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2.
J Med Chem ; 44(24): 4137-56, 2001 Nov 22.
Article in English | MEDLINE | ID: mdl-11708916

ABSTRACT

A novel series of erythromycin derivatives has been discovered with potent activity against key respiratory pathogens, including those resistant to erythromycin. These compounds are characterized by having an aryl group tethered to the C-6 position of the erythronolide skeleton. Extensive structural modification of the C-6 moiety led to the discovery of several promising compounds with potent activity against both mef- and erm-mediated resistant Streptoccoccus pneumoniae. Preliminary mechanistic studies indicated that the new macrolides are potent protein synthesis inhibitors, which interact with methylated ribosomes isolated from resistant organisms. In experimental animal models, these compounds exhibited excellent in vivo efficacy and balanced pharmacokinetic profiles.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Carbamates/chemical synthesis , Erythromycin/analogs & derivatives , Erythromycin/chemical synthesis , Ketolides , Protein Synthesis Inhibitors/chemical synthesis , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Carbamates/chemistry , Carbamates/pharmacology , Cell-Free System , Drug Resistance, Multiple , Erythromycin/chemistry , Erythromycin/pharmacology , Haemophilus influenzae/drug effects , Lung/microbiology , Mice , Models, Molecular , Protein Biosynthesis , Protein Synthesis Inhibitors/chemistry , Protein Synthesis Inhibitors/pharmacology , Rats , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Ribosomes/drug effects , Ribosomes/genetics , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/ultrastructure , Streptococcus pyogenes/drug effects , Structure-Activity Relationship , Transcription, Genetic
3.
Antimicrob Agents Chemother ; 45(9): 2585-93, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11502533

ABSTRACT

ABT-773 is a novel ketolide effective against antibacterial-resistant respiratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 microg/ml and an area under the concentration-time curve (AUC) of 12.03 microg. h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It concentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 based on the AUC. In acute systemic infections in mice, ABT-773 showed efficacy against macrolide-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin B-susceptible strain, an ermB strain, and an mefE strain. ABT-773 was also effective against Haemophilus influenzae lung infections in rats. Thus, ABT-773 may prove to be a useful new antibacterial agent for the treatment of respiratory tract infections.


Subject(s)
Bacterial Infections/drug therapy , Erythromycin/analogs & derivatives , Erythromycin/therapeutic use , Ketolides , Animals , Bacterial Infections/metabolism , Disease Models, Animal , Drug Resistance, Microbial , Erythromycin/pharmacokinetics , Female , Haemophilus Infections/drug therapy , Haemophilus Infections/metabolism , Haemophilus influenzae/drug effects , Listeriosis/drug therapy , Listeriosis/metabolism , Lung Diseases/drug therapy , Lung Diseases/metabolism , Lung Diseases/microbiology , Male , Mice , Rats , Rats, Sprague-Dawley , Respiratory Tract Diseases/drug therapy , Respiratory Tract Diseases/metabolism , Staphylococcal Infections/drug therapy , Staphylococcal Infections/metabolism , Streptococcal Infections/drug therapy , Streptococcal Infections/metabolism , Streptococcus pneumoniae/drug effects , Treatment Outcome
4.
Antimicrob Agents Chemother ; 45(7): 2163-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408246

ABSTRACT

The in vitro activities of ABT-773, erythromycin, clarithromycin, and azithromycin were compared. ABT-773 was the most active compound against macrolide-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Enterococcus spp. and multidrug-resistant Streptococcus pneumoniae. It also had good activity against gram-negative and atypical respiratory tract pathogens and Helicobacter pylori.


Subject(s)
Anti-Bacterial Agents/pharmacology , Erythromycin/analogs & derivatives , Erythromycin/pharmacology , Ketolides , Azithromycin/pharmacology , Clarithromycin/pharmacology , Drug Resistance, Multiple , Enterococcus/drug effects , Helicobacter pylori/drug effects , Humans , Microbial Sensitivity Tests , Staphylococcus/drug effects , Streptococcus/drug effects , Time Factors
5.
Bioorg Med Chem ; 8(7): 1677-96, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10976515

ABSTRACT

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.


Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Fungal Proteins , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/pharmacology , Peptides , Acute Disease , Amines/chemical synthesis , Amines/chemistry , Amines/pharmacology , Amphotericin B/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Candida/drug effects , Candidiasis, Vulvovaginal/drug therapy , Candidiasis, Vulvovaginal/microbiology , Disease Models, Animal , Dose-Response Relationship, Drug , Echinocandins , Female , Mice , Microbial Sensitivity Tests , Peptides, Cyclic/chemistry , Proline/chemistry , Solubility , Structure-Activity Relationship , Yeasts/drug effects
6.
Bioorg Med Chem Lett ; 10(13): 1405-8, 2000 Jul 03.
Article in English | MEDLINE | ID: mdl-10888319

ABSTRACT

Several 1,2,3,4-tetrahydro- and 7-N-hydroxycarbamate derivatives of the natural product rapamycin were prepared and assayed for their immunosuppressive and antifungal profiles. Substitutions at the 7-position indicate the possibility of a differentiated immunosuppressive to antifungal profile, whereas 40-position variants of the tetrahydro-analogues did not show similar differentiated activity.


Subject(s)
Antifungal Agents/pharmacology , Sirolimus/analogs & derivatives , Sirolimus/pharmacology , Animals , Antifungal Agents/chemistry , Biopharmaceutics , Candida/drug effects , Chemistry, Pharmaceutical , Humans , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Signal Transduction , Sirolimus/chemistry
7.
Bioorg Med Chem Lett ; 10(8): 815-9, 2000 Apr 17.
Article in English | MEDLINE | ID: mdl-10782693

ABSTRACT

A series of novel 6-O-substituted erythromycin A derivatives has been synthesized. Good in vitro antibacterial activity has been demonstrated for analogues incorporating a variety of structural features. The methodology disclosed is expected to find application in the design of future macrolide antibiotics that target the prevalent bacterial resistance problem.


Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Erythromycin/analogs & derivatives , Erythromycin/chemical synthesis , Erythromycin/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
8.
Antimicrob Agents Chemother ; 44(5): 1242-6, 2000 May.
Article in English | MEDLINE | ID: mdl-10770758

ABSTRACT

A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encountered Candida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition of Aspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Peptides, Cyclic/pharmacology , Antifungal Agents/chemistry , Microbial Sensitivity Tests , Peptides/pharmacology , Peptides, Cyclic/chemistry
10.
J Med Chem ; 42(20): 4202-13, 1999 Oct 07.
Article in English | MEDLINE | ID: mdl-10514290

ABSTRACT

The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MRSA. Preliminary studies indicated that oxoquinolizines possess distinct activity and toxicity profiles as compared with their parent quinolones. In order to develop a potent antibacterial agent with the desired spectrum of activity, good tolerability, and balanced pharmacokinetic profile, we synthesized and evaluated a series of oxoquinolizines with various substituents at the C-8 position. Most compounds tested in this study demonstrated better activity against Gram-positive bacteria than ciprofloxacin and exhibited good susceptibility against ciprofloxacin- and methicillin-resistant S. aureus. While maintaining potent in vitro activity, several compounds showed improved in vivo efficacy over ABT-719 as indicated by the mouse protection test. As an example, the oral ED(50) values for the cis-3-amino-4-methylpiperidine analogue 3ss against S. aureus NCTC 10649M, S. pneumoniae ATCC 6303, and E. coli JUHL were 0. 8, 2.0, and 1.4 mg/kg, compared to 3.0, 10.0, and 8.3 mg/kg for ABT-719. The current study revealed that the steric and electronic environment, conformation, and absolute stereochemistry of the C-8 group are very important to the antibacterial profiles. Structural modifications of the C-8 group provide a useful means to improve the antibacterial activities, physicochemical properties, and pharmacokinetic profiles. Manipulation of the C-8 group also allows us to generate analogues with the desired spectrum of activity, such as analogues that are selective against respiratory pathogens.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Quinolizines/chemical synthesis , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Mice , Quinolizines/chemistry , Quinolizines/pharmacology , Stereoisomerism , Structure-Activity Relationship
11.
Antimicrob Agents Chemother ; 42(9): 2385-90, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9736568

ABSTRACT

The dynamics of clarithromycin and azithromycin efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation. Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy. Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 microgram/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7. The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Clarithromycin/therapeutic use , Haemophilus Infections/drug therapy , Haemophilus influenzae , Lung Diseases/drug therapy , Animals , Azithromycin/pharmacokinetics , Clarithromycin/pharmacokinetics , Rats , Rats, Sprague-Dawley
12.
J Med Chem ; 41(10): 1651-9, 1998 May 07.
Article in English | MEDLINE | ID: mdl-9572890

ABSTRACT

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-susceptible Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, as well as improved activity compared to erythromycin A against the inducibly MLS (macrolide, lincosamide, and streptogramin B)-resistant organisms. Structure-activity studies revealed that arylalkyl carbamates with two and four carbon atoms between the aromatic moiety and carbamate nitrogen have the best in vitro activity. All of the C-10 epi analogues evaluated were found to have substantially less activity than the corresponding natural C-10 isomer. Several analogues demonstrated moderate antibacterial activity against the constitutively resistant S.aureus A-5278, S. pneumoniae5979, and S.pyogenes 930. However, despite potent in vitro activity, these analogues showed only moderate in vivo activity in mouse protection studies.


