RESUMEN
A targeted metabologenomic method was developed to selectively discover terminal oxazole-bearing natural products from bacteria. For this, genes encoding oxazole cyclase, a key enzyme in terminal oxazole biosynthesis, were chosen as the genomic signature to screen bacterial strains that may produce oxazole-bearing compounds. Sixteen strains were identified from the screening of a bacterial DNA library (1,000â strains) using oxazole cyclase gene-targeting polymerase chain reaction (PCR) primers. The PCR amplicon sequences were subjected to phylogenetic analysis and classified into nine clades. 1H-13C coupled-HSQC NMR spectra obtained from the culture extracts of the hit strains enabled the unequivocal detection of the target compounds, including five new oxazole compounds, based on the unique 1JCH values and chemical shifts of oxazole: lenzioxazole (1) possessing an unprecedented cyclopentane, permafroxazole (2) bearing a tetraene conjugated with carboxylic acid, tenebriazine (3) incorporating two modified amino acids, and methyl-oxazolomycins A and B (4 and 5). Tenebriazine displayed inhibitory activity against pathogenic fungi, whereas methyl-oxazolomycins A and B (4 and 5) selectively showed anti-proliferative activity against estrogen receptor-positive breast cancer cells. This metabologenomic method enables the logical and efficient discovery of new microbial natural products with a target structural motif without the need for isotopic labeling.
Asunto(s)
Productos Biológicos , Oxazoles , Oxazoles/química , Oxazoles/farmacología , Oxazoles/metabolismo , Productos Biológicos/química , Productos Biológicos/farmacología , Productos Biológicos/metabolismo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Metabolómica , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Bacterias/efectos de los fármacosRESUMEN
Two nitrogenous metabolites, bacillimide (1) and bacillapyrrole (2), were isolated from the culture broth of the marine-derived actinomycete Streptomyces bacillaris. Based on the results of combined spectroscopic and chemical analyses, the structure of bacillimide (1) was determined to be a new cyclopenta[c]pyrrole-1,3-dione bearing a methylsulfide group, while the previously reported bacillapyrrole (2) was fully characterized for the first time as a pyrrole-carboxamide bearing an alkyl sulfoxide side chain. Bacillimide (1) and bacillapyrrole (2) exerted moderate (IC50 = 44.24 µM) and weak (IC50 = 190.45 µM) inhibitory effects on Candida albicans isocitrate lyase, respectively. Based on the growth phenotype using icl-deletion mutants and icl expression analyses, we determined that bacillimide (1) inhibits the transcriptional level of icl in C. albicans under C2-carbon-utilizing conditions.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Isocitratoliasa/efectos de los fármacos , Streptomyces/metabolismo , Antifúngicos/aislamiento & purificación , Candida albicans/enzimología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Nitrógeno/metabolismoRESUMEN
Four epipolythiodioxopiperazine fungal metabolites (1-4) isolated from the sponge-derived Aspergillus quadrilineatus FJJ093 were evaluated for their capacity to inhibit isocitrate lyase (ICL) in the glyoxylate cycle of Candida albicans. The structures of these compounds were elucidated using spectroscopic techniques and comparisons with previously reported data. We found secoemestrin C (1) (an epitetrathiodioxopiperazine derivative) to be a potent ICL inhibitor, with an inhibitory concentration of 4.77 ± 0.08 µM. Phenotypic analyses of ICL-deletion mutants via growth assays with acetate as the sole carbon source demonstrated that secoemestrin C (1) inhibited C. albicans ICL. Semi-quantitative reverse-transcription polymerase chain reaction analyses indicated that secoemestrin C (1) inhibits ICL mRNA expression in C. albicans under C2-assimilating conditions.
