Regulation of Monospecies and Mixed Biofilms Formation of Skin Staphylococcus aureus and Cutibacterium acnes by Human Natriuretic Peptides

Staphylococcus aureus and Cutibacterium acnes are common representatives of the human skin microbiome. However, when these bacteria are organized in biofilm, they could be involved in several skin disorders such as acne or psoriasis. They inhabit in hollows of hair follicles and skin glands, where they form biofilms. There, they are continuously exposed to human hormones, including human natriuretic peptides (NUPs). We first observed that the atrial natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP) have a strong effect S. aureus and C. acnes biofilm formation on the skin. These effects are significantly dependent on the aero-anaerobic conditions and temperature. We also show that both ANP and CNP increased competitive advantages of C. acnes toward S. aureus in mixed biofilm. Because of their temperature-dependent effects, NUPs appear to act as a thermostat, allowing the skin to modulate bacterial development in normal and inflammatory conditions. This is an important step toward understanding how human neuroendocrine systems can regulate the cutaneous microbial community and should be important for applications in fundamental sciences, medicine, dermatology, and cosmetology

Multiple Drug-Induced Stress Responses Inhibit Formation of Escherichia coli Biofilms

In most ecosystems, bacteria exist primarily as structured surface-associated biofilms that can be highly tolerant to antibiotics and thus represent an important health issue. Here, we explored drug repurposing as a strategy to identify new antibiofilm compounds, screening over 1,000 compounds from the Prestwick Chemical Library of approved drugs for specific activities that prevent biofilm formation by Escherichia coli. Most growth-inhibiting compounds, which include known antibacterial but also antiviral and other drugs, also reduced biofilm formation. However, we also identified several drugs that were biofilm inhibitory at doses where only a weak effect or no effect on planktonic growth could be observed. The activities of the most specific antibiofilm compounds were further characterized using gene expression analysis, proteomics, and microscopy. We observed that most of these drugs acted by repressing genes responsible for the production of curli, a major component of the E. coli biofilm matrix. This repression apparently occurred through the induction of several different stress responses, including DNA and cell wall damage, and homeostasis of divalent cations, demonstrating that biofilm formation can be inhibited through a variety of molecular mechanisms. One tested drug, tyloxapol, did not affect curli expression or cell growth but instead inhibited biofilm formation by suppressing bacterial attachment to the surface. IMPORTANCE The prevention of bacterial biofilm formation is one of the major current challenges in microbiology. Here, by systematically screening a large number of approved drugs for their ability to suppress biofilm formation by Escherichia coli, we identified a number of prospective antibiofilm compounds. We further demonstrated different mechanisms of action for individual compounds, from induction of replicative stress to disbalance of cation homeostasis to inhibition of bacterial attachment to the surface. Our work demonstrates the potential of drug repurposing for the prevention of bacterial biofilm formation and suggests that also for other bacteria, the activity spectrum of antibiofilm compounds is likely to be broad

Epinephrine Affects Ribosomes, Cell Division, and Catabolic Processes in <i>Micrococcus luteus</i> Skin Strain C01: Revelation of the Conditionally Extensive Hormone Effect Using Orbitrap Mass Spectrometry and Proteomic Analysis

In the current study, extensive Orbitrap mass spectrometry analysis was conducted for skin strain Micrococcus luteus C01 planktonic cultures and biofilms after 24 h and 72 h of incubation either in the presence of epinephrine or without any implementations. The investigation revealed the complex and conditionally extensive effect of epinephrine at concentrations closer to normal blood plasma concentrations on both planktonic cultures and biofilms of skin strain M. luteus C01. The concentrations of hundreds of proteins changed during the shift from planktonic growth mode to biofilm and hundreds of proteins were downregulated or upregulated in the presence of epinephrine. Ribosomal, TCA, and cell division proteins appear to be the most altered in their amounts in the presence of the hormone. Potentially, the regulatory mechanism of this process is connected with c-di-GMP and histidine kinases, which were affected by epinephrine in different samples. The phenomenon of epinephrine-based biofilm regulation in M. luteus C01 has wide implications for microbial endocrinology and other research areas

Regulation of Monospecies and Mixed Biofilms Formation of Skin Staphylococcus aureus and Cutibacterium acnes by Human Natriuretic Peptides

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Table_3_Epinephrine extensively changes the biofilm matrix composition in Micrococcus luteus C01 isolated from human skin.docx

The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we continued and extended the research of epinephrine effects on the skin commensal Micrococcus luteus C01 and its biofilms, and also the matrix changes during the biofilm growth. Epinephrine in concentration 4.9 × 10–9 M which is close to normal blood plasma level increased the amount of polysaccharides and extracellular DNA in the matrix, changed extensively its protein, lipid and polysaccharide composition. The Ef-Tu factor was one of the most abundant proteins in the matrix and its amount increased in the presence of the hormone. One of the glucose-mannose polysaccharide was absent in the matrix in presence of epinephrine after 24 h of incubation. The matrix phospholipids were also eradicated by the addition of the hormone. Hence, epinephrine has a great impact on the M. luteus biofilms and their matrix composition, and this fact opens wide perspectives for the future research.</p

Data_Sheet_1_Epinephrine extensively changes the biofilm matrix composition in Micrococcus luteus C01 isolated from human skin.DOCX

The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we continued and extended the research of epinephrine effects on the skin commensal Micrococcus luteus C01 and its biofilms, and also the matrix changes during the biofilm growth. Epinephrine in concentration 4.9 × 10–9 M which is close to normal blood plasma level increased the amount of polysaccharides and extracellular DNA in the matrix, changed extensively its protein, lipid and polysaccharide composition. The Ef-Tu factor was one of the most abundant proteins in the matrix and its amount increased in the presence of the hormone. One of the glucose-mannose polysaccharide was absent in the matrix in presence of epinephrine after 24 h of incubation. The matrix phospholipids were also eradicated by the addition of the hormone. Hence, epinephrine has a great impact on the M. luteus biofilms and their matrix composition, and this fact opens wide perspectives for the future research.</p