Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-21
pubmed:abstractText
In recent years, there has been a dramatic increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2 (pulsed-field type USA400), the prototype CA-MRSA strain, is highly virulent and has enhanced ability to evade killing by neutrophils. Although progress has been made, the molecular basis for enhanced virulence of CA-MRSA remains incompletely defined. To that end, we studied resistance of MW2 to key microbicides of human neutrophils. Hydrogen peroxide (H2O2), hypochlorous acid, and azurophilic granule proteins had significant bacteriostatic but limited staphylocidal activity toward MW2 under the conditions tested. An MW2-specific microarray revealed common changes in S. aureus gene expression following exposure to each microbicide, such as up-regulation of transcripts involved in gene regulation (e.g., saeRS and kdpDE) and stress response. Azurophilic granule proteins elicited the greatest number of changes in MW2 transcripts, including up-regulation of mRNAs encoding multiple toxins and hemolysins (e.g., hlgA, hlgB, hlgC, hla, lukS-PV, lukF-PV, sec4, and set17-26). Notably, H2O2 triggered up-regulation of transcripts related to heme/iron uptake (e.g., isdA, isdB, and isdCDEFsrtBisdG), and an isogenic isdAB-negative strain of MW2 had increased susceptibility to H2O2 (p<0.001) and human neutrophils (p<0.05) compared with the wild-type parental strain. These findings reveal a S. aureus survival response wherein Iron-regulated surface determinant (Isd) proteins are important for resistance to innate host defense. Collectively, the data provide an enhanced view of the mechanisms used by S. aureus to circumvent destruction by the innate immune system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Infective Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Bacterial, http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins, http://linkedlifedata.com/resource/pubmed/chemical/Cation Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hemolysin Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Hypochlorous Acid, http://linkedlifedata.com/resource/pubmed/chemical/Iron, http://linkedlifedata.com/resource/pubmed/chemical/IsdA protein, Staphylococcus aureus, http://linkedlifedata.com/resource/pubmed/chemical/IsdB protein, Staphylococcus aureus
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
500-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18097052-Anti-Bacterial Agents, pubmed-meshheading:18097052-Anti-Infective Agents, pubmed-meshheading:18097052-Antigens, Bacterial, pubmed-meshheading:18097052-Bacterial Toxins, pubmed-meshheading:18097052-Cation Transport Proteins, pubmed-meshheading:18097052-Community-Acquired Infections, pubmed-meshheading:18097052-Gene Expression, pubmed-meshheading:18097052-Gene Expression Regulation, Bacterial, pubmed-meshheading:18097052-Hemolysin Proteins, pubmed-meshheading:18097052-Humans, pubmed-meshheading:18097052-Hydrogen Peroxide, pubmed-meshheading:18097052-Hypochlorous Acid, pubmed-meshheading:18097052-Immunity, Innate, pubmed-meshheading:18097052-Iron, pubmed-meshheading:18097052-Methicillin Resistance, pubmed-meshheading:18097052-Neutrophils, pubmed-meshheading:18097052-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:18097052-Staphylococcus aureus, pubmed-meshheading:18097052-Virulence
pubmed:year
2008
pubmed:articleTitle
Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus.
pubmed:affiliation
Laboratory of Human Bacterial Pathogenesis, Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural