GSBS Student Publications

Student Author(s)

Charles V. Rosadini

GSBS Program

Molecular Genetics & Microbiology

UMMS Affiliation

Department of Microbiology and Physiological Systems

Date

8-1-2011

Document Type

Article

Medical Subject Headings

Animals; Culture Media; Female; Gene Knockout Techniques; Haemophilus Infections; Haemophilus influenzae; Lung; Mice; Mice, Inbred C57BL; Microbial Viability; Mutagenesis, Insertional; Pneumonia, Bacterial; Protein Binding; Virulence; Virulence Factors; Zinc

Disciplines

Life Sciences | Medicine and Health Sciences | Microbiology | Physiology

Abstract

Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of zevA (HI1249) and zevB (HI1248). NTHI mutants of zevA and zevB grew normally in rich medium but were defective for colonization in a mouse lung model. Mutants also exhibited severe growth defects in medium containing EDTA and were rescued by supplementation with zinc. Additionally, purified recombinant ZevA was found to bind to zinc with high affinity. Together, these data demonstrate that zevAB is a novel virulence factor important for zinc utilization of H. influenzae under conditions where zinc is limiting. Furthermore, evidence presented here suggests that zinc limitation is likely an important mechanism for host defense against pathogens during lung infection.

Rights and Permissions

Citation: Infect Immun. 2011 Aug;79(8):3366-76. Epub 2011 May 16. Link to article on publisher's website

Related Resources

Link to article in PubMed

PubMed ID

21576338

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.