INVESTIGADORES
RAIMUNDA Daniel Cesar
artículos
Título:
A Novel Zinc Binding System, ZevAB, Is Critical for Survival of Nontypeable Haemophilus influenzae in a Murine Lung Infection Model
Autor/es:
ROSADINI, CHARLES V.; GAWRONSKI, JEFFREY D; RAIMUNDA, DANIEL; ARGUEELLO, JOSE M; AKERLEY, BRIAN J.
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Año: 2011 vol. 79 p. 3366 - 3376
ISSN:
0019-9567
Resumen:
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.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.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.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.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.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.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.