infections: septicemia and wound infections.

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49 Genus Salmonella Characters Gram-negative, motile non-sporing rods, non-capsulated except Salmonella typhi (S. typhi) and S.paratyphi C which possess Vi antigen.

50 Natural habitat All salmonellae are obligate parasites. Man is the only reservoir for S.typhi whereas other species of salmonellae are parasites of animals most frequently poultry and eggs.

51 Antigenic structure 1. Somatic O antigen: serogroups. 2. Flagellar H antigen: These O serogroups are further divided into serotypes according to H antigen. 3. Some possess Vi ( capsular) antigen.

52 Virulence factors of Salmonellae include: 1. Fimbriae: attachment to host cells. 2. Intracellular pathogen: can survive & multiply within macrophages. 3. Capsule (Vi) of S. typhi and S.paratyphi C, which is antiphagocytic. 4. Phase variation of H antigens, which varies from group (phase II) to species specific (phase I). This variation helps the organism to evade the immune system.

53 Diseases Enteric fever : Salmonella typhi, S. paratyphi A,B,C. Enterocolitis (Food poisoning): S. typhimurium, S. enteritidis. Bacteremia with focal lesions in bones, Lungs and meninges: Salmonella cholera suis.

54 Typhoid fever: Transmission Ingestion of contaminated food or water by the excreta of a case or carrier (fecal or urinary carrier).

55 Pathogenesis of enteric fever

56 Salmonella food poisoning "Salmonella Enterocolitis" 1.Inadequately cooked poultry and eggs (common source) or meat products. 2.Contaminated food by excreta of animals e.g. rats. 3.Human sources: patient during enterocolitis attack or chronic carriers.

57 Invasion of the small and large intestines. Resulting in inflammation and diarrhea. Neutrophils limit the infection to the gut and the adjacent mesenteric lymph nodes; bacteremia is infrequent in enterocolitis.

58 Salmonella Bacteremia with Focal Lesions Transient or persistent bacteremia. Mode of transmission of focal lesions: by Blood Bacteremia with localized foci resulting in persistent infection of many organs with osteomyelitis, pneumonia, and meningitis as the most common sequelae.

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60 Shigella Morphology: Shigellae are Gram negative bacilli Non motile, non capsulated, Facultative anaerobe. Shigella is a true human pathogen, for which there is no animal reservoir.

61 Classification: The genus Shigella has 4 species or subgroups (A, B, C, and D) & several serotypes. Subgroups and serotypes are differentiated from each other by their biochemical characteristics and antigenic properties. 1-Group A: shigella dysenterae 2-Group B: Shigella flexneri 3-Group C: Shigella boydii 4-Group D :Shigella sonnei

62 Virulence of Shigellae: 1. Attachment & penetration of mucosal epithelial cells of large intestine. 2. Intracellular spread proteins: facilitate transfer of bacteria to adjacent cells.

63 Virulence of Shigellae (cont.) 3. Shiga toxin: It is produced by Shigella dysenteriae type 1. It has the following characters: a.enterotoxic, neurotoxic and cytotoxic activity. b.encoded by chromosomal genes. c.similar to the Shiga-like toxin of enterohemorrhagic E. coli (EHEC) 0157:H7 strain except that Shiga-like toxin is encoded by lysogenic bacteriophage.

64 Shiga toxin cytotoxic activity: Damage to epithelial cells of intestine: Inhibit protein synthesis, causing cell death, vascular damage to the intestine, and hemorrhage (blood and fecal leukocytes in stool). Damage to glomerular endothelial cells, leading to haemolytic uremic syndrome (HUS).

65 Disease: Bacillary Dysentery Shigella dysenteriae causes the most serious form of bacillary dysentery.

66 Pathogenesis of Bacillary Dysentery: Transmission Shigella is one of the most infectious of bacteria and ingestion of as few as 10 organisms will cause disease.

67 It is transmitted by: 1.Feco-oral route (main route) e.g. ingestion of contaminated food and water. 2.Contact with infected object. The bacteria reach submucosa of the large intestine. Macrophages take up bacteria, die and release the organism.

68 The bacteria spread to adjacent cells Death of infected cells. Shigella dysentery manifested by diarrhea, blood, mucous, and painful abdominal cramps. Shigellae infection does not lead to bacteremia.

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70 Medical physicians, working in a camp in central Africa, are concerned with number of young children presenting with high fever, bloody diarrhea, and dehydration. The suspected organism is described as a non-motile, Gram-negative bacillus that does not produce lactose-positive colonies on selective media. Based on these findings, which disease is more likely? 70

71 (A) Bacillary dysentery (B) Campylobacteriosis (C) Cholera (O:1 classic biotype) (D) Nontyphoidal salmonellosis (E) Staphylococcal food poisoning

72 A major virulence factor of the etiologic agent in theabove question is a toxin. What is the role of this toxin in disease production? (A) Acts as a superantigen thereby inducing inflammation (B) Blocks protein synthesis causing intestinal cell death (C) Increases camp concentration within intestinal cells (D) Increases cgmp concentration within intestinal cells (E) Suppresses cytokine secretion by immune cells

73 73 Microbiology & Immunology Department