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Bacteriology of Humans
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For the Wilson clan – Andrew, Anne, Caroline, Edie, Fionn, Joan, Liz, Pippa, and Sarah
– a rare example of a complex community governed only by positive interactions.
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Bacteriology of
Humans
An Ecological Perspective
Michael Wilson
University College London
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© 2008 by Blackwell Publishing Ltd
BLACKWELL PUBLISHING
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1 2008
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CONTENTS
Preface, ix 1.5 The epithelium – site of host–microbe
interactions, 37
Abbreviations of genera, xi 1.5.1 Structure of epithelia, 38
1.5.2 The epithelium as an excluder of
1 THE HUMAN–MICROBE SYMBIOSIS, 1 microbes, 41
1.1 Overview of the nature and distribution of 1.5.3 Mucus and mucins, 41
the microbial communities inhabiting 1.5.4 Innate and acquired immune responses at
humans, 1 the mucosal surface, 46
1.1.1 Difficulties encountered in determining 1.6 Further reading, 53
the composition of a microbial 1.6.1 Books, 53
community, 2 1.6.2 Reviews and papers, 53
1.1.2 Structural aspects of microbial
communities, 5 2 THE INDIGENOUS MICROBIOTA OF
1.1.2.1 Microcolonies, 5 THE SKIN, 56
1.1.2.2 Intracellular colonization, 5 2.1 Anatomy and physiology of human skin, 56
1.1.2.3 Biofilms, 6 2.2 Cutaneous antimicrobial defense systems, 56
1.1.3 Communication in microbial 2.2.1 Innate defense systems, 58
communities, 8 2.2.2 Acquired immune defense systems, 60
1.2 Environmental determinants that affect the 2.3 Environmental determinants operating at
distribution and composition of microbial different skin regions, 61
communities, 13 2.4 The indigenous microbiota of the skin, 67
1.2.1 Nutritional determinants, 14 2.4.1 Members of the cutaneous microbiota, 67
1.2.2 Physicochemical determinants, 18 2.4.1.1 Corynebacteriumspp., 67
1.2.3 Mechanical determinants, 22 2.4.1.2 Propionibacteriumspp., 70
1.2.4 Biological determinants, 23 2.4.1.3 Staphylococcusspp., 71
1.3 Host characteristics that affect the indigenous 2.4.1.4 Micrococcusspp., 73
microbiota, 27 2.4.1.5 Malasseziaspp., 75
1.3.1 Age, 28 2.4.1.6 Acinetobacterspp., 76
1.3.2 Host genotype, 29 2.4.1.7 Brevibacteriumspp., 78
1.3.3 Gender, 29 2.4.1.8 Dermabacter hominis, 79
1.4 Techniques used to characterize the microbial 2.4.1.9 Methylobacteriumspp., 79
communities inhabiting humans, 31 2.4.2 Community composition at different sites,
1.4.1 Microscopy, 31 80
1.4.2 Culture-dependent approaches, 33 2.4.3 Culture-independent studies of the
1.4.3 Culture-independent, molecular cutaneous microbiota, 86
approaches, 35 2.4.4 Interactions among members of the
1.4.4 Functional analysis of microbial cutaneous microbiota, 88
communities, 37 2.5 Overview of the cutaneous microbiota, 90
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2.6 Sources of data used to compile figures , 92 4.4.1.1 Streptococcusspp., 123
2.7 Further reading, 92 4.4.1.1.1 Strep. pyogenes, 124
2.7.1 Books, 92 4.4.1.1.2 Strep. pneumoniae, 126
2.7.2 Reviews and papers, 92 4.4.1.1.3 Viridans group
streptococci, 128
3 THE INDIGENOUS MICROBIOTA OF 4.4.1.2 Neisseriaspp., 128
