The human skin microbiome in acne at the strain level

Huiying LiDepartment of Molecular and Medical Pharmacology

UCLA

September 24, 2013

Human skin microbiome

http://www.acne.org/whatisacne.html

• Skin is the first line of defense against pathogens.

• The external surface of the human skin harbors 200‐300 bacterial species. The number of bacterial cells of the skin is on the order of 1012.

• Different skin sites (dry, moist, or sebaceous) harbor distinct microbial communities.

• We are interested in studying the human skin microbiome in the pilosebaceous unit and its association with skin diseases.

Acne vulgaris• Acne is the most common skin disorder affecting approximately 50

million people in the States.  More than 80% of the population suffers from acne at some point in their life.

• Acne is most prevalent during the middle‐to‐late teenage period. • Acne can be extremely painful.  It has significant morbidity and

profoundly affects patients’ self‐esteem, especially in adolescent population.

• Two main types of treatments: antibiotics and retinoids. • Economically, it is estimated that U.S. consumers spend more than 

1.2 billion dollars each year for the treatment of acne.• The etiology of acne is still unclear.  A bacterial factor has been 

believed to be one of the mechanisms contributing to acne.

Modified from Strauss and Thiboutot et al.

Pilosebaceous unit has a tractable microbiome with a single dominant species

The microcomedone is dominated by one bacterial species, Propionibacterium acnes (87%).This system offers a unique advantage allowing in‐depth analysis of a human microbiome at the strain level.

P. acnes 84.3%P. acnes 84.3%P. acnes 87%

• P. acnes is a Gram‐positive, anaerobic bacillus that colonizes human skin.

• P. acnes has been implicated as a pathogenic factor in acne.

• In inflammatory acne, P. acnes plays a key role in eliciting a host inflammatory response that is thought to be important for the pathogenesis of the disease.

• Antibiotic therapy targeting P. acnes has been a mainstay treatment for more than 30 years.

Propionibacterium acnes

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

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Pooled normal skin samples by metagenomic shotgun sequencingSamples from acne patients Samples from normal individuals

Escherichia coliStaphylococcus capitis

Propionibacterium oral taxon 193Prevotella orisStaphylococcus epidermis

Propionibacterium granulosumPropionibacterium acnes

Otherunclassified Corynebacterineae

16S rDNA sequencing of samples from acne patients and normal individuals

0

1000

2000

3000

4000

5000

6000

Number of clones

Top 30 ribotypes ordered by abundance

AcneNormal

A few major ribotypes dominate the microbiome in pilosebaceous units

Ribotype Nucleotide changes from RT1

Number of subjects

Number of clones

Percentage of clones from acne patientsa

Percentage of clones

from normal individualsb

p-valuec

RT1 - 90 5536 48% 52% 0.84

RT2 T854C 48 1213 51% 49% 0.36

RT3 T1007C 60 2104 40% 60% 0.092

RT4 G1058C, A1201C 23 275 84% 16% 0.049

RT5 G1058C 15 205 99% 1% 0.00050

RT6 T854C, C1336T 11 262 1% 99% 0.025

RT7 G529A 10 188 99% 1% 0.12

RT8 G1004A, T1007C 5 239 100% 0% 0.024

RT9 G1268A 4 68 99% 1% 0.29

RT10 T554C, G1058C 5 61 100% 0% 0.024

Some of the major ribotypes are associated with acne or normal skin

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

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es

RT10

RT9

RT8

RT7

RT6

RT5

RT4

RT3

RT2

RT1

I III II IIIIII I

V V

Normal (n=51)Acne (n=48)I IIIIIIV V

Microbiome type I Microbiome type II Microbiome type IIIMicrobiome type IV Microbiome type V Minor microbiome types

Five main microbiome types

Acne

Normal

P. acnes population structures differ in acne and normal skin

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

RT10

RT9

RT8

RT7

RT6

RT5

RT4

RT3

RT2

RT1

I IIIIIIV V

Microbiome type I Microbiome type II Microbiome type III

Microbiome type IV Microbiome type V Minor microbiome types

Samples in this study Samples in HMP dataset Samples in Grice et al. 2009

I IIIIIIVV

Five main microbiome types were also observed in other cohort datasets

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Acne in this study

Normal in this study

HMP Grice et al. 2009 Grice et al. 2009, HV4 removed

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RT10

RT9

RT8

RT7

RT6

RT5

RT4

RT3

RT2

RT1

RT6 is also abundant in the HMP cohort

• The first P. acnes genome was published in 2004 (Bruggemann H et al.). The genome sequence of KPA171202 is 2.6Mb encoding 2,333 ORFs.  

