Comparative Genomic Analyses and CRISPR-Cas Characterization of Cutibacterium acnes Provide Insights Into Genetic Diversity and Typing Applications.

Rodolphe Barrangou,Natalia Cobian,Allison Garlet,Claudio Hidalgo-Cantabrana

doi:10.3389/fmicb.2021.758749

Rodolphe Barrangou, Natalia Cobian + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2021.758749

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Abstract

Cutibacterium acnes is an important member of the human skin microbiome and plays a critical role in skin health and disease. C. acnes encompasses different phylotypes that have been found to be associated with different skin phenotypes, suggesting a genetic basis for their impact on skin health. Here, we present a comprehensive comparative analysis of 255 C. acnes genomes to provide insights into the species genetic diversity and identify unique features that define various phylotypes. Results revealed a relatively small and open pan genome (6,240 genes) with a large core genome (1,194 genes), and three distinct phylogenetic clades, with multiple robust sub-clades. Furthermore, we identified several unique gene families driving differences between distinct C. acnes clades. Carbohydrate transporters, stress response mechanisms and potential virulence factors, potentially involved in competitive growth and host colonization, were detected in type I strains, which are presumably responsible for acne. Diverse type I-E CRISPR-Cas systems and prophage sequences were detected in select clades, providing insights into strain divergence and adaptive differentiation. Collectively, these results enable to elucidate the fundamental differences among C. acnes phylotypes, characterize genetic elements that potentially contribute to type I-associated dominance and disease, and other key factors that drive the differentiation among clades and sub-clades. These results enable the use of comparative genomics analyses as a robust method to differentiate among the C. acnes genotypes present in the skin microbiome, opening new avenues for the development of biotherapeutics to manipulate the skin microbiota.

Highlights

The Gram-positive anaerobic Cutibacterium acnes is one of the most dominant species in the pilosebaceous follicle and a key member of the human skin microbiome (Dreno et al, 2018)
The “typical” C. acnes genome is similar to C. avidum (2.5 Mbp), but slightly bigger than other Cutibacterium species like C. granulosum (2.18 Mbp)
The Propionibacterium genus, where C. acnes was previously classified (Scholz and Kilian, 2016), contains species which genome size ranging between 2.6 and 5 Mbp, with a 67% GC content, relatively higher than the 60% displayed by C. acnes

Summary

Introduction

The Gram-positive anaerobic Cutibacterium (formerly Propionibacterium) acnes is one of the most dominant species in the pilosebaceous follicle and a key member of the human skin microbiome (Dreno et al, 2018). Due to the clinical importance of acne vulgaris, there is increasing interest in studying the skin microbiome and deciphering differences between healthy and disease populations regarding microbial, immunological and hormonal factors (Lee et al, 2019; McLaughlin et al, 2019; Ramasamy et al, 2019; Szegedi et al, 2019), as well as in other skin disease like rosacea (Thompson et al, 2020; Woo et al, 2020). A healthy skin typically presents a more balanced distribution of diverse C. acnes phylotypes compared to acnes disease, where lower diversity is often associated with type IA1 enrichment. Unraveling the unique genetic determinants associated with each clade and sub-clade of this particular species will provide new insights into the skin microbiome, the virulence or pathogenicity of specific sub-clades and the skin virome based on the CRISPR spacers content

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