-
Anaerobe Apr 2020FMX101 4% minocycline foam (FMX101 4%) is a novel, topical minocycline formulation for treatment of acne vulgaris. We report that FMX101 4% had an MIC of 0.25 μg/ml...
FMX101 4% minocycline foam (FMX101 4%) is a novel, topical minocycline formulation for treatment of acne vulgaris. We report that FMX101 4% had an MIC of 0.25 μg/ml and was ≥4-fold more active than comparator antimicrobials against a panel of 98 clinical Cutibacterium acnes isolates. The panel was diverse by clonal complex and sequence type, having 20 novel multi-locus sequence types including clonal complexes and sequence types associated with acne (CC1, CC3, and CC4; ST1 and ST3). Some isolates were phenotypically resistant to clindamycin (6.1%), erythromycin (14.3%), and tetracycline (2.0% intermediate resistance). Six isolates (6.4%) carried a mutation in the quinolone resistance-determining region of gyrA. With C. acnes, spontaneous resistance to FMX101 4% occurred at frequencies ranging from ≤5 × 10 to <1 × 10; mutations were identified in rpsJ, a gene encoding 30S ribosomal protein S10. No mutant exhibited a minocycline MIC above 0.5 μg/ml. No second-step mutation in previously isolated mutants or strains containing rpsJ ± 16S rRNA mutations was detected following minocycline challenge. Minocycline retained antibacterial activity against C. acnes over 15 multiple passages; thus, no selective growth advantage for minocycline-resistant mutants occurred under the experimental conditions. FMX101 4% has the potential to retain the favorable resistance profile of minocycline in diverse C. acnes isolates while providing the benefits of a topical formulation for treatment of acne vulgaris.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Genotype; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Mutation; Propionibacterium acnes
PubMed: 32058277
DOI: 10.1016/j.anaerobe.2020.102169 -
Journal of Bacteriology Apr 1963Moore, W. E. C. (Virginia Agricultural Experiment Station, Virginia Polytechnic Institute, Blacksburg) and Elizabeth P. Cato. Validity of Propionibacterium acnes...
Moore, W. E. C. (Virginia Agricultural Experiment Station, Virginia Polytechnic Institute, Blacksburg) and Elizabeth P. Cato. Validity of Propionibacterium acnes (Gilchrist) Douglas and Gunter comb. nov. J. Bacteriol. 85:870-874. 1963.-ATCC strains of Corynebacterium acnes 11827, 6921, and 6922 were tested and consistently found to ferment lactate with the production of propionate, acetate, and succinate under strictly anaerobic conditions. ATCC strains of eight species of Propionibacterium fermented lactate under strictly anaerobic or under deep broth aerobic culture conditions. The ratios of fermentation products of each of the organisms were essentially identical, indicating that C. acnes should properly be classified in the genus Propionibacterium as suggested by Douglas and Gunter. Serological tests demonstrated that this organism shares antigens in common with several of the other species of Propionibacterium.
Topics: Classification; Corynebacterium; Fermentation; Lactic Acid; Propionates; Propionibacterium; Propionibacterium acnes
PubMed: 14044956
DOI: 10.1128/jb.85.4.870-874.1963 -
Steady state and exchange kinetics of pyruvate, phosphate dikinase from Propionibacterium shermanii.The Journal of Biological Chemistry Dec 1976Evidence is presented based on requirements for exchange in the partial reactions, initial velocity and exchange kinetics and product inhibition, that the pyruvate,...
Evidence is presented based on requirements for exchange in the partial reactions, initial velocity and exchange kinetics and product inhibition, that the pyruvate, phosphate dikinase reaction of propionibacteria occurs by a nonclassical Tri Uni Uni Ping Pong mechanism. The mechanism involves a pyrophosphoryl enzyme, a phosphoryl enzyme, and the free enzyme, and three functionally distinct and independent substrate sites. On the first site, there is pyrophosphorylation of the enzyme by ATP with subsequent release of AMP. The pyrophosphoryl moiety then reacts at the second site with Pi yielding the product PPi and the phosphoryl from of the enzyme. At the third site pyruvate is phosphorylated yielding P-enolpyruvate and the free enzyme. The three catalytic sites are proposed to be linked by a histidyl residue which functions as a pyrophosphoyrl- and phosphoryl-carrier between the three sites. This proposal is based on the following observations. (A) The patterns of the double reciprocal plots of the initial velocities were all parallel; (b) product inhibition between each pair of substrates and products of the three partial reactions were competitive, i.e. ATP against AMP, Pi against PPi, and pyruvate against P-enolpyruvate; (c) the other product inhibitions, with one exception, were noncompetitive as required by the nonclassical ping-pong mechanism; (d) ATP or P-enolpyruvate was required for the Pi in equilibrium PPi exchange reaction which is in accord with the participation of a pyrosphosphoryl or phosphoryl form of the enzyme in this exchange; (e) the ATP in equilibrium AMP exchange and pyruvate in equilibrium P-enolpyruvate exchange did not require additional substrates. In addition, the inhibition and participation in the exchange reactions of the alpha,beta and beta,gamma-methylene analogues of ATP and of the methylene analogue of inorganic pyrophosphate were investigated and the results were in accord with the proposed mechanism. The combined evidence provides a well documented example of a three site nonclassical Tri Uni Uni Ping Pong mechanism.
Topics: Adenosine Monophosphate; Binding, Competitive; Diphosphates; Kinetics; Mathematics; Phosphoenolpyruvate; Phosphotransferases; Propionibacterium; Pyruvate, Orthophosphate Dikinase
PubMed: 187600
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Apr 2012Propionibacterium acnes is an important cause of orthopedic-implant-associated infections, for which the optimal treatment has not yet been determined. We investigated...
Propionibacterium acnes is an important cause of orthopedic-implant-associated infections, for which the optimal treatment has not yet been determined. We investigated the activity of rifampin, alone and in combination, against planktonic and biofilm P. acnes in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration (MBC) were 0.007 and 4 μg/ml for rifampin, 1 and 4 μg/ml for daptomycin, 1 and 8 μg/ml for vancomycin, 1 and 2 μg/ml for levofloxacin, 0.03 and 16 μg/ml for penicillin G, 0.125 and 512 μg/ml for clindamycin, and 0.25 and 32 μg/ml for ceftriaxone. The P. acnes minimal biofilm eradication concentration (MBEC) was 16 μg/ml for rifampin; 32 μg/ml for penicillin G; 64 μg/ml for daptomycin and ceftriaxone; and ≥128 μg/ml for levofloxacin, vancomycin, and clindamycin. In the animal model, implants were infected by injection of 10⁹ CFU P. acnes in cages. Antimicrobial activity on P. acnes was investigated in the cage fluid (planktonic form) and on explanted cages (biofilm form). The cure rates were 4% for daptomycin, 17% for vancomycin, 0% for levofloxacin, and 36% for rifampin. Rifampin cured 63% of the infected cages in combination with daptomycin, 46% with vancomycin, and 25% with levofloxacin. While all tested antimicrobials showed good activity against planktonic P. acnes, for eradication of biofilms, rifampin was needed. In combination with rifampin, daptomycin showed higher cure rates than with vancomycin in this foreign-body infection model.
Topics: Animals; Anti-Bacterial Agents; Biofilms; Calorimetry; Foreign Bodies; Gram-Positive Bacterial Infections; Guinea Pigs; Male; Microbial Sensitivity Tests; Propionibacterium acnes; Rifampin
PubMed: 22252806
DOI: 10.1128/AAC.05552-11 -
Asia Pacific Journal of Clinical... 2006In this study we evaluated the ability of commercial strains (L. rhamnosus GG, L. rhamnosus LC705, and P. freudenreichii ssp. shermanii JS) in combination with B. breve... (Review)
Review
In this study we evaluated the ability of commercial strains (L. rhamnosus GG, L. rhamnosus LC705, and P. freudenreichii ssp. shermanii JS) in combination with B. breve 99 or B. lactis Bb12 to inhibit, displace and compete with model pathogens in order to test their influence on the adhesion of selected pathogens to immobilized human intestinal mucus. Our results demonstrate that specific probiotic combinations are able to enhance the inhibition percentages of pathogens adhesion to intestinal mucus when compared to individual strains. This suggests that combinations of probiotic strains are useful and more effective in inhibition of pathogen adhesion than individual strains. Such combinations should be assessed in clinical studies in subjects where the intestinal microbiota aberrancies have been identified.
Topics: Antibiosis; Bacterial Adhesion; Bifidobacterium; Humans; Intestinal Mucosa; Lactobacillus; Mucus; Probiotics; Propionibacterium
PubMed: 17077078
DOI: No ID Found -
Applied and Environmental Microbiology Sep 2006Autolysis is self-degradation of the bacterial cell wall that results in the release of enzymes and DNA. Autolysis of starter bacteria, such as lactococci and...
Autolysis is self-degradation of the bacterial cell wall that results in the release of enzymes and DNA. Autolysis of starter bacteria, such as lactococci and propionibacteria, is essential for cheese ripening, but our understanding of this important process is limited. This is mainly because the current tools for measuring autolysis cannot readily be used for analysis of bacteria in mixed populations. We have now addressed this problem by species-specific detection and quantification of free DNA released during autolysis. This was done by use of 16S rRNA gene single-nucleotide extension probes in combination with competitive PCR. We analyzed pure and mixed populations of Lactococcus lactis subsp. lactis and three different species of Propionibacterium. Results showed that L. lactis subsp. lactis INF L2 autolyzed first, followed by Propionibacterium acidipropionici ATCC 4965, Propionibacterium freudenreichii ISU P59, and then Propionibacterium jensenii INF P303. We also investigated the autolytic effect of rennet (commonly used in cheese production). We found that the effect was highly strain specific, with all the strains responding differently. Finally, autolysis of L. lactis subsp. lactis INF L2 and P. freudenreichii ISU P59 was analyzed in a liquid cheese model. Autolysis was detected later in this cheese model system than in broth media. A challenge with DNA, however, is DNA degradation. We addressed this challenge by using a DNA degradation marker. We obtained a good correlation between the degradation of the marker and the target in a model experiment. We conclude that our DNA approach will be a valuable tool for use in future analyses and for understanding autolysis in mixed bacterial populations.