Subject(s)
Anti-Bacterial Agents , Carbamates , Erythromycin , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Carbamates/chemical synthesis , Carbamates/chemistry , Carbamates/pharmacology , Clarithromycin/chemistry , Clarithromycin/pharmacology , Colony Count, Microbial , Drug Evaluation, Preclinical , Drug Resistance, Microbial , Drug Resistance, Multiple , Erythromycin/analogs & derivatives , Erythromycin/chemical synthesis , Erythromycin/chemistry , Erythromycin/pharmacology , Haemophilus influenzae/drug effects , Lincosamides , Macrolides/pharmacology , Mice , Molecular Conformation , Pneumococcal Infections/prevention & control , Staphylococcal Infections/prevention & control , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects , Streptococcus pyogenes/drug effects , Structure-Activity Relationship , Virginiamycin/pharmacology
13.
J Med Chem ; 41(10): 1660-70, 1998 May 07.
Article in English | MEDLINE | ID: mdl-9572891

ABSTRACT

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.


Subject(s)
Anti-Bacterial Agents , Erythromycin/analogs & derivatives , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Clarithromycin/pharmacology , Drug Evaluation, Preclinical , Drug Resistance, Microbial , Drug Resistance, Multiple , Erythromycin/chemical synthesis , Erythromycin/chemistry , Erythromycin/pharmacology , Lincosamides , Macrolides/pharmacology , Mice , Pneumococcal Infections/prevention & control , Staphylococcal Infections/prevention & control , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects , Streptococcus pyogenes/drug effects , Structure-Activity Relationship , Virginiamycin/pharmacology
14.
J Clin Microbiol ; 35(6): 1311-5, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9163435

ABSTRACT

The National Committee for Clinical Laboratory Standards (NCCLS) methods for susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to be less susceptible to macrolides at lower pHs. Forty-four strains of H. influenzae were tested for their susceptibilities to clarithromycin and azithromycin by the disk diffusion and broth microdilution methods. The isolates appeared to be less susceptible at pH 7.2 than at pH 7.4 by both methods. Clarithromycin was less active at pH 7.2 against 43% of the isolates by the disk diffusion method and against 52% of the isolates by the broth microdilution method. Similarly, azithromycin was less active at pH 7.2 against 41 and 45% of the isolates by the disk diffusion and broth microdilution methods, respectively. Forty-two isolates were classified as clarithromycin susceptible and all isolates were classified as azithromycin susceptible by the disk diffusion method, regardless of the medium pH. However, only 21 isolates were clarithromycin susceptible at pH 7.2 and 34 isolates were susceptible at pH 7.4 by the broth microdilution method, even though quality control results indicated valid testing at both pHs. This study indicated that the results of tests of the susceptibility of H. influenzae with clarithromycin and azithromycin are highly dependent on the pH of the medium. Test results and their interpretations varied even when the medium pH was within the NCCLS-approved range and, coupled with the current NCCLS breakpoint of 8 microg/ml in the case of clarithromycin, may explain some of the observed discordances between the disk diffusion and broth microdilution methods.


Subject(s)
Anti-Bacterial Agents/pharmacology , Azithromycin/pharmacology , Clarithromycin/pharmacology , Haemophilus influenzae/drug effects , Microbial Sensitivity Tests/standards , Hydrogen-Ion Concentration , Microbial Sensitivity Tests/methods
15.
J Antibiot (Tokyo) ; 49(5): 465-77, 1996 May.
Article in English | MEDLINE | ID: mdl-8682724

ABSTRACT

The 11,12-cyclic carbazate of 3-keto-6-O-methylerythromycin A (4) was prepared. This compound shows in vitro antibacterial activity comparable to erythromycin A (1) against erythromycin-susceptible organisms and increased activity against some erythromycin-resistant organisms. Using 4 as a lead, a series of analogues was prepared by acylation or alkylation of the carbazate nitrogen. Several of the N-alkylated derivatives showed dramatically improved antibacterial activity against both susceptible and resistant organisms as compared to erythromycin A.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Erythromycin/pharmacology , Ketolides , Anti-Bacterial Agents/chemistry , Erythromycin/analogs & derivatives , Erythromycin/chemical synthesis , Erythromycin/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
16.
J Dent Res ; 72(6): 1027-31, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8388413

ABSTRACT

Cell-free culture filtrates of Porphyromonas gingivalis grown in Wilkins-Chalgren broth stimulated the growth of six strains of Treponema denticola in 1186 broth when compared with the effect of uninoculated WC. The pH of the 1186 broth was not altered by the addition of either culture filtrate or WC, and all media were fully reduced prior to inoculation with T. denticola. Growth was also stimulated by factors precipitated from the culture filtrate with 90% (NH4)2SO4, 50% cold ethanol, or 50% cold acetone, and by factors retained after dialysis of the culture filtrate through a membrane with a molecular weight cut-off of 50 kDa. Growth factor activity was eliminated by heating of the culture filtrate at 55 degrees C for 4 h. An ether extract of the culture filtrate containing acetic, butyric, isobutyric, isovaleric, propionic, and phenylacetic acids did not stimulate growth. Since subgingival plaque from periodontal pockets colonized with T. denticola also contains P. gingivalis, certain extracellular proteins with molecular weights greater than 50 kDa produced by P. gingivalis may act as growth factors for T. denticola in the microenvironment of the periodontal pocket.


Subject(s)
Bacterial Proteins/pharmacology , Growth Substances/chemistry , Porphyromonas gingivalis/chemistry , Treponema/drug effects , Bacterial Proteins/analysis , Culture Media , Electrophoresis, Polyacrylamide Gel , Growth Substances/analysis , Growth Substances/pharmacology , Molecular Weight , Symbiosis , Treponema/growth & development
17.
J Periodontol ; 63(2): 131-6, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1372653

ABSTRACT

The purpose of this study was to use monoclonal antibodies to enumerate spirochetes in dental plaque, including the newly recognized pathogen-related oral spirochete (PROS) and specific serovars of Treponema denticola. Plaque was collected from control subjects with no apparent periodontal disease and from sites of moderate to severe chronic periodontitis in patients with inflammatory periodontal disease. Individual monoclonal antibodies were used to determine whether spirochetes were present and then a double-staining protocol was employed to count total spirochetes and specific treponemes in individual microscopic fields. Results indicate that spirochetes are more common at diseased sites and in subgingival plaque than at healthy sites or in supragingival plaque. Together PROS and T. denticola comprised the majority of all spirochetes in all samples and PROS and T. denticola serovars "B" and D were most numerous in plaque from patients with periodontitis. PROS were the majority of all spirochetes in supragingival plaque (76.2% +/- 23.8%) and subgingival plaque (60.9% +/- 19.1%) from periodontitis patients, significantly larger than the percentage of T. denticola serovar "B" (P less than .001 for both supragingival and subgingival plaque) and serovar D (P less than .01 for supragingival and P less than .001 for subgingival plaque). These observations indicate that PROS are the predominant spirochete in plaque from sites of patients with periodontitis, but other analytical approaches are necessary to determine if PROS or T. denticola are pathogenic.


Subject(s)
Dental Plaque/microbiology , Periodontitis/microbiology , Spirochaetales/isolation & purification , Treponema/isolation & purification , Adult , Antibodies, Monoclonal , Bacterial Typing Techniques , Colony Count, Microbial , Female , Humans , Male , Middle Aged , Periodontium/microbiology , Spirochaetales/classification , Staining and Labeling , Treponema/classification
20.
J Med Vet Mycol ; 28(5): 395-403, 1990.
Article in English | MEDLINE | ID: mdl-2149385

ABSTRACT

Clinical and environmental isolates of Aspergillus fumigatus synthesized extracellular siderophores when grown in defined medium. Six hydroxamate siderophores were purified from culture filtrates and identified by thin layer chromatography. The most prominent siderophore was identified as N,N',N"-triacetylfusarinine C and the second most prominent siderophore was identified as ferricrocin. In addition, a hydrolytic product of N,N',N"-triacetylfusarinine C was identified. Three other siderophores were present in smaller amounts and were not identified. Since the same siderophores were produced by isolates from diseases of varying severity and from environmental material, it is unlikely that the extracellular siderophores function as virulence factors during infection. However, they may function as growth factors by mediating iron uptake by the fungus in the micro-environment of the inflammatory focus.


Subject(s)
Aspergillus fumigatus/analysis , Ionophores/analysis , Iron Chelating Agents/analysis , Aspergillus fumigatus/growth & development , Aspergillus fumigatus/pathogenicity , Chromatography, Thin Layer , Culture Media , Ionophores/isolation & purification , Iron Chelating Agents/isolation & purification , Siderophores
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