J. Schmidt-brauns et al., Is a NAD pyrophosphatase activity necessary for Haemophilus influenzae type b multiplication in the blood stream?, INT J MED M, 291(3), 2001, pp. 219-225
Haemophilus influenzae has an absolute requirement for factor V because it
lacks all the biosynthetic enzymes necessary for the de novo synthesis of N
AD. Factor V can be provided as either nicotinamide adenosine dinucleotide
(NAD), nicotinamide mono-nucleotide (NMN) or nicotinamide riboside (NR) in
vitro, but little is known about the source or the mechanism of uptake for
factor V in vivo. Recently, a hypothetical open reading frame (ORF), termed
nadN, was identified to encode a gene product essential for H. influenzae
growth on NAD. Here, we report its role in the virulent H. influenzae serot
ype b strain Eagan. Our results indicate that NadN of type b Eagan strains
is involved in NAD uptake and in processing NAD to NR, which appears to be
the substrate for an as yet unidentified cytoplasmic membrane NR transport
system. Furthermore, we present data showing that H. influenzae type b nadN
mutants are able to survive as well as Eagan, in vivo in the five-day-old
infant rat model of human invasive disease. NAD pyrophosphatase and NMN 5'-
nucleotidase activities were present in rat and human serum, implying that
under infection conditions H. influenzae may obtain NR directly from its ho
st.