THE EYE, 95 4.4.1.2.1 N. meningitidis, 129
3.1 Anatomy and physiology of the eye, 95 4.4.1.2.2 Other Neisseriaspp.,
3.2 Antimicrobial defense systems of the eye, 97 131
3.3 Environmental determinants on the conjunctival 4.4.1.3 Haemophilusspp., 131
surface, 99 4.4.1.3.1 H. influenzae, 132
3.4 The indigenous microbiota of the eye, 103 4.4.1.3.2 Other Haemophilusspp.,
3.4.1 Members of the ocular microbiota, 103 134
3.4.2 Composition of the ocular microbiota, 104 4.4.1.4 Moraxella catarrhalis, 135
3.4.3 Interactions among members of the ocular 4.4.1.5 Staphylococci, 136
microbiota, 107 4.4.1.5.1 Staph. aureus, 136
3.5 Overview of the ocular microbiota, 111 4.4.1.5.2 CNS, 138
3.6 Sources of data used to compile figures, 111 4.4.1.6 Mollicutes, 139
3.7 Further reading, 111 4.4.1.7 Kingella kingae, 140
4.4.2 Community composition at the various
4 THE INDIGENOUS MICROBIOTA OF sites within the respiratory tract, 140
THE RESPIRATORY TRACT, 113 4.4.2.1 Nasal vestibule, 142
4.1 Anatomy and physiology of the respiratory 4.4.2.2 Nasal cavity, 143
tract, 113 4.4.2.3 Nasopharynx, 146
4.1.1 Nose, 113 4.4.2.4 Oropharynx, 146
4.1.2 Pharynx, 114 4.4.2.5 Lower respiratory tract, 151
4.1.3 Larynx, 114 4.4.3 Interactions among members of the
4.1.4 Trachea, 114 respiratory microbiota, 152
4.1.5 Bronchi and bronchioles, 114 4.5 Overview of the respiratory microbiota, 152
4.1.6 Alveolus, 115 4.6 Sources of data used to compile figures, 155
4.2 Antimicrobial defense systems of the respiratory 4.7 Further reading, 157
tract, 117
4.2.1 Nasal cavity, 117 5 THE INDIGENOUS MICROBIOTA
4.2.2 Other regions of the conducting OF THE URINARY SYSTEM OF
portion, 119 FEMALES, 159
4.2.3 Respiratory portion, 119 5.1 Anatomy and physiology of the urinary system of
4.3 Environmental determinants within the females, 159
respiratory tract, 119 5.2 Antimicrobial defenses of the female urinary
4.3.1 Atmospheric composition, 119 system, 160
4.3.2 pH, 120 5.3 Environmental determinants within the female
4.3.3 Nutrients, 120 urethra, 161
4.3.3.1 Composition of nasal fluid, ASL, 5.4 The indigenous microbiota of the female urethra,
and alveolar lining fluid, 120 162
4.3.3.2 Contribution of microbial 5.4.1 Members of the urethral microbiota, 163
residents of the respiratory tract to 5.4.2 Community composition in the female
nutrient availability, 122 urethra, 164
4.4 Indigenous microbiota of the respiratory 5.5 Overview of the microbiota of the urinary tract of
tract, 123 females, 167
4.4.1 Members of the respiratory microbiota, 5.6 Sources of data used to compile figures, 168
123 5.7 Further reading, 168
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6 THE INDIGENOUS MICROBIOTA OF 6.5 Overview of the microbiota of the female
THE REPRODUCTIVE SYSTEM OF reproductive system, 202
FEMALES, 170 6.6 Sources of data used to compile figures, 202
6.1 Anatomy and physiology of the female 6.7 Further reading, 204
reproductive system, 170 6.7.1 Books, 204
6.2 Antimicrobial defense systems of the female 6.7.2 Reviews and papers, 204
reproductive system, 172
6.2.1 Innate defense systems, 173 7 THE INDIGENOUS MICROBIOTA OF
6.2.2 Acquired immune defense systems, 174 THE URINARY AND REPRODUCTIVE
6.3 Environmental determinants at different regions SYSTEMS OF MALES, 207
of the reproductive system, 176 7.1 Anatomy and physiology, 207
