Increase in the in vitro susceptibility of Staphylococcus aureus to antimicrobial agents in the presence of Candida albicans

1979 ◽  
Vol 25 (4) ◽  
pp. 429-435 ◽  
Author(s):  
J. deRepentigny ◽  
R. Lévesque ◽  
L. G. Mathieu
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Candida Albicans ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Mixed Cultures ◽  
Alpha Toxin ◽  
In Vitro Susceptibility ◽  
Pure Cultures

In experiments with mixed cultures of Staphylococcus aureus and Candida albicans both in the absence and in the presence of 5-fluorocytosine (5-FC), we have observed that (1) there is an inhibition of S. aureus growth in mixed cultures with C. albicans in media supplemented with 1 μg/mL of 5-FC and that 5-FC has no effect on staphylococci in pure cultures; (2) this inhibition occurred with clinically isolated and laboratory strains and could be reversed by specific metabolites; (3) Staphylococcus aureus was inhibited by filtrates of C. albicans cultures treated with 5-FC and this seemed to be favored by some C. albicans filterable product which can affect the cell wall and the permeability of the staphylococcal cells since they become sensitive to 5-FC; (4) nine other commonly used antimicrobials showed an increased inhibitory activity against S. aureus in mixed cultures with C. albicans; and (5) there is a decrease in the number of precipitating antigens of S. aureus and of the activity of alpha toxin when this species was grown with both C. albicans and 5-FC. Our results indicate that the susceptibility of some species to antimicrobials could be significantly modified in the presence of other species. One cannot exclude that a similar phenomenon could happen in hosts under treatment with antibiotics against infection.

scholarly journals Candida albicans Impacts Staphylococcus aureus Alpha-Toxin Production via Extracellular Alkalinization

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Olivia A. Todd ◽  
Mairi C. Noverr ◽  
Brian M. Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Extracellular Ph ◽  
Morbidity And Mortality ◽  
Alpha Toxin ◽  
Content Type

ABSTRACT Candida albicans and Staphylococcus aureus are common causes of nosocomial infections with severe morbidity and mortality. Murine polymicrobial intra-abdominal infection (IAI) with C. albicans and S. aureus results in acute mortality dependent on the secreted cytolytic effector alpha-toxin. Here, we confirmed that alpha-toxin is elevated during polymicrobial growth compared to monomicrobial growth in vitro. Therefore, this study sought to unravel the mechanism by which C. albicans drives enhanced staphylococcal alpha-toxin production. Using a combination of functional and genetic approaches, we determined that an intact agr quorum sensing regulon is necessary for enhanced alpha-toxin production during coculture and that a secreted candidal factor likely is not implicated in elevating agr activation. As the agr system is pH sensitive, we observed that C. albicans raises the pH during polymicrobial growth and that this correlates with increased agr activity and alpha-toxin production. Modulation of the pH could predictably attenuate or activate agr activity during coculture. By using a C. albicans mutant deficient in alkalinization (stp2Δ/Δ), we confirmed that modulation of the extracellular pH by C. albicans can drive agr expression and toxin production. Additionally, the use of various Candida species (C. glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, and C. krusei) demonstrated that those capable of raising the extracellular pH correlated with elevated agr activity and alpha-toxin production during coculture. Overall, we demonstrate that alkalinization of the extracellular pH by the Candida species leads to sustained activation of the staphylococcal agr system. IMPORTANCE Candida albicans and Staphylococcus aureus are commonly coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Thus, they represent a significant cause of nosocomial morbidity and mortality. Yet how these organisms behave in the context of polymicrobial growth remains poorly understood. In this work, we set out to determine the mechanism by which activation of the staphylococcal agr quorum sensing system and production of its major virulence effector alpha-toxin is enhanced during coculture with C. albicans. Surprisingly, we likely ruled out that a secreted candidal factor drives this process. Instead, we demonstrated that alkalinization of the extracellular milieu by C. albicans and other Candida species correlated with elevated agr activity. Thus, we propose a mechanism where modulation of the extracellular pH by fungal opportunists can indirectly alter virulence of a bacterial pathogen. Uncovering molecular events that drive interkingdom pathogenicity mechanisms may enhance surveillance and treatment for devastating polymicrobial infections.

scholarly journals In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis.

