Journal article
Identification and Characterization of msf, a Novel Virulence Factor in Haemophilus influenzae
PloS one, v 11(3), pp e0149891-e0149891
2016
PMID: 26977929
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Haemophilus influenzae is an opportunistic pathogen. The emergence of virulent, non-typeable strains (NTHi) emphasizes the importance of developing new interventional targets. We screened the NTHi supragenome for genes encoding surface-exposed proteins suggestive of immune evasion, identifying a large family containing Sel1-like repeats (SLRs). Clustering identified ten SLR-containing gene subfamilies, each with various numbers of SLRs per gene. Individual strains also had varying numbers of SLR-containing genes from one or more of the subfamilies. Statistical genetic analyses of gene possession among 210 NTHi strains typed as either disease or carriage found a significant association between possession of the SlrVA subfamily (which we have termed, macrophage survival factor, msf) and the disease isolates. The PittII strain contains four chromosomally contiguous msf genes. Deleting all four of these genes (msfA1-4) (KO) resulted in a highly significant decrease in phagocytosis and survival in macrophages; which was fully complemented by a single copy of the msfA1 gene. Using the chinchilla model of otitis media and invasive disease, the KO strain displayed a significant decrease in fitness compared to the WT in co-infections; and in single infections, the KO lost its ability to invade the brain. The singly complemented strain showed only a partial ability to compete with the WT suggesting gene dosage is important in vivo. The transcriptional profiles of the KO and WT in planktonic growth were compared using the NTHi supragenome array, which revealed highly significant changes in the expression of operons involved in virulence and anaerobiosis. These findings demonstrate that the msfA1-4 genes are virulence factors for phagocytosis, persistence, and trafficking to non-mucosal sites.
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Details
- Title
- Identification and Characterization of msf, a Novel Virulence Factor in Haemophilus influenzae
- Creators
- Jennifer M Kress-Bennett - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of AmericaN Luisa Hiller - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of AmericaRory A Eutsey - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaEvan Powell - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaMark J Longwell - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaTodd Hillman - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaTenisha Blackwell - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaBarbara Byers - Center for Genomic Sciences, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of AmericaJoshua C Mell - Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of AmericaJ Christopher Post - Department of Otolaryngology, Head and Neck Surgery, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, Pennsylvania, United States of AmericaFen Z Hu - Department of Otolaryngology, Head and Neck Surgery, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, Pennsylvania, United States of AmericaGarth D Ehrlich - Department of Otolaryngology, Head and Neck Surgery, Drexel University College of Medicine, Allegheny Campus, Pittsburgh, Pennsylvania, United States of AmericaBenjamin A Janto - Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America
- Publication Details
- PloS one, v 11(3), pp e0149891-e0149891
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- R01 DC002148 / NIDCD NIH HHS R01 AI080935 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000372572800018
- Scopus ID
- 2-s2.0-84962223502
- Other Identifier
- 991014970033704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology