Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling

Junguk Park; Reshma Jagasia; Gunnar F. Kaufmann; John C. Mathison; Diana I. Ruiz; Jason A. Moss; Michael M. Meijler; Richard J. Ulevitch; Kim D. Janda

doi:10.1016/j.chembiol.2007.08.013

Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling

Junguk Park, Reshma Jagasia, Gunnar F. Kaufmann, John C. Mathison, Diana I. Ruiz, Jason A. Moss, Michael M. Meijler, Richard J. Ulevitch, Kim D. Janda

Research output: Contribution to journal › Article › peer-review

208 Scopus citations

Abstract

Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

Original language	English
Pages (from-to)	1119-1127
Number of pages	9
Journal	Chemistry and Biology
Volume	14
Issue number	10
DOIs	https://doi.org/10.1016/j.chembiol.2007.08.013
State	Published - 26 Oct 2007
Externally published	Yes

Keywords

CHEMBIO
MICROBIO

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

Access to Document

10.1016/j.chembiol.2007.08.013

Cite this

@article{3604dca9a37b44f1b7827f0af1975ffe,

title = "Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling",

abstract = "Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.",

keywords = "CHEMBIO, MICROBIO",

author = "Junguk Park and Reshma Jagasia and Kaufmann, {Gunnar F.} and Mathison, {John C.} and Ruiz, {Diana I.} and Moss, {Jason A.} and Meijler, {Michael M.} and Ulevitch, {Richard J.} and Janda, {Kim D.}",

note = "Funding Information: We are grateful to Dr. Richard P. Novick (Skirball Institute, New York University Medical Center) for the generous gift of RN4850. We also thank the TSRI Antibody Production Core Facility for providing the purified monoclonal antibodies. A clinical isolate, NRS168, was obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) program supported by the NIAID/NIH (N01-AI-95359). This work was supported by the National Institutes of Health (AI055778 to K.D.J.) and The Skaggs Institute for Chemical Biology. The authors declare no competing financial interests. ",

year = "2007",

month = oct,

day = "26",

doi = "10.1016/j.chembiol.2007.08.013",

language = "English",

volume = "14",

pages = "1119--1127",

journal = "Chemistry and Biology",

issn = "1074-5521",

publisher = "Elsevier Inc.",

number = "10",

}

TY - JOUR

T1 - Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling

AU - Park, Junguk

AU - Jagasia, Reshma

AU - Kaufmann, Gunnar F.

AU - Mathison, John C.

AU - Ruiz, Diana I.

AU - Moss, Jason A.

AU - Meijler, Michael M.

AU - Ulevitch, Richard J.

AU - Janda, Kim D.

N1 - Funding Information: We are grateful to Dr. Richard P. Novick (Skirball Institute, New York University Medical Center) for the generous gift of RN4850. We also thank the TSRI Antibody Production Core Facility for providing the purified monoclonal antibodies. A clinical isolate, NRS168, was obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) program supported by the NIAID/NIH (N01-AI-95359). This work was supported by the National Institutes of Health (AI055778 to K.D.J.) and The Skaggs Institute for Chemical Biology. The authors declare no competing financial interests.

PY - 2007/10/26

Y1 - 2007/10/26

N2 - Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

AB - Quorum sensing (QS) is the process through which bacteria communicate utilizing small diffusible molecules termed autoinducers. It has been demonstrated that QS controls a plethora of microbial processes including the expression of virulence factors. Here we report an immunopharmacotherapeutic approach for the attenuation of QS in the Gram-positive human pathogen Staphylococcus aureus. An anti-autoinducer monoclonal antibody, AP4-24H11, was elicited against a rationally designed hapten, and efficiently inhibited QS in vitro through the sequestration of the autoinducing peptide (AIP)-4 produced by S. aureus RN4850. Importantly, AP4-24H11 suppressed S. aureus pathogenicity in an abscess formation mouse model in vivo and provided complete protection against a lethal S. aureus challenge. These findings provide a strong foundation for further investigations of immunopharmacotherapy for the treatment of bacterial infections in which QS controls the expression of virulence factors.

KW - CHEMBIO

KW - MICROBIO

UR - http://www.scopus.com/inward/record.url?scp=35348974568&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2007.08.013

DO - 10.1016/j.chembiol.2007.08.013

M3 - Article

C2 - 17961824

AN - SCOPUS:35348974568

SN - 1074-5521

VL - 14

SP - 1119

EP - 1127

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 10

ER -

Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this