Asunto(s)
Candida albicans/efectos de los fármacos , Proteínas Fúngicas/antagonistas & inhibidores , Isocitratoliasa/antagonistas & inhibidores , Piperazinas/farmacología , Aspergillus/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Glioxilatos/metabolismo , Isocitratoliasa/química , Isocitratoliasa/genética , Piperazinas/química , Piperazinas/metabolismo , Proteínas Recombinantes/químicaRESUMEN
Thirteen coumarins (1-13), including five new compounds (1-5), were isolated from the folk medicinal plant Poncirus trifoliata. Combined spectroscopic analyses revealed that coumarins 1-4 are bis-isoprenylated coumarins with diverse oxidation patterns, while 5 is an enantiomeric di-isoprenylated coumarin. The absolute configurations of the stereogenic centers in the isoprenyl chains were assigned through MTPA and MPA methods, and those of the known compounds triphasiol (6) and ponciol (7) were also assigned using similar methods. These coumarins inhibited significantly Staphylococcus aureus-derived sortase A (SrtA), a transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall in Gram-positive bacteria. The present results obtained indicated that the bioactivity and underlying mechanism of action of these coumarins are associated with the inhibition of SrtA-mediated S. aureus adhesion to eukaryotic cell matrix proteins including fibrinogen and fibronectin, thus potentially serving as SrtA inhibitors.
Asunto(s)
Aminoaciltransferasas/antagonistas & inhibidores , Proteínas Bacterianas/antagonistas & inhibidores , Cumarinas/farmacología , Plantas Medicinales , Poncirus , Cisteína Endopeptidasas , Fibrinógeno , Fibronectinas , Bacterias Grampositivas , Proteínas de la Membrana , Estructura Molecular , Infecciones Estafilocócicas , Staphylococcus aureusRESUMEN
The cultivation of a Streptomyces sp. SD53 strain isolated from the gut of the silkworm Bombyx mori produced two macrolactam natural products, piceamycin (1) and bombyxamycin C (2). The planar structures of 1 and 2 were identified by a combination of NMR, MS, and UV spectroscopic analyses. The absolute configurations were assigned based on chemical and chromatographic methods as well as ECD calculations. A new chromatography-based experimental method for determining the configurations of stereogenic centers ß to nitrogen atoms in macrolactams was established and successfully applied in this report. These compounds exhibited significant bioactivities against the silkworm entomopathogen Bacillus thuringiensis and various human pathogens as well as human cancer cell lines. In particular, piceamycin potently inhibited Salmonella enterica and Proteus hauseri with MIC values of 0.083 µg/mL and 0.025 µg/mL, respectively. The biosynthetic pathway involved in the formation of the cyclopentenone moiety in piceamycin is discussed.
Asunto(s)
Antibacterianos/farmacología , Productos Biológicos/química , Lactamas Macrocíclicas/química , Streptomyces/química , Antibacterianos/química , Productos Biológicos/metabolismo , Vías Biosintéticas , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Proteus/química , EstereoisomerismoRESUMEN
This study aims to isolate and identify the structure of antibacterial compounds having potent activity on methicillin-resistant Staphylococcus aureus (MRSA) from marine actinomycetes, and also to identify their mode of action. Lactoquinomycin A (LQM-A) (compound 1) and its derivatives (2-4) were isolated from marine-derived Streptomyces bacillaris strain MBTC38, and their structures were determined using extensive spectroscopic methods. These compounds showed potent antibacterial activities against Gram-positive bacteria, with MIC values of 0.06-4 µg/mL. However, the tested compounds exhibited weak inhibitory activity against Gram-negative bacteria, although they were effective against Salmonella enterica (MIC = 0.03-1 µg/mL). LQM-A exhibited the most significant inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC = 0.25-0.5 µg/mL), with a low incidence of resistance. An in vivo dual-reporter assay designed to distinguish between compounds that inhibit translation and those that induce DNA damage was employed to assess the mode of action of LQM-A. LQM-A-induced DNA damage and did not inhibit protein synthesis. The gel mobility shift assay showed that LQM-A switched plasmid DNA from the supercoiled to relaxed form in a time- and concentration-dependent manner. These data suggest that LQM-A intercalated into double-stranded DNA and damaged DNA repair.
