The interaction of macrophages and bacteria: Escherichia coli species, bacterial lipopolysaccharide, and lipid A differ in their ability to induce tumoricidal activity and the secretion of reactive nitrogen intermediates in macrophages

ABSTRACT During the course of a urinary tract infection, substantial levels of nitric oxide and reactive nitrogen intermediates are generated. We have found that many uropathogenic strains of Escherichia coli display far greater resistance to nitrosative stress than the K-12 reference strain MG1655. By selecting and screening for uropathogenic E. coli transposon mutants that are unable to grow in the presence of acidified nitrite, the cadC gene product was identified as a key facilitator of nitrosative stress resistance. Mutation of cadC, or its transcriptional targets cadA and cadB, results in loss of significant production of the polyamine cadaverine and increased sensitivity to acidified nitrite. Exogenous addition of cadaverine or other polyamines rescues growth of cad mutants under nitrosative stress. In wild-type cells, the concentration of cadaverine produced per cell is substantially increased by exposure to acidified nitrite. The mechanism behind polyamine-mediated rescue from nitrosative stress is unclear, but it is not attributable solely to chemical quenching of reactive nitrogen species or reduction in mutation frequency.

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Conditioning of Uropathogenic Escherichia coli for Enhanced Colonization of Host

Infection and Immunity ◽

10.1128/iai.01200-08 ◽

2009 ◽

Vol 77 (5) ◽

pp. 2104-2112 ◽

Cited By ~ 28

Author(s):

Jean M. Bower ◽

Hannah B. Gordon-Raagas ◽

Matthew A. Mulvey

Keyword(s):

Escherichia Coli ◽

Nitrosative Stress ◽

Model System ◽

Uropathogenic Escherichia Coli ◽

Reactive Nitrogen ◽

Reactive Nitrogen Intermediates ◽

Tract Infections ◽

K 12 ◽

In Transit ◽

Reference Strains

ABSTRACT While in transit within and between hosts, uropathogenic Escherichia coli (UPEC) encounters multiple stresses, including substantial levels of nitric oxide and reactive nitrogen intermediates. Here we show that UPEC, the primary cause of urinary tract infections, can be conditioned to grow at higher rates in the presence of acidified sodium nitrite (ASN), a model system used to generate nitrosative stress. When inoculated into the bladder of a mouse, ASN-conditioned UPEC bacteria are far more likely to establish an infection than nonconditioned bacteria. Microarray analysis of ASN-conditioned bacteria suggests that several NsrR-regulated genes and other stress- and polyamine-responsive factors may be partially responsible for this effect. Compared to K-12 reference strains, most UPEC isolates have increased resistance to ASN, and this resistance can be substantially enhanced by addition of the polyamine cadaverine. Nitrosative stress, as generated by ASN, can stimulate cadaverine synthesis by UPEC, and growth of UPEC in cadaverine-supplemented broth in the absence of ASN can also promote UPEC colonization of the bladder. These results suggest that UPEC interactions with polyamines or stresses such as reactive nitrogen intermediates can in effect reprogram the bacteria, enabling them to better colonize the host.

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Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: A comparative study in vitro and ex vivo

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(89)91764-6 ◽

1989 ◽

Vol 164 (3) ◽

pp. 968-973 ◽

Cited By ~ 31

Author(s):

R. Keller ◽

R. Keist

Keyword(s):

Comparative Study ◽

Ex Vivo ◽

Reactive Nitrogen ◽

Activated Macrophages ◽

Tumoricidal Activity ◽

Reactive Nitrogen Intermediates

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The NorR Protein of Escherichia coli Activates Expression of the Flavorubredoxin Gene norV in Response to Reactive Nitrogen Species

Journal of Bacteriology ◽

10.1128/jb.184.16.4640-4643.2002 ◽

2002 ◽

Vol 184 (16) ◽

pp. 4640-4643 ◽

Cited By ~ 90

Author(s):

Matthew I. Hutchings ◽

Neeraj Mandhana ◽

Stephen Spiro

Keyword(s):

Nitric Oxide ◽

Escherichia Coli ◽

Reactive Nitrogen Species ◽

Regulatory Gene ◽

Growth Conditions ◽

Anaerobic Growth ◽

Reactive Nitrogen ◽

Nitrogen Species ◽

Reactive Nitrogen Intermediates ◽

Nitric Oxide Detoxification

ABSTRACT The Escherichia coli norVW genes encode a flavorubredoxin and NADH:(flavo)rubredoxin reductase, respectively, which are involved in nitric oxide detoxification under anaerobic growth conditions. Here it is shown that the norVW genes also have a role in protection against reactive nitrogen intermediates generated from nitroprusside. Transcription from the norV promoter is activated by the presence of nitroprusside in the growth medium; activation requires the product of a divergently transcribed regulatory gene, norR.

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