What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Painter, Kimberley L.; Krishna, Aishwarya; Wigneshweraraj, Sivaramesh; Edwards, Andrew M.

doi:10.1016/j.tim.2014.09.002

Cited by 147 publications

(143 citation statements)

References 99 publications

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“…With these ideas in mind, our research raises the exciting, but now plausible possibility that surfaces decorated with quorum-sensing-modulating molecules can be assessed for anti-infective properties in animal models harboring indwelling devices. We note that instances of Agr-deficient virulent S. aureus strains have been reported 44 . Infections by Agr-defective strains primarily occur in patients that have been subjected to extreme courses of antibiotics and/or that have impaired immune functions 44 .…”

Section: Discussionmentioning

confidence: 79%

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Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

et al. 2017

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Bacteria use a process called quorum sensing to communicate and orchestrate collective behaviors including virulence factor secretion and biofilm formation. Quorum sensing relies on production, release, accumulation, and population-wide detection of signal molecules called autoinducers. Here, we develop concepts to coat surfaces with quorum-sensing-manipulation molecules as a method to control collective behaviors. We probe this strategy using Staphylococcus aureus. Pro- and anti-quorum-sensing molecules can be covalently attached to surfaces using click chemistry, where they retain their abilities to influence bacterial behaviors. We investigate key features of the compounds, linkers, and surfaces necessary to appropriately position molecules to interact with cognate receptors, and the ability of modified surfaces to resist long-term storage, repeated infections, host plasma components, and flow-generated stresses. Our studies highlight how this surface approach can be used to make colonization-resistant materials against S. aureus and other pathogens and how the approach can be adapted to promote beneficial behaviors of bacteria on surfaces.

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Section: Discussionmentioning

confidence: 79%

“…We note that instances of Agr-deficient virulent S. aureus strains have been reported 44 . Infections by Agr-defective strains primarily occur in patients that have been subjected to extreme courses of antibiotics and/or that have impaired immune functions 44 . Such strains would not be vulnerable to the strategies proposed here.…”

Section: Discussionmentioning

confidence: 79%

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

et al. 2017

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“…Both similarities and differences exist between the Agr-like QS system of C. perfringens and the well-characterized, paradigm Agr system of Staphylococcus aureus (8,12,13,(19)(20)(21). For example, the C. perfringens Agr-like QS system includes an operon encoding AgrD and AgrB, where AgrD is the precursor peptide for the autoinducing peptide (AIP) that mediates Agr QS signaling and AgrB is the integral membrane endopeptidase that is involved in processing AgrD to the active AIP.…”

mentioning

confidence: 99%

“…For example, the C. perfringens Agr-like QS system includes an operon encoding AgrD and AgrB, where AgrD is the precursor peptide for the autoinducing peptide (AIP) that mediates Agr QS signaling and AgrB is the integral membrane endopeptidase that is involved in processing AgrD to the active AIP. However, C. perfringens lacks the AgrA/AgrC two-component system that responds to the AIP in S. aureus (6,8,19,20). Some evidence suggests that the VirS/VirR two-component regulatory system may sometimes be the functional equivalent of AgrA/AgrC in C. perfringens, but this relationship has not yet been firmly proven and there appears to be exceptions since expression of the C. perfringens etx gene is regulated by the Agr-like QS system, yet etx expression is not affected by inactivation of the virS-virR operon (6,8,12,14).…”

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confidence: 99%

Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System

McClane

2015

J Bacteriol

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.07925.x) that an 8-amino-acid, AgrD-derived peptide named 8-R upregulates CPB production by this QS system. The current study synthesized a series of small signaling peptides corresponding to sequences within the C. perfringens AgrD polypeptide to investigate the C. perfringens autoinducing peptide (AIP) structure-function relationship. When both linear and cyclic ring forms of these peptides were added to agrB null mutants of type B strain CN1795 or type C strain CN3685, the 5-amino-acid peptides, whether in a linear or ring (thiolactone or lactone) form, induced better signaling (more CPB production) than peptide 8-R for both C. perfringens strains. The 5-mer thiolactone ring peptide induced faster signaling than the 5-mer linear peptide. Strain-related variations in sensing these peptides were detected, with CN3685 sensing the synthetic peptides more strongly than CN1795. Consistent with those synthetic peptide results, Transwell coculture experiments showed that CN3685 exquisitely senses native AIP signals from other isolates (types A, B, C, and D), while CN1795 barely senses even its own AIP. Finally, a C. perfringens AgrD sequence-based peptide with a 6-amino-acid thiolactone ring interfered with CPB production by several C. perfringens strains, suggesting potential therapeutic applications. These results indicate that AIP signaling sensitivity and responsiveness vary among C. perfringens strains and suggest C. perfringens prefers a 5-mer AIP to initiate Agr signaling. IMPORTANCEClostridium perfringens possesses an Agr-like quorum sensing (QS) system that regulates virulence, sporulation, and toxin production. The current study used synthetic peptides to identify the structure-function relationship for the signaling peptide that activates this QS system. We found that a 5-mer peptide induces optimal signaling. Unlike other Agr systems, a linear version of this peptide (in addition to thiolactone and lactone versions) could induce signaling. Two C. perfringens strains were found to vary in sensitivity to these peptides. We also found that a 6-mer peptide can inhibit toxin production by some strains, suggesting therapeutic applications. In humans and livestock, Clostridium perfringens is a major cause of histotoxic infections, such as human gas gangrene, and intestinal infections, including enteritis and enterotoxemias (1, 2). The versatility of this Gram-positive anaerobic bacterium is largely attributable to its ability to produce ϳ17 different toxins (3-5). However, individual strains produce only portions of this toxin repertoire; this toxin production variability is used in a classification system that assigns C. perfringens isolates to one of five types (A to E) based upon their production of alpha (CPA), beta (CPB), epsilon (ETX), and iota toxins (4, 5). Each C. perfringens type is associated with certain diseases (1, 4).C. perfringens-induced diseases are not intoxications but rather true infections where the bacterium must grow and produce toxins in the host (1). There is only a relatively rudiment...