Asunto(s)
Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Streptomyces/metabolismo , Antibacterianos/aislamiento & purificación , Daño del ADN , ADN Bacteriano/genética , Cinética , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftoquinonas/aislamiento & purificación , Naftoquinonas/farmacología , Conformación de Ácido Nucleico , Relación Estructura-ActividadRESUMEN
A marine-derived actinomycete (Streptomyces sp. MBTI36) exhibiting antibacterial activities was investigated in the present study. The strain was identified using genetic techniques. The 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces microflavus. Furthermore, a new chromomycin A9 (1), along with chromomycin Ap (2), chromomycin A2 (3), and chromomycin A3 (4), were isolated from the ethyl acetate extract. Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, and HRMS, as well as comparisons with previously reported data. Compounds 1-4 showed potent antibacterial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). During a passage experiment, minimum inhibitory concentration (MIC) values for compounds 1-4 showed no more than a 4-fold increase from the starting MIC value, indicating that no resistance was detected over the 21 passages.
Asunto(s)
Antibacterianos/farmacología , Cromomicinas/farmacología , Streptomyces/química , Streptomyces/metabolismo , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Organismos Acuáticos/química , Organismos Acuáticos/clasificación , Organismos Acuáticos/genética , Organismos Acuáticos/metabolismo , Cromomicinas/química , Cromomicinas/aislamiento & purificación , Farmacorresistencia Bacteriana , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 16S/genética , Streptomyces/clasificación , Streptomyces/genéticaRESUMEN
Seven alkaloidal compounds (2-8) and one polyketide (1) were isolated from a semisolid rice culture of the marine-derived fungus Aspergillus sp. F452. Structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported data. The alkaloidal compounds (2-8) displayed weak to moderate inhibitory activities against Staphylococcus aureus-derived sortase A (SrtA) without affecting cell viability. Aspermytin A (1) strongly inhibited SrtA activity, with an IC50 value of 146.0 µM, and significantly reduced bacterial adherence to fibronectin-coated surfaces. The present results indicate that the underlying mechanism of action of compound 1 is associated with the inhibition of SrtA-mediated S. aureus adhesion to fibronectin, thus potentially serving as an SrtA inhibitor.
Asunto(s)
Alcaloides/farmacología , Aminoaciltransferasas/antagonistas & inhibidores , Antibacterianos/farmacología , Aspergillus/metabolismo , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Staphylococcus aureus/efectos de los fármacos , Alcaloides/aislamiento & purificación , Aminoaciltransferasas/metabolismo , Antibacterianos/aislamiento & purificación , Adhesión Bacteriana/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Línea Celular Tumoral , Cisteína Endopeptidasas/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Fibronectinas/metabolismo , Humanos , Cinética , Estructura Molecular , Staphylococcus aureus/enzimología , Relación Estructura-ActividadRESUMEN
Six new bis(indole) alkaloids (1-6) along with eight known ones of the topsentin class were isolated from a Spongosorites sp. sponge of Korea. Based on the results of combined spectroscopic analyses, the structures of spongosoritins A-D (1-4) were determined to possess a 2-methoxy-1-imidazole-5-one core connecting the indole moieties, and these were linked by a linear urea bridge for spongocarbamides A (5) and B (6). The absolute configurations of spongosoritins were assigned by electronic circular dichroism (ECD) computation. The new compounds exhibited moderate inhibition against transpeptidase sortase A and weak inhibition against human pathogenic bacteria and A549 and K562 cancer cell lines.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Alcaloides Indólicos/farmacología , Poríferos/metabolismo , Células A549 , Aminoaciltransferasas/antagonistas & inhibidores , Aminoaciltransferasas/metabolismo , Animales , Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/enzimología , Bacterias/crecimiento & desarrollo , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Supervivencia Celular/efectos de los fármacos , Cisteína Endopeptidasas/metabolismo , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Humanos , Alcaloides Indólicos/aislamiento & purificación , Células K562 , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Relación Estructura-ActividadRESUMEN
Chemical profiling of the Streptomyces sp. strain SUD119, which was isolated from a marine sediment sample collected from a volcanic island in Korea, led to the discovery of three new metabolites: donghaecyclinones A-C (1-3). The structures of 1-3 were found to be rearranged, multicyclic, angucyclinone-class compounds according to nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses. The configurations of their stereogenic centers were successfully assigned using a combination of quantum mechanics-based computational methods for calculating the NMR shielding tensor (DP4 and CP3) as well as electronic circular dichroism (ECD) along with a modified version of Mosher's method. Donghaecyclinones A-C (1-3) displayed cytotoxicity against diverse human cancer cell lines (IC50: 6.7-9.6 µM for 3).
