A guide to pathogenic bacteria

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1 Pathogens Also known as: Pathogenic organisms Infectious agents Germs Biological agents that cause disease Groups of pathogens: Bacteria Viruses Fungi Parasites Opportunistic pathogen A biological agent that cause disease when there is a window of opportunity

2 A guide to pathogenic bacteria

3 Main divisions of bacteria Gram-positive division Gram-negative division Spirochaetes Acid-fast bacilli Mycoplasmas, rickettsiae & chlamydiae

4 Comparison of the cell walls of Gram positive and negative bacteria Outer membrane Periplasmic space Inner membrane Cell Wall Cell Wall Membrane Gram negative Gram positive

5 Gram s Stain

6 Gross morphology Microscopic Between 0.5 and 2.0 μm in diameter Shapes Arrangement of bacterial cells

7 Bacterial cell shapes Coccus Rod (Bacillus) Spiral and curved Rod

8 Arrangement of Bacterial Cells

9 Gram Stain Positive Negative e.g. cocci rods e.g. cocci rods Staph. aureus Neiserria gonorrhoea Strep. pneunomiae Neiserria meningitidis e.g. Bacillus anthracis Clostridium spp. Corynebacterium diphtheriae straight e.g. Escherichia coli simple curved spiral e.g. Vibrio cholerae Vibrio parahaemolyticus e.g. Borrelia burgdorferi Treponema pallidum

10 Some scientists do not classify spirochetes with Gram s stain. The spirochetes are not classified as either Grampositive or Gram-negative. When Borrelia burgdorferi is Gram-stained, the cells stain a weak Gram-negative by default, as safranin is the last dye used. Borrelia, like most spirochetes, does have an outer membrane that contains an LPS-like substance, an inner membrane, and a periplasmic space which contains a layer of peptidoglycan. Therefore, it has a Gram-negative bacterial type cell wall, despite its staining characteristics. (

11 Gram positive cocci Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes

12 Gram positive rods Bacillus anthracis Clostridium tetani Corynebacterium diphtheriae Not Gram Stain

13 Gram negative cocci Neisseria gonorrhoeae Neisseria meningitidis

14 Gram negative rods Straight E.coli Simple Curved Vibro cholerae Not Gram Stain Spiral Borrelia burgdorferi Not Gram Stain

15 Staphylococci Gram positive cocci in cluster (35 species and 17 subspecies) Staph. aureus Staph. epidermidis Staph. saprophyticus Coagulase negative staphylococci

16 An opportunistic pathogen Staph. aureus Causes pyogenic (pus-producing) infection Skin lesions (e.g. furuncles, styes) Deep-seated infection Osteomyelitis; arthritis; breast, cerebral, pulmonary, and renal abscesses; pneumonia etc. Bacteremia Endocarditis in I.V. drug absusers Staphylococcal enterocolitis due to broad-spectrum antibiotic treatment Major cause of hospital acquired (nosocomial) infection of surgical wounds Causes toxic shock syndrome in young women(associated with the usage of highly absorbant intravaginal tampon) Produces heat stable enterotoxins - causes food poisoning

17 Bacteria commonly found on the surfaces of the human body BACTERIUM Skin Conjunctiva Nose Pharynx Mouth Lower GI Ant. urethra Vagina Staphylococcus epidermidis Staphylococcus aureus* + +/ /- + Streptococcus mitis /- + + Streptococcus salivarius Streptococcus mutans* + ++ Enterococcus faecalis* +/ Streptococcus pneumoniae* +/- +/ /- Streptococcus pyogenes* +/- +/ /- +/- Neisseria sp. * Enterobacteriaceae*(E. coli) +/- +/- +/ Proteus sp. +/ Pseudomonas aeruginosa* +/- +/- + +/- Haemophilus influenzae* +/ Bacteroides sp.* /- Bifidobacterium bifidum ++ Lactobacillus sp Clostridium sp.* +/- ++ Corynebacteria Mycobacteria + +/- +/- + + Actinomycetes + + Spirochetes Mycoplasmas / = nearly 100 percent + = common (about 25 percent) +/- = rare (less than 5%) * = potential pathogen (Modified from

18 Normal flora in the nasal cavity Staphylococcus epidermidis Staphylococcus aures* Streptococcus pneumoniae* Neisseria sp. Neisseria meningitidis * Enterobacteriaceae* Proteus sp. Haemophilus influenzae* Corynebacteria Mycobacteria* / / /- * potential pathogen ++ frequent + common +/- rare