6.3.1 Vagina, 176 7.2 Antimicrobial defenses of the male urinary and
6.3.2 Cervix, 179 reproductive systems, 207
6.3.3 Vulva, 179 7.3 Environmental determinants within the male
6.3.4 Contribution of the indigenous microbiota urinary and reproductive systems, 210
to nutrient supply within the reproductive 7.4 The indigenous microbiota of the male urinary
system, 179 and reproductive systems, 211
6.4 The indigenous microbiota of the female 7.4.1 Members of the microbiota, 211
reproductive system, 181 7.4.2 Microbiota of the male urethra, 212
6.4.1 Members of the microbiota, 181 7.4.3 Microbiota of the glans penis, 216
6.4.1.1 Lactobacillusspp., 181 7.4.4 Microbiota of the prostate, 218
6.4.1.2 Gardnerella vaginalis, 184 7.5 Overview of the microbiota of the male urinary
6.4.1.3 Candida albicans, 184 and reproductive systems, 218
6.4.1.4 Streptococcus agalactiae(Group B 7.6 Sources of data used to compile figures, 219
streptococcus), 186 7.7 Further reading, 220
6.4.1.5 Mycoplasma hominis, 186
6.4.1.6 Ureaplasma urealyticum, 186 8 THE INDIGENOUS MICROBIOTA OF
6.4.1.7 Atopobium vaginae, 187 THE ORAL CAVITY, 222
6.4.1.8 Mobiluncusspp., 187 8.1 Anatomy and physiology of the oral cavity, 222
6.4.2 Community composition at different sites 8.2 Antimicrobial defense systems of the oral cavity,
within the female reproductive system, 187 225
6.4.2.1 Vagina, 187 8.3 Environmental determinants at the various sites
6.4.2.1.1 Post-menarcheal/pre- within the oral cavity, 228
menopausal females, 8.3.1 Mechanical determinants, 228
187 8.3.2 Nutritional determinants, 228
6.4.2.1.2 Pre-menarcheal girls, 8.3.3 Physicochemical determinants, 231
191 8.4 The indigenous microbiota of the oral cavity, 232
6.4.2.1.3 Post-menopausal 8.4.1 Members of the oral microbiota, 235
women, 192 8.4.1.1 Oral streptococci and related
6.4.2.1.4 Vaginal microbiota Gram-positive cocci, 235
during pregnancy, 193 8.4.1.2 Gemellaspp., 235
6.4.2.2 Cervix, 193 8.4.1.3 Actinomycesspp., 236
6.4.2.2.1 Post-menarcheal/pre- 8.4.1.4 Rothia dentocariosa, 237
menopausal females, 8.4.1.5 Veillonellaspp., 237
197 8.4.1.6 Anaerobic and microaerophilic
6.4.2.2.2 Cervical microbiota Gram-negative rods, 237
during pregnancy, 197 8.4.1.6.1 Fusobacteriumspp., 237
6.4.2.3 Vulva, 199 8.4.1.6.2 Porphyromonasspp.,
6.4.3 Interactions between organisms colonizing 238
the female reproductive system, 200 8.4.1.6.3 Prevotellaspp., 239
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8.4.1.6.4 Spirochaetes, 239 9.4.1.2 Eubacterium, 283
8.4.1.6.5 Other anaerobic 9.4.1.3 Roseburia, 284
species, 239 9.4.1.4 Clostridium, 284
8.4.1.7 Facultatively anaerobic Gram- 9.4.1.5 Bifidobacterium, 284
negative bacilli, 240 9.4.1.6 Enterococcus, 285
8.4.1.8 Mycoplasmaspp., 240 9.4.1.7 Helicobacter pylori, 286
8.4.1.9 Megasphaeraspp., 241 9.4.1.8 Enterobacteriaceae, 286
8.4.2 Community composition at different 9.4.1.9 Ruminococcus, 287
sites, 241 9.4.1.10 Methanogenic organisms, 287
8.4.2.1 Supragingival plaque, 241 9.4.1.11 Desulfovibrio, 287
8.4.2.2 Gingival crevice, 253 9.4.1.12 Acidaminococcus, 288
8.4.2.3 Tongue, 256 9.4.1.13 Faecalibacterium prausnitzii, 288
8.4.2.4 Other mucosal surfaces, 257 9.4.2 Community composition in different
8.5 Overview of the oral microbiota, 261 regions of the intestinal tract, 288