Topics: Autolysis; Biomarkers; Cheese; Chymosin; DNA, Bacterial; Food Microbiology; Lactococcus; Polymerase Chain Reaction; Propionibacterium
PubMed: 16957244
DOI: 10.1128/AEM.00515-06 -
Scientific Reports Jan 2016Propionic acid (PA) is an important chemical building block widely used in the food, pharmaceutical, and chemical industries. In our previous study, a shuttle vector was...
Propionic acid (PA) is an important chemical building block widely used in the food, pharmaceutical, and chemical industries. In our previous study, a shuttle vector was developed as a useful tool for engineering Propionibacterium jensenii, and two key enzymes-glycerol dehydrogenase and malate dehydrogenase-were overexpressed to improve PA titer. Here, we aimed to improve PA production further via the pathway engineering of P. jensenii. First, the phosphoenolpyruvate carboxylase gene (ppc) from Klebsiella pneumoniae was overexpressed to access the one-step synthesis of oxaloacetate directly from phosphoenolpyruvate without pyruvate as intermediate. Next, genes encoding lactate dehydrogenase (ldh) and pyruvate oxidase (poxB) were deleted to block the synthesis of the by-products lactic acid and acetic acid, respectively. Overexpression of ppc and deleting ldh improved PA titer from 26.95 ± 1.21 g·L(-1) to 33.21 ± 1.92 g·L(-1) and 30.50 ± 1.63 g·L(-1), whereas poxB deletion decreased it. The influence of this pathway engineering on gene transcription, enzyme expression, NADH/NAD(+) ratio, and metabolite concentration was also investigated. Finally, PA production in P. jensenii with ppc overexpression as well as ldh deletion was investigated, which resulted in further increases in PA titer to 34.93 ± 2.99 g·L(-1) in a fed-batch culture.
Topics: Batch Cell Culture Techniques; Fermentation; Gene Deletion; Gene Expression; Intracellular Space; Metabolic Engineering; Metabolome; Metabolomics; NAD; Propionates; Propionibacterium
PubMed: 26814976
DOI: 10.1038/srep19963 -
The ISME Journal Sep 2015The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages...
The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium-phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey-predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy.
Topics: Acne Vulgaris; Bacteriophages; Base Sequence; Biodiversity; Clustered Regularly Interspaced Short Palindromic Repeats; Genome, Viral; Host-Pathogen Interactions; Humans; Metagenome; Microscopy, Electron; Phylogeny; Polymorphism, Single Nucleotide; Propionibacterium acnes; Skin
PubMed: 25848871
DOI: 10.1038/ismej.2015.47 -
Acta Orthopaedica Feb 2016Currently, Propionibacterium is frequently recognized as a causative microorganism of prosthetic joint infection (PJI). We assessed treatment success at 1- and 2-year... (Comparative Study)
Comparative Study
BACKGROUND AND PURPOSE
Currently, Propionibacterium is frequently recognized as a causative microorganism of prosthetic joint infection (PJI). We assessed treatment success at 1- and 2-year follow-up after treatment of Propionibacterium-associated PJI of the shoulder, hip, and knee. Furthermore, we attempted to determine whether postoperative treatment with rifampicin is favorable.
PATIENTS AND METHODS
We conducted a retrospective cohort study in which we included patients with a primary or revision joint arthroplasty of the shoulder, hip, or knee who were diagnosed with a Propionibacterium-associated PJI between November 2008 and February 2013 and who had been followed up for at least 1 year.
RESULTS
We identified 60 patients with a Propionibacterium-associated PJI with a median duration of 21 (0.1-49) months until the occurrence of treatment failure. 39 patients received rifampicin combination therapy, with a success rate of 93% (95% CI: 83-97) after 1 year and 86% (CI: 71-93) after 2 years. The success rate was similar in patients who were treated with rifampicin and those who were not.
INTERPRETATION
Propionibacterium-associated PJI treated with surgery in combination with long-term antibiotic administration had a successful outcome at 1- and 2-year follow-up irrespective of whether the patient was treated with rifampicin. Prospective studies are needed to determine whether the use of rifampicin is beneficial in the treatment of Propionibacterium-associated PJI.
Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cohort Studies; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Hip Prosthesis; Humans; Kaplan-Meier Estimate; Knee Prosthesis; Male; Middle Aged; Netherlands; Propionibacterium; Prosthesis Failure; Prosthesis-Related Infections; Reference Values; Reoperation; Retrospective Studies; Rifampin; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 26414972
DOI: 10.3109/17453674.2015.1094613 -
Infection and Immunity Oct 2015In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium...
Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro.
In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes.
Topics: Bacterial Proteins; Base Sequence; Biofilms; Carotid Arteries; Carotid Artery Diseases; Humans; Iron; Molecular Sequence Data; Norepinephrine; Peptide Hydrolases; Propionibacterium acnes
PubMed: 26216428
DOI: 10.1128/IAI.00510-15