Heterogeneity and antibiotic resistance in <i>Propionibacterium acnes</i>
 isolates and its therapeutic implications: blurring the lines between commensal and pathogenic phylotypes

Sadhasivam, Suresh; Sinha, Mau; Saini, Swamini; Kaur, Simran; Gupta, Tanvi; Sengupta, Shiladitya; Ghosh, Shamik; Sardana, Kabir

doi:10.1111/dth.12391

Cited by 19 publications

(15 citation statements)

References 13 publications

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“…68 Focusing on the molecular mechanism involved in this resistance, the authors further demonstrated that most of the clinical strains belonged to phylotype IA1 38 . In a recent case report, 69 bacterial isolates from a slow responder to antimicrobial treatments were found to be phylogenetically heterogeneous and presented variable resistance to clindamycin. In a surprising manner the pathogenic phylotype IA1 displayed clindamycin sensitivity, whereas phylotype IB, associated with commensals, exhibited high clindamycin resistance.…”

Section: Acnes Response To Antibioticsmentioning

confidence: 99%

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

Dréno

Pécastaings

Corvec

et al. 2018

Acad Dermatol Venereol

427

317

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While the commensal bacterium Propionibacterium acnes (P. acnes) is involved in the maintenance of a healthy skin, it can also act as an opportunistic pathogen in acne vulgaris. The latest findings on P. acnes shed light on the critical role of a tight equilibrium between members of its phylotypes and within the skin microbiota in the development of this skin disease. Indeed, contrary to what was previously thought, proliferation of P. acnes is not the trigger of acne as patients with acne do not harbour more P. acnes in follicles than normal individuals. Instead, the loss of the skin microbial diversity together with the activation of the innate immunity might lead to this chronic inflammatory condition. This review provides results of the most recent biochemical and genomic investigations that led to the new taxonomic classification of P. acnes renamed Cutibacterium acnes (C. acnes), and to the better characterisation of its phylogenetic cluster groups. Moreover, the latest data on the role of C. acnes and its different phylotypes in acne are presented, providing an overview of the factors that could participate in the virulence and in the antimicrobial resistance of acne-associated strains. Overall, this emerging key information offers new perspectives in the treatment of acne, with future innovative strategies focusing on C. acnes biofilms and/or on its acne-associated phylotypes.

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Section: Acnes Response To Antibioticsmentioning

confidence: 99%

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

Dréno

Pécastaings

Corvec

et al. 2018

Acad Dermatol Venereol

427

317

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“…In this study, dead P. acnes was used to induce inflammation in both in vitro and in vivo models to evaluate The position of mutation in the nucleotide residue (Escherichia coli numbering) of 23S ribosomal RNA is mentioned in parentheses. A2058G mutation is associated with higher degree of clindamycin resistance, whereas A2059G mutation confers clindamycin susceptibility (Sadhasivam et al, 2016).…”

Section: Discussionmentioning

confidence: 98%

“…Next, we tested VCD-004 using a library of P. acnes clinical isolates with a diverse resistance spectrum to clindamycin and erythromycin (Sadhasivam et al, 2016). These isolates had mutations either in A2058G or A2059G (Escherichia coli numbering) in bacterial 23S peptidyl ribosomal RNA that conferred resistance or susceptibility to clindamycin, respectively.…”

Section: Rational Design and Synthesis Of Vcd Antibioticsmentioning

confidence: 99%

A Rationally Designed Multifunctional Antibiotic for the Treatment of Drug-Resistant Acne

Ghosh

Sinha

Bhattacharyya

et al. 2018

Journal of Investigative Dermatology

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Acne is a multifactorial skin disease, underpinned by colonization of Propionibacterium acnes and inflammation. The emergence of resistant P. acnes strains has affected the current acne treatment algorithm. This setback served as an impetus for rationally designing a library of next-generation antibiotics that exhibit a bactericidal effect on resistant P. acnes and exert an immunomodulatory function to reduce inflammation. In silico screening showed that one of the molecules, VCD-004, exhibits improved mode of binding to bacterial DNA gyrase. VCD-004 shows high potency against clinical isolates of resistant P. acnes and excellent efficacy in vivo. Furthermore, VCD-004 exhibits a superior mutant prevention index, suggesting that it impedes the development of resistance better than clindamycin. Additionally, it shows optimal skin penetration and has a potent anti-inflammatory effect via reduction of proinflammatory cytokines (IL-6) independent of its antibacterial action. VCD-004 affects P. acnes-induced nuclear accumulation of NF-κB in THP-1 cells. The in vitro viability of human keratinocytes in the presence of VCD-004 indicates a desirable therapeutic window for topical use. Such rationally designed bactericidal and immunomodulatory dual pharmacophore-based lipophilic molecule(s) can emerge as the next-generation topical therapy for acne with underlying resistant P. acnes etiology.

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“…A2058 (E. coli numbering) residue is one of the pivotal nucleotides for lincosamide binding at the bacterial target [51]. Point mutation at A2058G in 23S rRNA is reported to confer high clindamycin resistance [52]. Similarly, many reports indicate instances of ermX gene-mediated clindamycin and erythromycin resistance in C. acnes [24].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of VB-1953 Topical Gel in Non-Responder Acne Patients with Clindamycin-Resistant Cutibacterium acnes

et al. 2020

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Background and Objectives The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes. Methods An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/ dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients. Results The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p < 0.0001 for both), with an Investigator Global Assessment success of 26.3% at week 12 compared with baseline. Resistant bacteria were reduced by (94.3 ± 1%; p < 0.05) within 12 weeks of treatment with VB-1953. Conclusion These results indicate that VB-1953 topical gel can be a safe and effective therapy for moderate to severe acne with underlying resistant C. acnes in subjects who had not responded to previous antibiotic treatments. Key PointsThe efficacy and safety of the bactericidal antibiotic VB-1953 (2%) topical gel was evaluated for acne treatment in an investigator-initiated, open-label, single-arm study in acne patients who did not respond to or showed poor response to previous clindamycin treatment and had clindamycin-resistant Cutibacterium acnes.In the era of emerging antimicrobial resistance, the selection of VB-1953 for acne treatment can play a key role in improving clinical outcomes in acne patients and in public health.

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Heterogeneity and antibiotic resistance in Propionibacterium acnes isolates and its therapeutic implications: blurring the lines between commensal and pathogenic phylotypes

Cited by 19 publications

References 13 publications

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates

A Rationally Designed Multifunctional Antibiotic for the Treatment of Drug-Resistant Acne

Efficacy and Safety of VB-1953 Topical Gel in Non-Responder Acne Patients with Clindamycin-Resistant Cutibacterium acnes

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