8.6 Sources of data used to compile figures, 263 9.4.2.1 Esophagus, 288
8.7 Further reading, 264 9.4.2.2 Stomach, 289
8.7.1 Books, 264 9.4.2.3 Small intestine, 295
8.7.2 Reviews and papers, 264 9.4.2.3.1 Duodenum, 295
9.4.2.3.2 Jejunum, 295
9 THE INDIGENOUS MICROBIOTA OF 9.4.2.3.3 Ileum, 301
THE GASTROINTESTINAL TRACT, 266 9.4.2.4 Large intestine, 302
9.1 Anatomy and physiology of the gastrointestinal 9.4.2.4.1 Cecum, 304
tract, 267 9.4.2.4.2 Colon, 306
9.2 Antimicrobial defense systems of the 9.4.2.4.3 Rectum, 316
gastrointestinal tract, 272 9.4.3 Microbial interactions in the
9.2.1 Innate defense systems, 272 gastrointestinal tract, 317
9.2.2 Acquired immune defense system, 275 9.5 Overview of the indigenous microbiota of the
9.3 Environmental determinants within different gastrointestinal tract, 320
regions of the gastrointestinal tract, 276 9.6 Sources of data used to compile figures, 320
9.3.1 Esophagus, 276 9.7 Further reading, 322
9.3.2 Stomach, 277 9.7.1 Books, 322
9.3.3 Small intestine, 277 9.7.2 Reviews and papers, 322
9.3.4 Large intestine, 278
9.4 The indigenous microbiota of the gastrointestinal 10 THE FUTURE, 327
tract, 280 10.1 Further reading, 329
9.4.1 Members of the intestinal microbiota, 282
9.4.1.1 Bacteroides, 282 Index, 331
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PREFACE
More than 50 years ago, Dylan’s The Times they Are further and should turn immediately to the table of
A-Changingreverberated around the planet and, with contents, which details what this book is about, or else
an unerring sense of timelessness, those words are as flick through the book and take a look at some of the
appropriate now as they were then. Unsurprisingly great figures that researchers have kindly supplied.
to me, and to many others, they are applicable to the In mapping out the indigenous microbiota of humans,
science of bacteriology as well as to so many other anyone whose life has been pervaded by Dylan’s lyrics
aspects of our existence. Hence, for many years, the pri- cannot fail to see parallels. Bob – how come you knew
mary focus of the vast majority of bacteriologists study- all this bacteriology? Which of the large variety of possi-
ing the bacterial inhabitants of humans has been those ble primary, secondary, and subsequent colonizers
species responsible for disease, e.g. Streptococcus pyo- arriving at any site is certainly determined by A Simple
genes, Haemophilus influenzae, Neisseria meningitidis, Twist of Fate? But when a lonely bacterium’s “gravity
Staphylococcus aureus, etc. What is now a-changing is fails” (Just Like Tom Thumb’s Blues) and it’s deposited on
that interest is shifting towards the vast majority of our the vast acidic, dry surfaces of the forearm, leg, or hand,
microbial partners that do not cause disease and, does it cry out in desperation “oh my God am I here all
indeed, are essential to our well being. The indigenous alone?” (Ballad of a Thin Man). But it’s unlikely to suffer
microbiota of healthy humans is now the subject of for very long as the number of bacteria managing to
intense scrutiny, and its enormous diversity and the survive there is minimized by “Shedding off one more
crucial roles that it plays in the development, protec- layer of skin” (Jokerman).
