Arcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticum

Persistent Link:
http://hdl.handle.net/10150/610056
Title:
Arcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticum
Author:
Jost, B. H.; Lucas, Erynn; Billington, Stephen; Ratner, Adam; McGee, David
Affiliation:
Department of Veterinary Science and Microbiology, The University of Arizona, 1117 E Lowell Street, Tucson, AZ 85721, USA; Ventana Medical Systems, Inc., 1910 Innovation Park Drive, Oro Valley, AZ 85755, USA; Columbia University, Department of Pediatrics and Microbiology & Immunology, 650 W 168th Street BB443, New York, NY 10032, USA; Louisiana State University Health Sciences Center-Shreveport, Department of Microbiology & Immunology, 1501 Kings Highway, Shreveport, LA 71130, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Jost et al. BMC Microbiology 2011, 11:239 http://www.biomedcentral.com/1471-2180/11/239
Journal:
BMC Microbiology
Rights:
© 2011 Jost et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis, wound infections, and a variety of occasional invasive diseases. Since its initial discovery in 1946, this Gram positive organism has been known to have hemolytic activity, yet no hemolysin has been previously reported. A. haemolyticum also displays variable hemolytic activity on laboratory blood agar that is dependent upon which species the blood is derived.RESULTS:Here we describe a cholesterol-dependent cytolysin (CDC) secreted by A. haemolyticum, designated arcanolysin (aln), which is present in all strains (n = 52) tested by DNA dot hybridization. Among the known CDCs, ALN is most closely related to pyolysin (PLO) from Trueperella (formerly Arcanobacterium) pyogenes. The aln probe, however, did not hybridize to DNA from T. pyogenes. The aln open reading frame has a lower mol %G+C (46.7%) than the rest of the A. haemolyticum genome (53.1%) and is flanked by two tRNA genes, consistent with probable acquisition by horizontal transfer. The ALN protein (~ 64 kDa) contains a predicted signal sequence, a putative PEST sequence, and a variant undecapeptide within domain 4, which is typically important for function of the toxins. The gene encoding ALN was cloned and expressed in Escherichia coli as a functional recombinant toxin. Recombinant ALN had hemolytic activity on erythrocytes and cytolytic activity on cultured cells from human, rabbit, pig and horse origins but was poorly active on ovine, bovine, murine, and canine cells. ALN was less sensitive to inhibition by free cholesterol than perfringolysin O, consistent with the presence of the variant undecapeptide.CONCLUSIONS:ALN is a newly identified CDC with hemolytic activity and unique properties in the CDC family and may be a virulence determinant for A. haemolyticum.
EISSN:
1471-2180
DOI:
10.1186/1471-2180-11-239
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2180/11/239

Full metadata record

DC FieldValue Language
dc.contributor.authorJost, B. H.en
dc.contributor.authorLucas, Erynnen
dc.contributor.authorBillington, Stephenen
dc.contributor.authorRatner, Adamen
dc.contributor.authorMcGee, Daviden
dc.date.accessioned2016-05-20T08:57:33Z-
dc.date.available2016-05-20T08:57:33Z-
dc.date.issued2011en
dc.identifier.citationJost et al. BMC Microbiology 2011, 11:239 http://www.biomedcentral.com/1471-2180/11/239en
dc.identifier.doi10.1186/1471-2180-11-239en
dc.identifier.urihttp://hdl.handle.net/10150/610056-
dc.description.abstractBACKGROUND:Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis, wound infections, and a variety of occasional invasive diseases. Since its initial discovery in 1946, this Gram positive organism has been known to have hemolytic activity, yet no hemolysin has been previously reported. A. haemolyticum also displays variable hemolytic activity on laboratory blood agar that is dependent upon which species the blood is derived.RESULTS:Here we describe a cholesterol-dependent cytolysin (CDC) secreted by A. haemolyticum, designated arcanolysin (aln), which is present in all strains (n = 52) tested by DNA dot hybridization. Among the known CDCs, ALN is most closely related to pyolysin (PLO) from Trueperella (formerly Arcanobacterium) pyogenes. The aln probe, however, did not hybridize to DNA from T. pyogenes. The aln open reading frame has a lower mol %G+C (46.7%) than the rest of the A. haemolyticum genome (53.1%) and is flanked by two tRNA genes, consistent with probable acquisition by horizontal transfer. The ALN protein (~ 64 kDa) contains a predicted signal sequence, a putative PEST sequence, and a variant undecapeptide within domain 4, which is typically important for function of the toxins. The gene encoding ALN was cloned and expressed in Escherichia coli as a functional recombinant toxin. Recombinant ALN had hemolytic activity on erythrocytes and cytolytic activity on cultured cells from human, rabbit, pig and horse origins but was poorly active on ovine, bovine, murine, and canine cells. ALN was less sensitive to inhibition by free cholesterol than perfringolysin O, consistent with the presence of the variant undecapeptide.CONCLUSIONS:ALN is a newly identified CDC with hemolytic activity and unique properties in the CDC family and may be a virulence determinant for A. haemolyticum.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2180/11/239en
dc.rights© 2011 Jost et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleArcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticumen
dc.typeArticleen
dc.identifier.eissn1471-2180en
dc.contributor.departmentDepartment of Veterinary Science and Microbiology, The University of Arizona, 1117 E Lowell Street, Tucson, AZ 85721, USAen
dc.contributor.departmentVentana Medical Systems, Inc., 1910 Innovation Park Drive, Oro Valley, AZ 85755, USAen
dc.contributor.departmentColumbia University, Department of Pediatrics and Microbiology & Immunology, 650 W 168th Street BB443, New York, NY 10032, USAen
dc.contributor.departmentLouisiana State University Health Sciences Center-Shreveport, Department of Microbiology & Immunology, 1501 Kings Highway, Shreveport, LA 71130, USAen
dc.identifier.journalBMC Microbiologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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