5. I. Introduction to basic physiology and concepts of pathogenesis
II. Bacterial cell structures
III. Growth and nutrition
IV. Antibiotic resistance-mutation and genomic
change
V. Antibiotic resistance-gene exchange

8. I. Introduction to basic physiology and concepts of pathogenesis
II. Bacterial cell structures
III. Growth and nutrition
IV. Antibiotic resistance-mutation and genomic
change
V. Antibiotic resistance-gene exchange

9. The major cellular targets of antibiotics
Peptidoglycan synthesis
Cycloserine
Vancomycin
Penicillins
Cephalosporins
Bacitracin
DNA
RNA polymerase
Rifampin
mRNA
30S
50S
Cell membrane
Polymixins
Ribosome inhibitors
Erythromycin
Chloramphenicol
Clindamycin

10. I. Introduction to basic physiology and concepts
of pathogenesis
II. Bacterial cell structures
III. Growth and nutrition
IV. Antibiotic resistance-mutation and genomic
change
V. Antibiotic resistance-gene exchange

11. Metabolism
Glycolysis
Fermentation
TCA
Cycle
Respiration

12. I. Introduction to basic physiology and concepts
of pathogenesis
II. Bacterial cell structures
III. Growth and nutrition
IV. Antibiotic resistance-mutation and genomic
change
V. Antibiotic resistance-gene exchange

13. Genomes within bacteria
Virus
Genome
Plasmid

14. I. Introduction to basic physiology and concepts
of pathogenesis
II. Bacterial cell structures
III. Growth and nutrition
IV. Antibiotic resistance-mutation and genomic
change
V. Antibiotic resistance-gene exchange

15. Genetic exchange

16. VI. Virulence-basic mechanisms of gene
regulation
VII. Virulence- mechanisms of adaptation
VIII. Emerging infections
IX. Regulation of virulence-Example of
Salmonella
X. Regulation of virulence-Example of
Neisseria gonorrhea

17. Gene regulation P P Receptor senses the environment Protein controls
gene expression P P
DNA

18. VI. Virulence-basic mechanisms of gene
regulation
VII. Virulence- mechanisms of adaptation
VIII. Emerging infections
IX. Regulation of virulence-Example of
Salmonella
X. Regulation of virulence-Example of
Neisseria gonorrhea

19. Adaptation

20. VI. Virulence-basic mechanisms of gene
regulation
VII. Virulence- mechanisms of adaptation
VIII. Emerging infections
IX. Regulation of virulence-Example of
Salmonella
X. Regulation of virulence-Example of
Neisseria gonorrhea

23. VI. Virulence-basic mechanisms of gene
regulation
VII. Virulence- mechanisms of adaptation
VIII. Emerging infections
IX. Regulation of virulence-Example of
Salmonella
X. Regulation of virulence-Example of
Neisseria gonorrhea

24. Regulation of virulence
Stomach:
Acid tolerance
Small intestine:
Invasion

25. VI. Virulence-basic mechanisms of gene
regulation
VII. Virulence- mechanisms of adaptation
VIII. Emerging infections
IX. Regulation of virulence-Example of
Salmonella
X. Regulation of virulence-Example of
Neisseria gonorrhea

26. Regulation of virulence:pilus variation

27. Fundamental concepts in bacteriology
Bacterial diversity and the microbiota
Classification (diagnosis)
Steps in pathogenesis:
Infection involves multiple steps. Focus on an early step: adherence.
A successful pathogen has adapted to survive host defenses and to cause disease.

28. Diversity of life
The number of bacterial species is vast. 1000’s of species (a very very small subset of the bacteria) comprise the human microbiota. A much smaller number of species can actually cause disease in humans.
Archea are not (yet) known to cause human disease. However, they have been discovered among the human microbiota.

29. Diversity of life

30. Most (probably all) animals harbor a complex bacterial community called the microbiota
The human microbiota is extremely complex. It spans 1000’s of species including some archea. Most of these species remain unidentified.
There are 10 times more bacterial cells than human cells in a person.
The bacterial species in an individual’s microbiota varies with age, geography and lifestyle.
The microbiota participate in organ development, digestion of food, and synthesis of vitamins. The microbiota are especially important in preventing bacterial infection. The microbiota and the immune system influence each other. Still, the impact of the microbiota on normal health is much more complex than currently appreciated.