19 Mechanisms of Bacterial Pathogenicity Host Defense Mechanisms

20 Coagulase Staph. aureus produce coagulase a bacterial defense mechanism Clot the areas of plasma around them Enable them to resist phagocytosis by the host's immune system

21 Staph. aureus Staph. aureus Staph. epidermidis s/images/macstaph.jpg

22 Furuncle Stye Video - histopathology of furuncle v=gdrvv7ojxyy Abscess mages/abscess_lg.jpg

23 Staph. epidermidis causes infections associated with indwelling medical devices. Staph. saprophyticus causes urinary tract infections, especially in girls (10 20 % of urinary tract infections in girls).

24 Coagulase tube test

25 Coagulase tube test Staphylococci (35 species and 17 subspecies) Coagulase tube test positive negative In human In animal Staph. aureus Staph. intermedius Staph. hyicus Coagulase negative staphylococci (CNS or CoNS)

26 MRSA MRSA refers to methicillin resistance Staphylococcus aureus. Most MRSA strains are also resistant to multiple drugs. MRSA are more commonly found in hospital than in community. However, incidence of community-acquired MRSA infection has been emerging. MRSA strains resistant to all clinically useful drugs (except the glycopeptides vancomycin and teicoplanin) have been isolate in clinical samples.

27 MRSA Furthermore, it has been demonstrated that some enterococci, which are resistant to vancomycin resistance, have plasmids which confers vancomycin resistance. These plasmids can be transferred to Staph. aureus in the laboratory. It has been suggested that this genetic transfer of vancomycin resistance could occur naturally.

28 Streptococcus Gram positive cocci in chain Haemolysis Alpha partial haemolysis Beta complete haemolysis Gamma no haemolysis Lancefield serological groups of beta-hemolytic streptococci 20 groups A to H, K to V

29 Streptococcus pyogenes (Group A Streptococci)

30 Streptococcus pyogenes The fleshing-eating bacteria can put you on a diet FAST!!

31

32 Strep. pyogenesis Group A streptococci (GAS) pyogensis, implies pyogenic Pharyngitis Scarlet fever Respiratory infection Skin and soft tissue infections Necrotizing fasciitis Endocarditis Meningitis Arthritis Pueperal sepsis (also know as childbed or childbirth fever)

33 Strep. agalactiae Gram positive in chain Group B streptococci (GBS) Neonatal infection (Sepsis and Meningitis) Association between colonization of maternal genital tract and neonatal infection

34 Strep. pneumoniae Also know as pneumococci Gram positive diplococci Community-acquired pneumonia Otitis media Sinusitis Meningitis Endocarditis

35 Enterococci Gram postive cocci in chain Lancefield Group D Normal flora in GI tract Opportunistic pathogen In elderly patients with underlying diseases In immunocompromised host Nosocomial UTIs Peritonitis Intra-abdominal abscess Biliary tract infection Surgical site infection Endocarditis (20% of bacterial endocarditis)

36 Gram positive rods Bacillus anthracis Clostridium tetani Corynebacterium diphtheriae Not Gram Stain

37 Bacillus Gram positive rods Aerobic endospore-forming Most species are not pathogenic Pathogenic species include: Bacillus anthracis causes anthrax Bacillus cereus causes food poisoning

38 Clostridium Gram positive rods Anaerobic endospore-forming Examples of pathogenic species: Clost. botulinum Causes botulism Produce powerful toxin Toxin in biomedical and cosmetic applications i.e. BOTOX Clost. difficile Causes antibiotic associated colitis Clost. perfingens Causes deep wound infection Clost. tetani Causes tetanus

39 Clostridium difficile toxins Antibiotic-associated diarrhoea and colitis Toxin A (Enterotoxin) Toxin B (Cytotoxin)

40 Food-borne botulism Clostridium botulinum and botulism Symptoms usually develop within 24 hours of consuming contaminated food although in some cases they may not develop for several days Typical signs and symptoms include weakness, fatigue, dryness of the mouth and there may be difficulty swallowing As the neurotoxin continues to exert its poisonous effects on the nervous system, speech and vision begin to suffer and ultimately paralysis sets in Death typically occurs from respiratory failure

41 Botulinum toxin Botulinum toxin is produced by pathogenic strains of Clostridium botulinum Botulinum toxin is one of the most potent human toxins known A biological weapon? A therapeutic agent A cosmetic agent

42 Therapeutic use of botulinum toxin Botulinum toxin causes persistent muscle relaxation Botulinum toxin is licensed for medical use and has been marketed worldwide for over 10 years (as Botox) The therapeutic exploitation is based on the fact that botox acts as a specific muscle relaxant It is used as the preferred treatment for a variety of conditions that involve involuntary muscle spasms

43 Cosmetic use of Botox

44 Tetanus Sir Charles Bell's portrait of a wounded soldier suffering from tetanus (circa 1821)

45 Tetanus

46 Botulinum toxin vs tetanus toxin The tetanus toxin and botulinum toxin produce dramatically different effects in the host. Botulinum toxin Tetanus toxin persistent muscle relaxation persistent muscle contraction

47 Listeria Pathogenic species: Listeria monocytogenes Causes diseases in neonates Sepsis Meningitis Milk products are the most common sources of infection

48 Corynebacterium Most species are normal flora of: Skin Nasopharynx Pathogenic species: Toxigenic stains of C. diptheriae

49 Corynebacterium diphtheriae Chinese characters

50 Diphtheria Toxin Toxigenic strain of the bacteria can produce a toxin which can cause diptheria. 100 ng/kg is a lethal dose for most human. A toxin molecule can kill one cell. About 7% of people who contract diptheria die from it.

51 Bacteriophage infecting C. diphtheriae

52 Diphtheria a membrane, namely pseudomembrane, grows around the inside of the throat Difficulty in swallowing, breathlessness and suffocation

53 Pseudomembrane Greyish pseudomembrane

54 Diphtheria Patients shows the typical Bull-neck appearance.

55 Gram negative cocci Neisseria gonorrhoeae Neisseria meningitidis

56 Neisseria gonorrhoeae Causative agent of gonorrhea a sexually transmitted disease (STD) Symptomatic or asymptomatic localized infections In males: Causes acute urethritis and purulent urethal discharge 10% untreated cases have ascending infection gonococcal epididymitis, prostatitis and periurethal abscess In females: Primary infection in endocervix Urethal infection Vaginal discharge Abnormal bleeding from vagina 10% to 20% ascending infection; pelvic inflammation disease (PID) Oropharygneal gonococcal infection Anorectal gonococcal infection Conjuctivatis

57 Neisseria meningitidis Can be found in pharynx Causes meningitis and bacteremia Mortality rate up to 30%

58 Gram negative rods Straight E.coli Samonella spp. Shigella spp. Simple Curved Vibrio cholerae Vibrio parahaemolytics Not Gram Stain Spiral Treponema pallidum Borrelia burgdorferi Not Gram Stain

59 E. coli Normal flora in intestines Most common causative agents of UTIs Wound infection Biliary tract infection Bacteremia Some strains cause diarrhoea or bloody diarrhoea

60

61 Progression of E coli O157:H7 infections in children HUS - hemolytic uremic syndrome

62 Virulence factors of E.coli O157:H7 Verotoxins (Shiga like toxins) Adherence factors Other virulence factors

63 Some pathogenic types of E. coli Enterohemorrhagic E. coli (EHEC) O157:H7 Produces Shiga toxin Causes hemorrhagic colitis, bloody diarrhea Causes hemolytic uremic syndrome and kidney failure Enteroinvasive E. coli (EIEC) Invades cells of the colon Watery and occasionally bloody diarrhea (similar to Shigella) Enteropathogenic E. coli (EPEC) Infantile diarrhea Does not produce enterotoxin or Shiga toxin Not invasive Enterotoxigenic E. coli (ETEC) Causes traveler s diarrhea Causes watery, nonbloody diarrhea of considerable volume (little or no fever)

64 Salmonella Only two species (Clin. Microbiology Manual, 2003): Salmonella enterica Salmonella bongori However, there are about 2500 serotypes. Examples: Salmonella Typhi (serotype is not italicized) Salmonella Paratyphi A Salmonella Paratyphi B Salmonella Paratyphi C Salmonella Typhimurium

65 Typhoid fever A serious bloodstream infection Sustained high fever Headache Without diarrhea Humans are the only reservoir Healthy carrier (e.g. Typhoid May) Transmit through faecal-oral route Serotypes Paratyphi A, B and C cause similar syndrome to typhoid fever.