• To understand the strain differences at the genome level, we isolated over 1,000 P. acnes strains from over 200 samples.  67 strains covering RT1, RT2, RT3, RT4, RT5, RT6 and RT8 were selected for sequencing to high quality genome drafts.  12 genomes were complete and finished. 

• There are additional 13 P. acnes genomes publically available.

P. acnes genomes

0.01Disease associated

Health associated

IA-1

IA-2

IB-1

IB-2

II

0.01

IB-3

Distinct lineages of P. acnes strains associated with acne or normal skin

HL036PA1 HL036PA2 HL036PA3 HL046PA2 HL002PA3 HL002PA2 HL005PA3 HL005PA2 HL020PA1 HL027PA2 HL100PA1 HL087PA2 HL013PA2 HL063PA1 HL096PA3 J165 HL072PA1 HL072PA2 HL078PA1 SK137 HL106PA2 HL099PA1 HL083PA1 HL038PA1 HL005PA1 HL074PA1 HL007PA1 HL096PA2 HL096PA1 HL043PA1 HL043PA2 HL056PA1 HL053PA1 HL045PA1 HL025PA1 SK187 HL086PA1 HL082PA1 HL110PA2 HL053PA2 HL110PA1 HL092PA1 HL063PA2 HL030PA2 HL037PA1 HL059PA1 HL059PA2 HL025PA2 HL067PA1 HL005PA4 HL002PA1 HL027PA1 HL083PA2 HL046PA1 HL013PA1 HL087PA1 HL087PA3 HL050PA1 HL050PA3 HL097PA1 HL030PA1 KPA171202 HL050PA2 HL060PA1 HL103PA1 HL082PA2 HL001PA1 HL106PA1 J139 HL110PA3 HL110PA4

IA-1

Genes 1-300 on the chromosome Genes 1-75 on the plasmid

Locus 2Locus 1

RT1

RT532 (G88A)

RT2 (T854C) RT3 (T1007C) RT4 (G1058C, A1201C) RT5 (G1058C)

RT6 (T854C, C1336T) RT8 (G1004A, T1007C) RT16 (C1001T, T1007C)

Locus 3 (plasmid)

Acne index for ribotype 0 20 40 60 80 100 %

Clade

IA-2

IB-1

IB-2

II

Normal Acne

Acne index

IB-3

Log10(distance)RT1 RT2 RT3 RT4 RT5 RT6 RT8 RT16 RT532

HL036PA1 + -3.2 -2.6 -2.1 -2.0 -2.1 -2.0 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.1 -2.0 -2.1 -2.0 -2.1 -2.1 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL036PA2 + -3.2 -2.6 -2.1 -2.0 -2.1 -2.0 -2.1 -2.1 -2.0 -2.1 -2.1 -2.1 -2.1 -2.0 -2.0 -2.0 -2.1 -2.1 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL036PA3 + -2.6 -2.6 -2.1 -2.0 -2.1 -1.9 -2.1 -2.1 -2.0 -2.0 -2.1 -2.1 -2.1 -2.0 -2.0 -2.0 -2.1 -2.1 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL005PA3 + -2.1 -2.1 -2.1 -2.5 -2.3 -2.1 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.0 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL005PA2 + -2.0 -2.0 -2.0 -2.5 -2.1 -2.0 -2.1 -2.1 -2.0 -2.0 -2.1 -2.1 -2.1 -2.0 -2.0 -1.9 -1.9 -1.9 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL020PA1 - -2.1 -2.1 -2.1 -2.3 -2.1 -2.1 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL027PA2 - -2.0 -2.0 -1.9 -2.1 -2.0 -2.1 -2.1 -2.0 -2.0 -2.0 -2.0 -2.0 -2.1 -2.0 -2.0 -1.9 -1.9 -1.9 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL100PA1 - -2.1 -2.1 -2.1 -2.2 -2.1 -2.2 -2.1 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.2 -2.0 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