31. The microbiota are present throughout the GI tract
The geographical distribution of the microbiota is a new area of study. Locations of particular interest: GI tract, skin, respiratory tract, vagina, penis.
Adapted from Leser and Molbak, Env. Microbiol 2009

32. Changing historical perspectives on bacteria and human health
1. Bacteria are, most importantly, agents of disease. However, some live in harmony with the host or even contribute to host well being. 2. Most bacteria are harmless. Only a few highly adapted bacteria cause disease. Probably, the bacteria normally found in a healthy host are needed to suppress disease. 3. Hosts possess enormous, highly complex bacterial communities that are essential for health. The composition and distribution of these organisms emerges from a complex homeostasis involving the bacteria, the host immune system, life style and other host and environmental factors.
4. The bacteria and the host have coevolved and continue to do so. The integration of their evolutionary histories makes them effectively inseparable.

39. A device to measure metabolism of sugars and other compounds

40. Growth on antibiotics

41. Gram stain: purple, Gram +; pink, Gram -

42. Additional methods for bacterial identification:
1. Determine the ability of bacteria to grow on a variety of chemically distinct media: the preferred growth medium can identify the organism. 2. Identify the sugars used during, and the organic products of, fermentation (only during anaerobic conditions). 3. Determine whether peroxidases or superoxide dismutatases are present; if so, the bacterium can likely perform oxidative metabolism.
5. Identify genes specific to a given pathogen.

43. Identify bacteria by genes specific for given pathogen
Analyze DNA from an infection site to determine whether pathogen-specific DNA is present.
This requires knowledge of genes unique to a given pathogen. This requires significant basic science analysis.

44. PCR can identify specific DNA sequences
Bacterial DNA `
Oligonucleotide probes

46. Diagnostic tests are only as reliable as the collection and culture methods
Be sure to avoid contamination from organisms present at the collection site.
Beware of downstream contamination (blood banks).
Be suspicious of blood drawn from indwelling central venous catheters.
Be knowledgeable about the real local pathogens. Be suspicious of infections by organisms not known to be in the environment.
Be meticulous about your own sanitation (hands, equipment, vaccination). Stay home when you are sick.

47. EXPOSURE
to pathogens
ADHERENCE
to skin or mucosa
INVASION
though epithelium
COLONIZATION
and GROWTH production of
virulence factors
SPREAD
TOXICITY
DISEASE

48. Steps in B. pertussis pathogenesis
There can be many consequences to adhesion and invasion!

49. Steps in pathogenesis How might a bacterium cause significant disease
WITHOUT invading or even adhering? Is this even possible?

50. Barriers to entry and adherence

51. Examples of pathogen adherence
V. cholera, w/o capsule, rabbit brush boarder
EPEC (E. coli), w/capsule, calf brush boarder

52. Direct consequences of pathogen adherence
Activation of the immune system: adaptive and innate immunity
Adapted from Bhavsar et al. Nature 2007

53. Direct consequences of pathogen adherence
Uptake into a specialized, double membrane intracellular compartment
Adapted from Bhavsar et al. Nature 2007

54. Direct consequences of pathogen adherence
Cytoskeletal rearrangement, formation of a specialized lesion and entry into the host cell
Adapted from Bhavsar et al. Nature 2007

55. Direct consequences of pathogen adherence
Cytoskeletal rearrangement, formation of a specialized lesion and some degree of entry into the host cell
Adapted from Bhavsar et al. Nature 2007

56. Preferred niches of certain pathogens

57. Normal flora
These are commensal interactions!

58. Normal flora in the wrong place
What happens when a commensal bacterium enters a location in the body that it does not normally occupy (as can happen during surgery)?

59. Fundamental concepts in bacteriology
Bacterial diversity and the microbiota
Classification (diagnosis)
Steps in pathogenesis:
Infection involves multiple steps. Focus on an early step: adherence.
A successful pathogen has adapted to survive host defenses and to cause disease.