1996 ◽  
Vol 40 (3) ◽  
pp. 799-801 ◽  
Author(s):  
G W Kaatz ◽  
S M Seo
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Clinical Strains ◽  
Time Kill

The new oxazolidinone antimicrobial agents U100592 and U100766 demonstrated good in vitro inhibitory activity against clinical strains of Staphylococcus aureus and Staphylococcus epidermidis regardless of methicillin susceptibility. Both agents appeared bacteriostatic by time-kill analysis. Stable resistance to low multiples of the MIC of either drug could be produced only in methicillin-resistant S. aureus.

scholarly journals Effect of fluconazole on viability of Candida albicans over extended periods of time.

1996 ◽  
Vol 40 (11) ◽  
pp. 2622-2625 ◽  
Author(s):  
P G Sohnle ◽  
B L Hahn ◽  
M D Erdmann
Keyword(s):  
Candida Albicans ◽  
Marked Reduction ◽  
Culture Medium ◽  
Antimicrobial Agents ◽  
Yeast Cells ◽  
In Vitro Susceptibility ◽  
Fungistatic Activity ◽  
Susceptibility Tests ◽  
Infecting Organisms

The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time. It is possible that an azole antifungal drug such as fluconazole, with primarily fungistatic activity in standard in vitro susceptibility tests, might be able to damage the fungal cells and reduce their viability over prolonged incubations under nonproliferating conditions. To test this possibility, Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degrees C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times during this period revealed no increased loss of viability for the fluconazole-exposed organisms. However, when fluconazole was added to the organisms maintained in distilled water (with or without pretreatment with the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were found for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 microgram of fluconazole per ml versus 0 of 10 and 1 of 11 control samples (P of < 0.01 and 0.001, respectively). The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C rather than 25 degrees C. These findings suggest that fluconazole may have fungicidal effects on fungal cells during prolonged exposures under conditions in which the organisms are prevented from proliferating by lack of nutrients.

scholarly journals Ceftaroline Increases Membrane Binding and Enhances the Activity of Daptomycin against Daptomycin-Nonsusceptible Vancomycin-Intermediate Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

2012 ◽  
Vol 57 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Brian J. Werth ◽  
George Sakoulas ◽  
Warren E. Rose ◽  
Joseph Pogliano ◽  
Ryan Tewhey ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Wall Thickness ◽  
Antimicrobial Agents ◽  
Single Agent ◽  
Pharmacodynamic Model ◽  
Cell Wall Thickness ◽  
Ceftaroline Fosamil ◽  
Content Type

ABSTRACTNew antimicrobial agents and novel combination therapies are needed to treat serious infections caused by methicillin-resistantStaphylococcus aureus(MRSA) with reduced susceptibility to daptomycin and vancomycin. The purpose of this study was to evaluate the combination of ceftaroline plus daptomycin or vancomycin in anin vitropharmacokinetic/pharmacodynamic model. Simulations of ceftaroline-fosamil at 600 mg per kg of body weight every 8 h (q8h) (maximum free-drug concentration in serum [fCmax], 15.2 mg/liter; half-life [t1/2], 2.3 h), daptomycin at 10 mg/kg/day (fCmax, 11.3 mg/liter;t1/2, 8 h), vancomycin at 2 g q12h (fCmax, 30 mg/liter;t1/2, 6 h), ceftaroline plus daptomycin, and ceftaroline plus vancomycin were evaluated against a clinical, isogenic MRSA strain pair: D592 (daptomycin susceptible and heterogeneous vancomycin intermediate) and D712 (daptomycin nonsusceptible and vancomycin intermediate) in a one-compartmentin vitropharmacokinetic/pharmacodynamic model over 96 h. Therapeutic enhancement of combinations was defined as ≥2 log10CFU/ml reduction over the most active single agent. The effect of ceftaroline on the membrane charge, cell wall thickness, susceptibility to killing by the human cathelicidin LL37, and daptomycin binding were evaluated. Therapeutic enhancement was observed with daptomycin plus ceftaroline in both strains and vancomycin plus ceftaroline against D592. Ceftaroline exposure enhanced daptomycin-induced depolarization (81.7% versus 72.3%;P= 0.03) and killing by cathelicidin LL37 (P< 0.01) and reduced cell wall thickness (P< 0.001). Fluorescence-labeled daptomycin was bound over 7-fold more in ceftaroline-exposed cells. Whole-genome sequencing and mutation analysis of these strains indicated that change in daptomycin susceptibility is related to anfmtC(mprF) mutation. The combination of daptomycin plus ceftaroline appears to be potent, with rapid and sustained bactericidal activity against both daptomycin-susceptible and -nonsusceptible strains of MRSA.

Increased in vitro sensitivity of Candida albicans to amphotericin B when grown in mixed culture with Escherichia coli

1978 ◽  
Vol 24 (12) ◽  
pp. 1482-1489 ◽  
Author(s):  
L. G. Mathieu ◽  
D. Dube ◽  
M. Lebrun
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Mixed Culture ◽  
Mixed Cultures ◽  
Polyene Antibiotics ◽  
E Coli ◽  
Pure Cultures

The growth of Candida albicans was inhibited by some Escherichia coli strains both in conventional batch cultures and also in a chemostat under conditions of constant addition of fresh medium. Concentrations of 0.2 μg amphotericin B per millilitre and of 2 μg nystatin per millilitre, which caused a slight inhibition of C. albicans in pure culture, exerted a strong fungicidal effect when the yeast was placed in mixed cultures with certain strains of E. coli. Candida albicans cells, inhibited by either E. coli or in mixed culture with polyene antibiotics, appeared larger and less uniformly stained by acridine orange than control cells from pure cultures. Addition of chloramphenicol to the mixed cultures, in quantities sufficient to kill the E. coli cells, abolished the increased sensitivity of C. albicans to amphotericin B or nystatin. In preliminary in vivo tests, E. coli did not sensitize C. albicans to the polyene antibiotics.

Interactions entre Staphylococcus aureus et Pseudomonas aeruginosa dans des cultures in vitro et au cours d'infections expérimentales

1972 ◽  
Vol 18 (10) ◽  
pp. 1531-1541 ◽  
Author(s):  
J. de Repentigny ◽  
L. G. Mathieu ◽  
T. Gadbois
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Pure Culture ◽  
Maximum Growth ◽  
Mixed Cultures ◽  
Mixed Infections ◽  
Alpha Toxin ◽  
Culture Supernatants

Staphylococcus aureus and Pseudomonas aeruginosa are often found in succession or in association in infections. To study experimentally their interactions, we have used systems of growth or survival of mixed cultures of both species in vitro in a semisynthetic medium and in vivo in the peritoneal cavity of mice. Conditions for maximum growth in vitro of both species in mixed cultures are about similar to those in pure culture when the pH is maintained between 6.0 and 7.3. The inhibition of S. aureus growth by some antimetabolites or antibiotics, e.g., 5-methyltryptophan and D-cycloserine, is antagonized in mixed cultures. Staphylococcus coagulase, DNase, and alpha toxin were present either in mixed cultures or after mixing pure culture supernatants of both species, but P. aeruginosa slime was not observed in these conditions. In vivo, the survival of S. aureus seemed greater in mixed infections with P. aeruginosa than in those with S. aureus alone. In our systems, S. aureus may have benefited from the presence of P. aeruginosa whereas the reverse was not observed. These observations on interbacterial ecology could help to explain the importance and the behavior of some species at the initiation of pyogenic infections, either their interactions or their selection.

scholarly journals Phenolic Plant Extracts Versus Penicillin G: In Vitro Susceptibility of Staphylococcus aureus Isolated from Bovine Mastitis

2019 ◽  
Vol 12 (3) ◽  
pp. 128
Author(s):  
Fernanda Gomes ◽  
Maria Rodrigues ◽  
Natália Martins ◽  
Isabel Ferreira ◽  
Mariana Henriques
Keyword(s):  
Staphylococcus Aureus ◽  
Plant Extracts ◽  
Antimicrobial Agents ◽  
Juglans Regia ◽  
Bovine Mastitis ◽  
Treatment Plant ◽  
The Other ◽  
Penicillin G ◽  
In Vitro Susceptibility

