麻省理工大学课件：系统微生物学17-微生物与宿主的相互作用(PPT)
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• Common mechanisms
1. Lack structure drug targets 2. May be impermeable to drug 3. Organism may be able to modify drug to an inactive
form 4. Organism may modify the target itself 5. Organism may develop a new pathway 6. Organism may be able to pump out the drug
http://www.cdc.gov/ncidod/dhqp/healthDis.html
Changing patterns for HAIs
• 1950s to 1960s gram positive bacteria
were a major problem (Streptococcus
Enterococcus faecalis
Gram-negative Gram-positive Gram-positive/acid-fast
Streptococcus pneumoniae Mycobacterium tuberculosis Haemophilus ducreyi Salmonella typhi
R factors
• Most drug resistant bacteria isolated from patients contain drug resistance genes on plasmids
• Many of these plasmids encode enzymes that inactivate drugs
Methicillin-resistant
Staphylococcus aureus N315
Image removed due to copyright restrictions.
Hiramatsu et al. Trends Microbiol 9:486, 2001
Terminology
Indigenous microbiota
• Microorganisms that inhabit body sites in which surfaces and cavities are open to the environment
• Skin, oral cavity, upper respiratory tract,
pyogenes and Staphylococcus aureus)
• 1970s and 1980s gram negative bacteria became a major problem (E. coli and Pseudomonas spp.)
• Currently, gram positive bacteria are again emerging as a major problem (S. aureus and Enterococcus spp.)
• Healthcare-associated infections (HAIs) are infections that patients acquire during the course of receiving treatment for other conditions
• In hospitals alone, HAIs account for an estimated 2 million infections, 90,000 deaths, and $4.5 billion in excess health care costs annually
• Multi-drug resistance plasmids predate medical use of antibiotics
• Widespread emergence of multi-drug resistance
Resistance to all known drugs…
Acinetobacter sp.
gastrointestinal (GI) tract, and vagina
• Each habitat can be considered a separate ecosystem
Haemophilus influenzae Neisseria gonorrhoeae
Pseudomonas aeruginosa
Salmonella sp.
Shigella dysenteriae
Shigella sp.
Other gram-negative rods
Staphylococcus aureus
Microbe-host interactions
Nov 15, 2006
Ch. 21
Science 307:1915-20, 2005.
Baidu Nhomakorabea
Antimicrobial drug resistance
• Acquired ability to resist effects of a chemotherapeutic to which it is normally susceptible
• Normal microbial “flora” or “microflora”
– Better term is microbiota – Commensal (at the same table)
• Pathogen
– Infection versus disease
• Virulence • Opportunistic pathogen
1950 1960 1970 1980 1990 2000 2010
Figure by MIT OCW.
• Methicillin-
resistant
Staphylococcus
aureus (MRSA)
• Vancomycinresistant Enterococcus (VRE)
Healthcare-associated infections
1. Lack structure drug targets 2. May be impermeable to drug 3. Organism may be able to modify drug to an inactive
form 4. Organism may modify the target itself 5. Organism may develop a new pathway 6. Organism may be able to pump out the drug
http://www.cdc.gov/ncidod/dhqp/healthDis.html
Changing patterns for HAIs
• 1950s to 1960s gram positive bacteria
were a major problem (Streptococcus
Enterococcus faecalis
Gram-negative Gram-positive Gram-positive/acid-fast
Streptococcus pneumoniae Mycobacterium tuberculosis Haemophilus ducreyi Salmonella typhi
R factors
• Most drug resistant bacteria isolated from patients contain drug resistance genes on plasmids
• Many of these plasmids encode enzymes that inactivate drugs
Methicillin-resistant
Staphylococcus aureus N315
Image removed due to copyright restrictions.
Hiramatsu et al. Trends Microbiol 9:486, 2001
Terminology
Indigenous microbiota
• Microorganisms that inhabit body sites in which surfaces and cavities are open to the environment
• Skin, oral cavity, upper respiratory tract,
pyogenes and Staphylococcus aureus)
• 1970s and 1980s gram negative bacteria became a major problem (E. coli and Pseudomonas spp.)
• Currently, gram positive bacteria are again emerging as a major problem (S. aureus and Enterococcus spp.)
• Healthcare-associated infections (HAIs) are infections that patients acquire during the course of receiving treatment for other conditions
• In hospitals alone, HAIs account for an estimated 2 million infections, 90,000 deaths, and $4.5 billion in excess health care costs annually
• Multi-drug resistance plasmids predate medical use of antibiotics
• Widespread emergence of multi-drug resistance
Resistance to all known drugs…
Acinetobacter sp.
gastrointestinal (GI) tract, and vagina
• Each habitat can be considered a separate ecosystem
Haemophilus influenzae Neisseria gonorrhoeae
Pseudomonas aeruginosa
Salmonella sp.
Shigella dysenteriae
Shigella sp.
Other gram-negative rods
Staphylococcus aureus
Microbe-host interactions
Nov 15, 2006
Ch. 21
Science 307:1915-20, 2005.
Baidu Nhomakorabea
Antimicrobial drug resistance
• Acquired ability to resist effects of a chemotherapeutic to which it is normally susceptible
• Normal microbial “flora” or “microflora”
– Better term is microbiota – Commensal (at the same table)
• Pathogen
– Infection versus disease
• Virulence • Opportunistic pathogen
1950 1960 1970 1980 1990 2000 2010
Figure by MIT OCW.
• Methicillin-
resistant
Staphylococcus
aureus (MRSA)
• Vancomycinresistant Enterococcus (VRE)
Healthcare-associated infections