tion, and maintenance of Homo sapiensare slowly being To me, the colon, with its immense numbers of
revealed. In this book, I have concentrated on the first tightly packed microbes, is epitomized by that incred-
of these, and have described the nature of the microbial ible line from Leopard Skin Pill Box Hat – “it balances on
communities that inhabit the various regions of the your head just like a mattress balances on a bottle of
healthy human body. I have also attempted to explain wine”. How can so many microbes be fitted into such a
their presence at a particular site in terms of the envi- small space, and how can such a sentence be fitted into
ronmental factors that operate there. This book, I hope, the song without breaking its rhythm? Idiot Wind, with
will be useful to undergraduates and postgraduates on its acidic, bile-ridden lyrics just has to be the duodenum
courses in microbiology, medical microbiology, micro- – one of the most acidic regions of the body and perme-
bial ecology, infectious diseases, immunology, human ated by bile salts. The chances of bacteria surviving
biology, medicine, dentistry, nursing, health sciences, there are low, and the chances of love flourishing in
biomedical sciences, and pharmacy and, indeed, to all that relationship are zero. Who could fail to Pity the
those who have an interest in the complex microbial Poor Immigrant bacteria in the urethra – repeatedly
communities with which we have co-evolved. flushed away by a regular dowsing of urine. For them,
I am not sure why books need a preface, and I cannot there’s nothing but Trouble. Is there nowhere they can
recall ever having read one. Nevertheless, it does give get Shelter from the Storm? And spare a thought for those
the author an opportunity for self-indulgence and I am, poor bacteria trying to colonize the conjunctiva who
therefore, going to amuse myself by interweaving two are washed away by “buckets of tears” (Buckets of Rain)
important threads in my life – bacteriology and Dylan. – they must have the feeling that they’re Going,going,
Any reader who is not a Dylan fan should read no gone. And lastly, of course, don’t forget the microbial
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x Preface
transients – those that are “the searching ones, on their Inside the terminal urethra
speechless, seeking trail” (Chimes of Freedom) who have Staphylococci hold on tight
“no direction home, like a complete unknown, like a But most of the urinary tract is sterile
rolling stone” (Like a Rolling Stone). Someone needs to Thanks to innate immunity’s might.
tell them that “Somewhere in this universe there’s a A male’s reproductive system is arid
place that you can call home” (We Better Talk this Over). But with microbes a female’s abounds
Finally, in gratitude to Bob Dylan for all his songs and With lactobacilli and other genera
the effect they’ve had on my life, I dedicate to him my Their variety astounds.
own composition Microbiota Row. It’s to be sung (if But hormones have a great effect
you’re a great singer like me) to the tune of Desolation On which microbes there can grow
Rowor, if you can’t sing, then you can simply recite it to And their relative proportions
the rhythm of that truly amazing song. Change as time’s stream does flow.
From the mouth down to the rectum
MICROBIOTA ROW The intestinal tract unwinds
Producing ecosystems so complex
The eyes have a microbiota And microbiotas of many kinds.
That’s very sparse indeed The oral cavity is aswarming
A few Gram-positive cocci With 800 taxa there
Scavenge from tears all that they need. While the hostile, acidic stomach
The skin has a denser population Apart from H. pyloriis almost bare.
P. acnesis plentifully found The small intestine is nearly sterile
While coryneforms and staphylococci But the colon is replete
Are invariably around. With almost a thousand species
But molecular tools have shown us And without them we’re incomplete.
There’s much more still to know
About the microbes that live upon us Yes, I know you think they’re nasty
And even help us grow. Those minutest forms of life
Your mother said that they were dirty
The respiratory tract is moist and inviting And would only cause you strife.
With food aplenty there But they’re essential for your survival
But of the mucociliary escalator Believe me you really must
All microbes must beware. They digest our food and protect us from
Yet haemophili and streptococci Pathogens that would make us dust.
And Neisseriacan survive Most of our indigenous microbes
While Mollicutesand Moraxella Play a beneficial role, so please
Will there be found alive. Don’t disturb or try to remove them
But there are pathogens among them The result would be disease.
Most deadly, that’s for sure
Armed with many deadly toxins Michael Wilson
To bring us to death’s door