266 - -2.1 -2.1 -2.1 -2.2 -2.1 -2.2 -2.0 -2.2 -2.3 -2.3 -2.3 -2.3 -2.3 -2.2 -2.3 -2.0 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL013PA2 - -2.1 -2.0 -2.0 -2.2 -2.0 -2.2 -2.0 -2.2 -2.3 -2.2 -2.2 -2.2 -2.3 -2.2 -2.2 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL087PA2 - -2.1 -2.1 -2.0 -2.2 -2.0 -2.2 -2.0 -2.2 -2.3 -2.2 -2.3 -2.2 -2.3 -2.2 -2.2 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL063PA1 - -2.1 -2.1 -2.1 -2.2 -2.1 -2.2 -2.0 -2.2 -2.3 -2.2 -2.3 -2.3 -2.4 -2.3 -2.3 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL096PA3 - -2.1 -2.1 -2.1 -2.2 -2.1 -2.2 -2.0 -2.2 -2.3 -2.2 -2.2 -2.3 -2.4 -2.3 -2.3 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

J165 - -2.1 -2.1 -2.1 -2.2 -2.1 -2.2 -2.1 -2.2 -2.3 -2.3 -2.3 -2.4 -2.4 -2.5 -2.5 -2.0 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL072PA2 + -2.0 -2.0 -2.0 -2.2 -2.0 -2.2 -2.0 -2.2 -2.2 -2.2 -2.2 -2.3 -2.3 -2.5 -3.0 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL072PA1 + -2.1 -2.0 -2.0 -2.2 -2.0 -2.2 -2.0 -2.2 -2.3 -2.2 -2.2 -2.3 -2.3 -2.5 -3.0 -1.9 -2.0 -2.0 -1.1 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.3 -1.1 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.6 -0.6 -0.8 -0.8 -0.8 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

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HL087PA1 + -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.9 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.7 -1.6 -1.7 -1.7 -1.8 -2.2 -2.3 -2.4 -2.5 -2.5 -2.5 -2.5 -2.5 -2.5 -2.6 -2.6 -2.2 -2.6 -3.3 -0.7 -0.7 -0.8 -0.8 -0.8 -0.3 -0.2 -0.2 -0.2 -0.3 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL087PA3 + -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -0.9 -1.2 -1.0 -1.0 -1.0 -1.0 -1.0 -1.0 -1.7 -1.6 -1.7 -1.7 -1.8 -2.2 -2.3 -2.4 -2.5 -2.5 -2.5 -2.5 -2.5 -2.5 -2.6 -2.6 -2.2 -2.6 -3.3 -0.7 -0.7 -0.8 -0.8 -0.8 -0.3 -0.2 -0.2 -0.2 -0.3 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

HL097PA1 - -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -2.8 -0.5 -0.5 -0.5 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

PRP-38 - -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.6 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -2.8 -0.5 -0.5 -0.5 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2

6609 - -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.9 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.5 -0.5 -2.4 -2.4 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3

KPA171202 - -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.9 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.5 -0.5 -2.4 -2.4 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3

HL030PA1 - -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.9 -0.7 -0.7 -0.7 -0.7 -0.7 -0.7 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.8 -0.5 -0.5 -2.4 -2.4 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3

HL050PA2 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.2 -0.2 -0.3 -0.3 -0.3 -1.1 -1.2 -1.2 -1.1 -1.1 -1.0 -1.0 -1.0 -1.0 -1.0

HL060PA1 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.1 -1.8 -1.7 -1.4 -1.2 -1.2 -1.2 -1.2 -1.2 -1.2

HL103PA1 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.2 -1.8 -1.8 -1.5 -1.3 -1.2 -1.2 -1.2 -1.2 -1.2