Antibiotics are the elective drugs in bovine mastitis (BM) treatment, despite their low rates of efficiency and effectiveness and increasing risk of pathogen resistance. In this sense, it is urgent to discover new and effective antimicrobial agents to apply in BM control and even treatment. Plant extracts have been widely recognized as a rich source of phytochemicals with antimicrobial potential. Thus, the present work aims to compare the bioactivity of Eucalyptus globulus and Juglans regia extracts against Staphylococcus aureus bovine mastitis strains with penicillin G. At non-toxic concentrations, E. globulus exerted a bacteriostatic effect in planktonic cells and J. regia had no antimicrobial activity. Penicillin G, at minimum inhibitory concentration (MIC), demonstrated bactericidal activity, but just for S. aureus 3, 5, 6 and ATCC 25923, while the other strains seem to have acquired resistance. On the other hand, E. globulus and penicillin G in combination demonstrated synergy, being the most effective approach against S. aureus 1, 2 and 4. Thus, penicillin alone and in combination with E. globulus or J. regia seems to be promissory strategies to control bovine mastitis infections.

Sensitivity of Staphylococcus Aureus, Isolated from Skin Infections in 1994, to 19 Antimicrobial Agents

1995 ◽  
Vol 23 (5) ◽  
pp. 328-334 ◽  
Author(s):  
S Nishijima ◽  
M Nakagawa ◽  
T Sugiyama ◽  
H Akamatsu ◽  
T Horio ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Antimicrobial Agents ◽  
Skin Infections ◽  
In Vitro Susceptibility ◽  
Methicillin Resistant ◽  
Cefpodoxime Proxetil ◽  
Agar Dilution ◽  
Resistant Strains

The most common pathogen causing skin infections is Staphylococcus aureus and the incidence of multiply resistant strains of S. aureus has been increasing. The in vitro susceptibility of 130 isolates of S. aureus to 19 antimicrobial agents: ampicillin (ABPC), methicillin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, nadifloxacin and grepafloxacin, was evaluated by agar dilution tests. The S. aureus isolates were isolated from 130 patients with skin infections in 1994. The proportion of methicillin-resistant S. aureus isolates among the strains isolated was 19.2%. The concentration needed to inhibit 50% of the isolates was 3.13 mg/ml or less for all of the drugs, but the concentration needed to inhibit 90% of isolates was over 12.5 μg/ml, except in the cases of minocycline, vancomycin, fusidic acid, tosufloxacin and nadifloxacin. Tosufloxacin and nadifloxacin had the lowest minimum inhibitory concentrations. None of the S. aureus strains was resistant to nadifloxacin.

scholarly journals In Vitro Antimicrobial Activity of Aqueous-Methanolic Extract of Populus sp. Leaves

2019 ◽  
Vol 31 (2) ◽  
pp. 53-64
Author(s):  
Husein A. Husein ◽  
Dhurgham A.H. Alhasan ◽  
Majid A.Z. Albadry
Keyword(s):  
Amino Acids ◽  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Streptococcus Mutans ◽  
Antimicrobial Agents ◽  
Methanolic Extract ◽  
Inhibition Zone ◽  
Microbial Pathogens

Plants are a rich source of giving benefit natural products, including antimicrobial agents. The current study was designed to evaluate the antimicrobial activity of Populus sp. leaves that the aqueous methanolic extract (200 mg.ml-1) of the leaves revealed antimicrobial effects against some microbial pathogens in which the highest inhibition zone was recorded against Candida albicans followed by Staphylococcus aureus but no effects on the growth of both Streptococcus mutans and Klebsiella sp. The chemical tests appeared that the extract contains sterols, terpenoids, carbohydrates, glycosides, flavonoids, tannins, proteins, amino acids, and saponins glycosides while alkaloids were not detected. GC-MS analysis detected the aqueous methanolic extract has four compounds are {2-Pyridineacetaldehyde,[2-(2-pyridinyl) ethylidene]hydrazone}, {n-Propylamine, N-acetyl-3-[2-acetyl-3,4,5-trimethoxyphenyl]-},{1-(Methyl propyl)-4-(1’,1’,2’-trichloro-3’-ethyl allyl)benzene} and {1H-Indole, 5- methyl-2-phenyl-}.

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