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“…Esta autofosforilación se forma por un cambio inducido por el AIP en la conformación de AgrC, que permite una conexión entre el sensor y la quinasa (Painter, et al, 2014 Por lo tanto, si se interrumpe la expresión de genes que se asocien al operon agr, la producción de factores de virulencia también se verá interrumpida. Bajo esta condición, la bacteria pierde su capacidad de colonizar y causar daño.…”

Section: Introductionunclassified

Inhibición de la expresión del sistema agr de Staphylococcus aureus resistente a meticilina mediante el uso de polifenoles totales de hojas de aguacate mexicano (Persea americana var. drymifolia)

Moreno¹,

Ramos

Martínez-Ávila

et al. 2017

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Resumen IntroducciónLa resistencia a los antibióticos por parte de las bacterias está provocando gran impacto negativo en la salud humana y en la producción animal. Actualmente, Staphylococcus aureus es considerada dentro de los seis principales grupos bacterianos con mayores reportes de aparición de resistencia a nivel mundial. Por otro lado, durante décadas las plantas de uso medicinal han sido fuente importante de compuestos bactericidas; sin embargo, también se ha empezado a documentar otras moléculas con otros mecanismos antimicrobianos, como es la inhibición de la percepción de quórum (anti-percepción de quórum (APQ)). En la medicina tradicional mexicana las hojas de aguacate mexicano (Persea americana var drymifolia) han sido empleadas para tratar diversos padecimientos que involucran infecciones bacterianas, por lo que es factible contenga compuestos que posean efectos antioxidantes, bactericidas y APQ, que ayuden a combatir las infecciones de cepas resistentes. De tal manera, que el objetivo de esta investigación fue determinar el efecto de los polifenoles totales de las hojas de Persea americana var.drymifolia y su actividad APQ sobre cepas de S. aureus resistentes a meticilina (MRSA). MétodosSe obtuvieron los polifenoles presentes en las hojas de 18 cultivares de aguacate mexicano mediante extracción asistida por ultrasonido y fueron purificados en una columna de amberlita. Discusión y ConclusiónLos polifenoles extraídos de las hojas de aguacate mexicano, exhiben principalmente actividad bactericida, pero también inhiben la expresión de genes asociados a la percepción de quórum de cepas de S. aureus MRSA. De igual manera, presentan una buena actividad antioxidante, lo que en conjunto puede ayudar a contrarrestar las infecciones con cepas resistentes de manera más eficiente. Por lo tanto, las hojas de aguacate mexicano son una fuente importante de metabolitos antioxidantes, bactericidas y APQ. Abstract IntroductionBacteria resistant to antibiotics are important due to great negative impact on both, human health and animal production. Currently, Staphylococcus aureus is considered one of the six main bacterial groups with the highest reports of emergence resistance around the world. On the other hand, for decades the use of medicinal plants, have been important source of bactericidal compounds; however, there are other kind of molecules with many antimicrobial mechanisms such as phenolic compounds; which as antiquorum sensing (AQS) effect. In the mexican traditional medicine the creole avocado leaves (Persea americana var drymifolia), have been used to treat various diseases involving bacterial infections. In this sense, it is possible to find compounds with antioxidant, bactericidal and AQS effects, which could help to eradicate

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What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Cited by 147 publications

References 99 publications

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development

Structure-Function Analysis of Peptide Signaling in the Clostridium perfringens Agr-Like Quorum Sensing System

Inhibición de la expresión del sistema agr de Staphylococcus aureus resistente a meticilina mediante el uso de polifenoles totales de hojas de aguacate mexicano (Persea americana var. drymifolia)

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