Commensal, opportunistic & pathogenic bacteria

Professor Mark Pallen

Outline
Definitions Interactions between humans and bacteria Changes in normal flora Benefits of normal flora Why care about the normal flora? Normal flora
Throat and mouth Skin and nose Adult female genital tract Large bowel Harmful effects of gut flora Harmful alterations in gut flora

Definitions
Pathogen
an organism that can cause infection in individuals with normal host defences, e.g., Salmonella enteritidis, Vibrio cholerae

Commensal
an organism that is found normally on those parts of the body that are exposed to, or communicate with, the external environment, eg. Bacteroides fragilis, Staphylococcus epidermidis; the 'normal flora'

Opportunistic pathogen ('opportunist')

an organism that can cause infection in individuals with abnormal host defences. Commensals may be opportunistic pathogens.

Microbes and humans

Very few microbes are always pathogenic

Many microbes are potentially pathogenic

Most microbes are never pathogenic

Microbes and humans

Disease can come about in several overlapping ways
1. Some bacteria are entirely adapted to the pathogenic way of life in humans. They are never part of the normal flora but may cause subclinical infection, e.g. M . tuberculosis 2. Some bacteria which are part of the normal flora acquire extra virulence factors making them pathogenic, e.g. E. coli 3. Some bacteria which are part of the normal flora can cause disease if they gain access to deep tissues by trauma, surgery, lines, e.g. S. epidermidis 4. In immunocompromised patients many free-living bacteria and components of the normal flora can cause disease, especially if introduced into deep tissues, e.g. Acinetobacter

How do we know that a given pathogen causes a specific disease? Koch's postulates
the pathogen must be present in every case of the disease the pathogen must be isolated from the diseased host & grown in pure culture the specific disease must be reproduced when a pure culture of the pathogen is inoculated into a healthy susceptible host the pathogen must be recoverable from the experimentally infected host

The iceberg concept of infectious disease

poliomyelitis in a child 0.1-1% of infections are clinically apparent

classical clinical disease less severe disease

rubella 50% of infections are clinically apparent

Spectrum of virulence

asymptomatic infection

rabies 100% of infections are clinically apparent

How do we know that a given pathogen causes a specific disease?

Diagnosis and effective treatment of infection depends not just on isolating an organism, but in establishing a plausible link between the laboratory findings, recognised syndromes and the patient's clinical condition

Recognised syndromes e.g. septicaemia, endocarditis, osteomyelitis meningitis, UTI, pneumonia pharyngitis

potential pathogen isolated from or detected in clinical samples

patient's clinical condition

Microbes and humans

Evidence for a potential pathogen being clinical significant (particularly for bacteria)
Isolated in abundance Isolated in pure culture Isolated on more than one occasion Isolated from deep tissues Evidence of local inflammation Evidence of immune response to pathogen Fits with clinical picture

The Normal Flora

A New Year Greeting
After an article by Mary J. Marples in Scientific American, January, 1969 On this day tradition allots to taking stock of our lives, my greetings to all of you, Yeasts, Bacteria, Viruses, Aerobics and Anaerobics: A Very Happy New Year to all for whom my ectoderm is as Middle-Earth to me. For creatures your size I offer a free choice of habitat, so settle yourselves in the zone that suits you best, in the pools of my pores or the tropical forests of arm-pit and crotch, in the deserts of my fore-arms, or the cool woods of my scalp. Build colonies: I will supply adequate warmth and moisture, the sebum and lipids you need, on condition you never do me annoy with your presence, but behave as good guests should, not rioting into acne or athlete's-foot or a boil..

W.H. Auden

The Normal Flora

Our bodies are like mobile warmblooded coral reefs, rich in microbial biodiversity and home to vast numbers of bacterial cells
there are more bacterial cells (1014) associated with the human body than there are human ones (only 1013)!

composition of normal flora varies from individual to individual

some bacterial species carried only transiently most fairly permanent difficult to alter composition of the normal flora ofgut in a healthy individual

Changes in normal flora

with changes in hormal physiology and development
female genital tract and lactobacilli

when antibiotics select for a 'resistant flora

Candida overgrowth in mouth, vagina Clostridium difficile (antibiotic-associated colitis)

new organisms may be acquired

neonate from maternal genital tract during birth Gram-negative colonisation of gut and URT in hospitalised patients Cross-infection with C. difficile, MRSA, VRE etc

Why care about the normal flora?

it may be good for you! colonization resistance:
competition for space and nutrients with pathogens

release of bacteriocins and colicins (antibacterial substances) to prevent pathogen growth vitamin K production in gut continued antigenic stimulation from commensals
cross-reacting protective immunity against pathogens commensal neisseriaceae and Neisseria meningitidis

Why care about the normal flora?

commensal bacteria may cause disease at their site of carriage or nearby, e.g.
Streptococcus mutans (mouth)
causes dental caries

Streptococcus pneumoniae (upper airways)

causes otitis media, sinusitis

Some members of the normal flora can become pathogenic if they acquire additional virulence factors (e.g. E. coli) or are introduced into normally sterile sites (e. g. Staphylococcus aureus)

Why care about the normal flora?

Normal flora as contaminants
To allow interpretation of
Gram stains on clinical samples Culture results

Skin flora in blood cultures

BUT coagulase-negative staphylococci can be pathogens in device-associated sepsis, so can be hard to interpret

Perineal flora in urine

Take an MSU! Mixed culture=contamination

Throat flora in sputum

Need to assess whether
Heavy pure growth Obtained repeatedly Fits clinical picture

The normal flora

mouth and throat
saliva has approx. 108 bacteria/ml 'viridans streptococci'
Strep. mutans, Strep. mitior, Strep. salivarius

Corynebacterium spp.
inc. C. diphtheriae toxigenic and non-toxigenic strains

Neisseria spp.
N. lactamica, N. flavescens, N. meningitidis

Haemophilus influenzae Streptococcus pneumoniae

Spirochaetes Bacteroides melaninogenicus Fusobacteria anaerobic cocci Actinomyces spp.

The normal flora

skin & nose
Staphylococcus aureus Staphylococcus epidermidis diphtheroids

The normal flora

adult female genital tract
Lactobacilli Diphtheroids Staphylococcus epidermidis Streptococci enterobacteriaceae

The normal flora

large bowel Density
Upper: Medium 108 - 1010/g Lower: High >1010/g

Organisms
Bacteroides spp. Enterobacteriaceae, esp E. coli Enterococci Clostridium spp. Candida spp.

Harmful effects of gut bacteria

escape of normal flora to abnormal sites
perforated appendix leads to peritonitis with Bacteroides spp. and facultative aerobes inc. E. coli

cholecystitis and cholangitis

often mixed infection, E. coli predominant, also including enterococci

urinary tract infection

most frequent organism in normal urinary tract is E. coli

vaginal candiosis

Harmful effects of alterations in normal gut flora

antibiotic use
leads to

Treatment
stop precipitating antibiotic give oral metronidazole or vancomycin recovery requires reestablishment of normal flora
? probiotics

sensitive gut flora killed

leads to

overgrowth with resistant flora inc. Clostridium difficile

leads to

C. difficile toxin production

leads to

Diarrhoea, pseudomembraneous colitis

Summary
Definitions Changes in normal flora Benefits of normal flora Why care about the normal flora? Normal flora
Throat and mouth Skin and nose Adult female genital tract Large bowel Harmful effects of gut flora Harmful alterations in gut flora