Asunto(s)
Antraquinonas/química , Antraquinonas/farmacología , Sedimentos Geológicos/microbiología , Streptomyces/química , Antraquinonas/aislamiento & purificación , Antibacterianos , Antifúngicos , Antineoplásicos , Dicroismo Circular , Humanos , Islas , Estructura Molecular , República de CoreaRESUMEN
Four 2-alkyl-4-hydroxyquinoline derivatives (1â»4) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 µg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans.
Asunto(s)
Candida albicans/efectos de los fármacos , Hidroxiquinolinas/farmacología , Hifa/efectos de los fármacos , Streptomyces/química , Antifúngicos , Candida albicans/crecimiento & desarrollo , Regulación Fúngica de la Expresión Génica , Inhibidores de Crecimiento/farmacología , Hidroxiquinolinas/química , Hidroxiquinolinas/aislamiento & purificación , Hifa/crecimiento & desarrollo , Transducción de Señal , Streptomyces/metabolismoRESUMEN
The combination of investigating a unique source of chemically prolific bacterium with an LC/MS-based bacterial strain selection approach resulted in the discovery of two new secondary metabolites, buanmycin (1) and buanquinone (2), from the culture of a marine Streptomyces strain, which was isolated from a tidal mudflat in Buan, Republic of Korea. The carbon backbone of buanmycin (1), comprising 20 quaternary carbons out of 30 total carbons, was determined via (13)C-(13)C COSY NMR analysis after labeling 1 with (13)C by culturing the bacterium with (13)C-glucose. The complete structure of 1 was confidently elucidated, primarily based on 1D and 2D NMR spectroscopic and X-ray crystallographic analysis, as that of a new pentacyclic xanthone. The absolute configuration of the α-methyl serine unit in 1 was established by applying the advanced Marfey's method. The structure of buanquinone (2) was determined to be a new pentacyclic quinone based on NMR and MS spectroscopic data. Buanmycin exhibited potent cytotoxicity against colorectal carcinoma cells (HCT-116) and gastric carcinoma cells (SNU-638) with submicromolar IC50 values and strongly inhibited the pathogenic Gram-negative bacterium Salmonella enterica (MIC = 0.7 µM). In particular, buanmycin demonstrated inhibition of sortase A, which is a promising target for antibiotic discovery.
Asunto(s)
Actinobacteria/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Quinonas/aislamiento & purificación , Quinonas/farmacología , Streptomyces/química , Aminoaciltransferasas/efectos de los fármacos , Antibacterianos/química , Antineoplásicos/química , Proteínas Bacterianas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Cristalografía por Rayos X , Cisteína Endopeptidasas/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Bacterias Gramnegativas/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Quinonas/química , República de Corea , Staphylococcus aureus/efectos de los fármacosRESUMEN
Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2-nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and b-methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria.