HL082PA2 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.2 -1.7 -1.8 -1.4 -1.3 -1.2 -1.2 -1.2 -1.2 -1.2

HL001PA1 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.3 -0.2 -0.3 -0.3 -0.3 -0.2 -0.2 -0.3 -0.3 -0.3 -1.1 -1.4 -1.5 -1.4 -1.3 -1.2 -1.2 -1.2 -1.2 -1.2

HL106PA1 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.1 -1.2 -1.3 -1.3 -1.3 -1.6 -1.6 -1.5 -1.5 -1.5

J139 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.0 -1.2 -1.2 -1.2 -1.2 -1.6 -2.2 -1.8 -1.8 -1.9

ATCC11828 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.0 -1.2 -1.2 -1.2 -1.2 -1.6 -2.2 -1.8 -1.8 -1.8

HL110PA4 + -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.0 -1.2 -1.2 -1.2 -1.2 -1.5 -1.8 -1.8 -2.5 -2.4

HL110PA3 + -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.0 -1.2 -1.2 -1.2 -1.2 -1.5 -1.8 -1.8 -2.5 -2.3

HL042PA3 - -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.2 -0.3 -0.3 -0.3 -1.0 -1.2 -1.2 -1.2 -1.2 -1.5 -1.9 -1.8 -2.4 -2.3

IB-1

IB-2

ICIB-3

II

IA-1

IA-2

RecAType II

RecAType IA

RecAType IB

-3.6 -3.4 -3.2 -3.0 -2.8 -2.6 -2.4 -2.2 -2.0 -1.8 -1.6 -1.4 -1.2 -1.0 -0.8 -0.6 -0.4 -0.2

Pair‐wise distance among the strains 

RT4 and RT5 strains appear to be clonal.

E. coli K-12 W3110

P. acnes isolates with ribotypes 2 and 6

L T

L T

GAGTTCCCCGCGCCAGCGGGGATAAACCG

GTATTCCCCGCCTATGCGGGGGTGAGCC

Cas3 Cse1 Cse2 Cse4 Cas5 Cse3 Cas1 Cas2

ygcK ygcJ ygcI ygcH ygbT ygbFygcLygcB

RT2 and RT6 strains harbor CRISPR/cas

Closely related strains share CRISPR spacers

Some of the spacers encode sequences matching to loci 2 and 3 in RT4 and RT5.

HL060PA1 S1 S2HL103PA1 S3**HL082PA2 S4** S2HL001PA1 S5 S5 S5 S6 S7HL106PA1 S8 S9 S10 S11 S12 S13 S14 S15** S16J139 S17* S18ATCC11828 S19 S17* S18HL110PA4 S20 S21 S22 S23 S24 S25 S26 S17* S18HL110PA3 S20 S21 S22 S23 S24 S25 S26 S17* S18HL042PA3 S27 S28 S29 S17*HL202PA1 S17* S18

Conclusions• P. acnes is the dominant species in the pilosebaceous unit on 

human skin.

• The relative abundances of P. acnes are similar in acne patients and normal individuals, however, the population structure at the strain level is significantly different betweenthe two cohorts. 

• We found that RT4, RT5 and RT8 strains were highly associated with acne, and RT6 was enriched in healthy skin.

• We identified potential genetic determinants of various P. acnes strains in association with acne or health.

• Acquired DNA sequences and bacterial immune elements may play roles in determining virulence properties of P. acnesstrains and some could be novel targets for therapeutic interventions.

AcknowledgementsLi LabShuta TomidaSorel Fitz‐GibbonBor‐Han ChiuLin NguyenGabriela KasimatisJared LiuDezhi KangBaochen ShiRiceley YanQiao ZhongChristine DuSam NgoMarthew Wong

Harbor‐UCLA Medical CenterNoah Craft, Crisel Erfe

Washington UniversityGeorge Weinstock, Erica Sodergren 

UCLAJeff F. Miller, Minghsun LiuJenny Kim, David ElashoffRobert Modlin, Anya Loncaric

FundingNIAMSNIGMS

http://labs.pharmacology.ucla.edu/lilab/

Vision-Integrity-Passion