66 Nontyphoidal Salmonella Cause intestinal infection Diarrhea Fever Abdominal cramps Can cause UTIs and bacteremia but less common Salmonella is ubiquitous in animal populations Human illness is usually linked to foods of animal origin (e.g. eggs)

67 Shigella Four species: Shigella dysenteriae Shigella flexneri Shigella boydii Shigella sonnei Causes bloody diarrhea (dysentery) and nonbloody diarrhea Diarrhea Fever Abdominal cramps Progress to classical dysentery with scant stools containing blood, mucus and pus Complication: Hemolytic uremic syndrome (HUS)

68 Vibrio Diarrhea Vibrio cholerae Vibrio parahemolyticus Wound infection and bacteremia Vibrio vulnificus Vibrio damsela

69 Haemophilus Gram negative coccobacilli Examples of species associated with human diseases: H. influenzae One of the leading causes of meningitis in children Pneumonia Bacteremia Epiglottitis H. aegyticus Acute purulent and contagious conjunctivitis H. ducreyi Genital ulcers

70 Treponema pallidum Spirochaetes Causative agents of syphilis, a sexually transmitted disease (STD) Primary (average 21 days) Local lesions Chancre Regional lymphadenopathy Secondary (6 wk 6 mo postinfection) Generalized lymphadenopathy fever, CNS involvement, Asymptomatic Latent Asymptomatic Tertiary Tissue destruction of organs CNS involement symptomatic Optic atrophy Paresis

71 Mycoplasma Mycoplasma pneumoniae Lack of cell wall Resistant to antibiotics which act on cell wall synthesis Causes the upper and lower respiratory tracts. Cough, fever, and headache may persist for several weeks. It affects mainly school-aged children Infection occurs worldwide and is more prevalent in colder months

72 Mycobacterium tuberculosis (MTB) Causative agent of tuberculosis Characteristics: Acid-fast bacilli Slow growing (when compared with other bacteria such E.coli) Airborne affects the lower respiratory system chronic cough low-grade fever night sweats weight loss

73 Pathogenesis MTB enter the alveoli by airborne transmission. resist destruction by alveolar macrophages and multiply forming the primary lesion or tubercle spread to regional lymph nodes Tissue destruction results from cellmediated hypersensitivity.

74 Intracellular Bacteria Chlamydiae Rickettsiae

75 Chlamydiae Obligate intracellular bacteria Have outer and inner membrane but no cell wall (peptidoglycan) Lack several metabolic and biosynthetic pathways Depend on the host cell for intermediates, including ATP

76 Medical important species C. psittaci Causes psittacosis (a zoonosis) Lower respiratory tract infection Fever Headache Muscle aches Cough An occupational health hazard of poultry workers Natural habitat: Birds C. pneumomiae Causes acute respiratory infection Natural habitat: Human C. trachomatis Conjunctivitis Genital tract infection e.g. nongonococcal urethritis Natural habitat: Human

77 Chlamydiae Chlamydiae exist as two stages: (1) infectious particles called elementary bodies (2) intracytoplasmic, reproductive forms called reticulate bodies.

78 The Chlamydia life cycle Engel J. PNAS 2004;101: by National Academy of Sciences

79 Figure 1. Transmission electron micrograph of Chlamydia pneumoniae associated with macrophages (RAW cells). A. Typical pear shaped EBs (arrows) are shown at the macrophage surface. B. Intracellular EBs display the typical pear shaped morphology and a large periplasmic space containing round electron-dense bodies (arrowheads). Scale bar = 0.5µm.

80 Rickettsiae Gram-negative bacilli Gram-negative-type cell envelope Obligate intracellular parasites Two antigenically defined groups: spotted fever group Rickettsiae rickettsii typhus group Rickettsiae prowazekii

81 Spotted fever Rickettsia rickettsii Primarily a parasite of tickes Symptoms (2 6 days after infection): Fever Headache Rash (most charasteristic feature) Mental confusion Muscle pain Rash on palms, soles, wrists and ankle Rash progressively spread to trunk in a few hours

82 Typhus Rickettsia prowazekii Transmit to humans by the body louse (louse-borne) Louse bite Contact with infectious dried louse feces Symptoms Fever Headache Rash Muscle pain Rash appears first on the trunk and then to extremities

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