Comparative Proteomic Analysis of Membrane Vesicles from Clinical C. acnes Isolates with Differential Antibiotic Resistance

Abstract

Purpose Cutibacterium acnes ( C. acnes ) is closely associated with the pathogenesis of acne, and antibiotics targeting C. acnes have been widely used for decades. However, antibiotic resistance has been increasing rapidly. Membrane vesicles (MVs) have been found to play important roles in antibiotic resistance in some bacteria. We aimed to explore the mechanism of antibiotic resistance and the virulence components within C. acnes -derived MVs. Materials and Methods We isolated clinical C. acnes strains from the lesions of acne patients who were sensitive or resistant to the antibiotics erythromycin and clindamycin. We analyzed the proteome of MVs from four sensitive C. acnes isolates and three resistant isolates by LC-MS/MS. Results We identified 543 proteins within the MVs of clinical C. acnes strains. Several lipases, NlpC/P60, CAMP factor, and Hta domain protein were detected as virulence factors in the C. acnes -derived MVs. The levels of two lipases and FtsZ were significantly higher in resistant C. acnes -derived MVs compared with sensitive strains (p < 0.05). Conclusion According to the implications of this study, improper antibiotic use might not only increase antibiotic resistance in C. acnes but could also further alter the cutaneous lipid composition and aggravate host inflammation, thus resulting in worse clinical manifestations in acne patients. This study re-emphasizes that the improper use of antibiotics should be treated more seriously in clinical practice. Furthermore, to combat multidrug resistance in C. acnes , this study suggests that FtsZ inhibitors could be useful.

Cannabidiol Inhibits Inflammation Induced by Cutibacterium acnes-Derived Extracellular Vesicles via Activation of CB2 Receptor in Keratinocytes

“…The structure and size of CEVs were analyzed by transmission electron microscopy (TEM) (JEM 2100, Tokyo, Japan) as previously described. 21 …”

“…The structure and size of CEVs were analyzed by transmission electron microscopy (TEM) (JEM 2100, Tokyo, Japan) as previously described. 21 Cell Culture and Intervention NHEKs were isolated from human foreskin tissues according to the method described previously and were cultured in Keratinocyte Growth Medium 2 (KGM2) (PromoCell, #C-20011, Heidelberg, Germany) under standard conditions. 22 Cells were seeded into 6-well culture plates at a cell density of 1×10 5 cells per well.…”

Loaded delta-hemolysin shapes the properties of Staphylococcus aureus membrane vesicles

“…A total of 431 proteins have been identified from MVs of the gram-positive pathogen Clostridium perfringens strain CP4 by using 1D gel separation and LC-MS/MS analysis (Jiang et al, 2014). With label-free quantitative LC-MS/MS determination, 543 proteins are characterized from MVs of a clinical isolate Cutibacterium acnes (Jiang et al, 2022). Lee et al (2009) first discovered MV release in S. aureus ATCC14458 and identified approximately 90 proteins in the MVs through nano-LC-ESI-MS/MS.…”

Interactions between extracellular vesicles and microbiome in human diseases: New therapeutic opportunities

“…Keratinocytes are the main cell type of the epidermis and participate in the activation of inflammation and immune responses when exposed to DAMPs and PAMPs. Proteomic analysis identified multiple virulence factors (such as NlpC/P60, CAMP factor, and Hta domain protein) in C. acnes ‐derived BEVs [ 172 ]. Meanwhile, C. acnes ‐derived BEVs significantly induced IL‐8 and GM‐CSF production and dysregulated epidermal differentiation in epidermal keratinocytes, leading to acne‐like phenotypes [ 173 ].…”