Asunto(s)
Antibacterianos/farmacología , Organismos Acuáticos/microbiología , Depsipéptidos/farmacología , Streptomyces/metabolismo , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodosRESUMEN
Sortase A (SrtA), a type of transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall, is important in the virulence of gram-positive bacteria. Three compounds were isolated from marine-derived Streptomyces sp. MBTH32 using various chromatography techniques. The structures of these compounds were determined based on spectroscopic data and comparisons with previously reported data. Among the metabolites tested, lumichrome showed strong inhibitory activity against Staphylococcus aureus SrtA without affecting cell viability. The results of cell clumping activity assessment suggest the potential for using this compound to treat S. aureus infection by inhibiting SrtA activity.
Asunto(s)
Aminoaciltransferasas/antagonistas & inhibidores , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Fibrinógeno/metabolismo , Staphylococcus aureus/patogenicidad , Streptomyces/química , Aminoaciltransferasas/genética , Aminoaciltransferasas/metabolismo , Adhesión Bacteriana/efectos de los fármacos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Flavinas/química , Flavinas/aislamiento & purificación , Flavinas/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Mutación , Staphylococcus aureus/enzimología , Streptomyces/metabolismo , Virulencia/efectos de los fármacosRESUMEN
Bombyxamycins A and B (1 and 2) were discovered from a silkworm gut Streptomyces bacterium. Spectroscopic analysis and multiple-step chemical derivatization identified them as 26-membered cyclic lactams with polyene features. Bombyxamycin A showed significant antibacterial and antiproliferative effects. The bombyxamycin biosynthetic gene cluster was identified by genetic analysis. Gene deletion experiments confirmed that the cytochrome P450 BomK is responsible for the generation of 2, which unprecedentedly bears tetrahydrofuran in its macrocyclic ring.
Asunto(s)
Bombyx/química , Sistema Enzimático del Citocromo P-450/genética , Intestinos/fisiología , Lactamas Macrocíclicas/aislamiento & purificación , Animales , Sistema Enzimático del Citocromo P-450/química , Lactamas Macrocíclicas/química , Lactamas Macrocíclicas/metabolismo , Estructura Molecular , Familia de MultigenesRESUMEN
Candida albicans hyphal formation is inhibited by a quorum-sensing molecule, farnesoic acid, which accumulates in the medium as the cells proliferate. We recently showed that Pho81 is essential for the inhibition of hyphal growth by farnesoic acid. Here, we describe a newly identified regulator, Hot1, which increases the expression of PHO81. The binding site of Hot1 in the PHO81 promoter region was identified by DNase I protection assay. The hot1Δ mutant grows extensively as filaments. Furthermore, the inhibition of hyphal formation and the repression of major signaling pathway components in response to farnesoic acid are defective in hot1Δ mutant cells. These data suggest an important role for HOT1 in the inhibition of hyphal development by farnesoic acid in this fungus.
Asunto(s)
Candida albicans/metabolismo , Ácidos Grasos Insaturados/farmacología , Proteínas Fúngicas/genética , Hifa/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Sitios de Unión/genética , Candida albicans/genética , Candida albicans/crecimiento & desarrollo , Electroforesis en Gel de Poliacrilamida , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Hifa/crecimiento & desarrollo , Hifa/metabolismo , Morfogénesis/efectos de los fármacos , Morfogénesis/genética , Mutación , Regiones Promotoras Genéticas/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Factores de Transcripción/metabolismoRESUMEN
Sortases are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus (S. aureus), deletion of sortase isoform results in a significant reduction in virulence and infection potential. Twenty flavonoids were isolated from the stem of the folk medicinal plant Spatholobus suberectus Dunn. These compounds were tested against S. aureus-derived sortase A (SrtA), a key transpeptidase for bacterial virulence. Among these active flavonoids, 7-hydroxy-6-methoxy-flavanone (3) and formononetin (10) were identified as compounds with promising SrtA inhibitory activity. These compounds also exhibited inhibitory activity against S. aureus cell clumping to fibrinogen. The suppression of cell-clumping activity indicates the potential of these compounds in the treatment of S. aureus infections via the inhibition of SrtA.