C-Type Natriuretic Peptide Acts as a Microorganism-Activated Regulator of the Skin Commensals Staphylococcus epidermidis and Cutibacterium acnes in Dual-Species Biofilms

SIMPLE SUMMARY: Commensal (‘friendly’) microbes protect our skin from the invasion of pathogens and provide benefits for the human immune system. The microbial community exists in different microniches of the skin in the form of a biofilm—a highly organized microbial community, with properties different from traditionally studied planktonic cultures. The two most abundant skin commensals, Staphylococcus epidermidis and Cutibacterium acnes, can form biofilms inside hair follicles and sebaceous glands, and the behavior of these bacteria can maintain skin health. The study of the potential regulation of the skin microbial community (skin microbiota) by human hormones and particularly by human natriuretic peptides (NUP) has wide perspectives because of a data shortage, hormone potential to regulate the microbial community, and potential approaches in clinical practice. We used different methods to evaluate the impact of C-type natriuretic peptide (CNP) on monospecies and dual species biofilms of C. acnes and S. epidermidis, and we found that CNP boosts the competitive properties of C. acnes in the presence of S. epidermidis. Additionally, we found genes which are potential targets of CNP, hence, we made a step towards a better understanding of how peptides regulate the behavior of cutaneous bacteria populations. ABSTRACT: The effect of C-type natriuretic peptide in a concentration closer to the normal level in human blood plasma was studied on the mono-species and dual-species biofilms of the skin commensal bacteria Cutibacterium acnes HL043PA2 and Staphylococcus epidermidis ATCC14990. Despite the marginal effect of the hormone on cutibacteria in mono-species biofilms, the presence of staphylococci in the community resulted in a global shift of the CNP effect, which appeared to increase the competitive properties of C. acnes, its proliferation and the metabolic activity of the community. S. epidermidis was mostly inhibited in the presence of CNP. Both bacteria had a significant impact on the gene expression levels revealed by RNA-seq. CNP did not affect the gene expression levels in mono-species cutibacterial biofilms; however, in the presence of staphylococci, five genes were differentially expressed in the presence of the hormone, including two ribosomal proteins and metal ABC transporter permease. In staphylococci, the Na-translocating system protein MpsB NADH-quinone oxidoreductase subunit L was downregulated in the dual-species biofilms in the presence of CNP, while in mono-species biofilms, two proteins of unknown function were downregulated. Hypothetically, at least one of the CNP mechanisms of action is via the competition for zinc, at least on cutibacteria.