Antibiotic Resistance –
and the wisdom of Jimmy Buffet
(more human folly than superbugs)
Martin Cormican, Centre for Health from Environment
Ryan Institute, National University of Ireland, Galway
Antimicrobial Resistance and Microbial Ecology Group
School of Medicine, NUI Galway
The Talk In A Tweet
The microbial world is a gene cloud
• The cloud leaks through barriers
• The genes takes new shapes
• We make resistance the winning shape
•
The Talk in In Pictures: Antibiotic
Resistance
3
One Health
•
OIE endorses the “One Health” approach as a collaborative and
all-encompassing way to address, when relevant, animal and public
health globally
People
•
Animals
PrGWS C – E. Galway
PrGWS K – N. Galway
Groundwater/Stream
Spring Well
~ 115 Houses
~ 277 Houses
PrGWS M – N.E. Galway
Spring Well
~ 354 Houses
Rural Water
Supplies
Antimicrobial Resistance:
We Are Not Always Blaming Vets
Charles Darwin
Antimicrobial-Resistance & Theory of Evolution
7
Finches
8
What is a Species ?
The Orderly World of Zoology
•
Male & Female Can Mate and Produce Fertile Offspring
•
DNA is transmitted vertically from parent to offspring
•
Gradual step-wise change
•
DNA sequences don’t wander about between species
9
What is a Species ?
The Chaotic World of Bacteria
•
Bacteria that group together as relatively similar to each other
in terms of DNA sequence compared with all other bacteria
are called a species
•
The boundary between one species & anohter is fairly
arbitrary
•
DNA is transmitted vertically from mother to daughter cell
•
But DNA sequences wander about all over the place
•
Major changes happen all the time
10
The Microbial Gene Cloud
11
The Microbial Gene Information Cloud
12
Antimicrobial Agents : Flemings Mould
•
Antimicrobial agents have always
existed in the environment e.g. soil &
water
•
Bacteria that could survive in
presence of these agents are better at
multiplying in that setting
•
Natural Selection: Environmental
Bacteria Tend to Be Antibiotic
Resistant
•
Intrinsic Resistance
13
Intrinsic Resistance
•
Pseudomonas aeruginosa
•
When Fleming discovered penicillin Pseudomonas aeruginosa
was already resistant
•
Also resistant to many other antibiotics
•
Rarely cause infection (unless already sick)
14
Why they Were Originally Susceptible
•
Little exposure to antimicrobial
agents in animal associated
bacteria
•
Commensals or pathogens
•
Little selection pressure to favor
bacteria with resistance genes
•
A rare S. aureus or E. coli with a
resistance gene has no advantage
and may have excess bagage
15
Acquired Resistance in Originally Susceptible
Bacteria
• The era of therapeutic antimicrobial use
• Intense selection pressure on bacteria of
animals /humans
• S. aureus and E. coli without the extra
baggage die
• Variants with the baggage surive multiply &
spread
16
General Biocides & Therapeutic Antimicrobial
Agents
• A useful therapeutic antimicrobial
• A) stop/kill bacteria
• B) not stop/kill host (people & animals)
• Act at specific biological targets that are
present and important in target bacteria but
absent or not important in host
17
The Class Concept
• Similar chemical compounds usually act at
the same target or targets
• e.g. all penicillins & all cephalosporins have
common chemical motif & all act on enzymes
that are important in buidling the bacterial
cell wall
18
The Class Concept
• Changes in the specific target that reduce
vulnerability to inhibition by one of them often
results in loss of vulnerability to several /many
or to all penicillins & cephalosporins
• Enzymes that inactivate one of them often
inactivate several/many or all penicillins &
cephalosporins to some degree
19
The Class Concept & Regulatory
Pharmaceutical Guff
• Licensing & Promotion of one fluoroquinolone
in animals and a different one in human
20
Acquired Antibiotic Resistance
•
Well understood, entirely predictable and possibly
inevitable consequence of antibiotic use
•
A consequence of inappropriate use and of appropriate
use
•
A consequence of use no matter who
prescribes/consumes them or for whatever purpose
•
But overuse and irrational use makes it happen faster
and for no corresponding benefit
21
Acquired Antibiotic Resistance:
No Superbugs Just Human Folly
•
•
•
We pretty know how & why it happens
We have a very good idea how to slow it down
Nationally & Globally we can not organize ourselves
to act
•
“Wicked Problem”
22
Intermission
• End of Part One
23