The capability of Pseudomonas aeruginosa to recruit zinc under conditions of limited metal availability is affected by inactivation of the ZnuABC transporter.
The ability of a large number of bacterial pathogens to multiply in the infected host and cause disease is dependent on their ability to express high affinity zinc importers. In many bacteria, ZnuABC, a transporter of the ABC family, plays a central role in the process of zinc uptake in zinc poor environments, including the tissues of the infected host. To initiate an investigation into the relevance of the zinc uptake apparatus for Pseudomonas aeruginosa pathogenicity, we have generated a znuA mutant in the PA14 strain. We have found that this mutant strain displays a limited growth defect in zinc depleted media. The znuA mutant strain is more sensitive than the wild type strain to calprotectin-mediated growth inhibition, but both the strains are highly resistant to this zinc sequestering antimicrobial protein. Moreover, intracellular zinc content is not evidently affected by inactivation of the ZnuABC transporter. These findings suggest that P. aeruginosa is equipped with redundant mechanisms for the acquisition of zinc that might favor P. aeruginosa colonization of environments containing low levels of this metal. Nonetheless, deletion of znuA affects alginate production, reduces the activity of extracellular zinc-containing proteases, including LasA, LasB and protease IV, and decreases the ability of P. aeruginosa to disseminate during systemic infections. These results indicate that efficient zinc acquisition is critical for the expression of various virulence features typical of P. aeruginosa and that ZnuABC also plays an important role in zinc homeostasis in this microorganism.
Department of Biology, University of Rome Tor Vergata, 00133 Roma, Italy. andrea.battistoni@uniroma2.it.
Melania
M
D'Orazio
Maria Chiara
MC
Mastropasqua
Mauro
M
Cerasi
Francesca
F
Pacello
Ada
A
Consalvo
Barbara
B
Chirullo
Brittany
B
Mortensen
Eric P
EP
Skaar
Domenico
D
Ciavardelli
Paolo
P
Pasquali
Andrea
A
Battistoni
D000464:Alginates; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D005260:Female; D005798:Genes, Bacterial; D020723:Glucuronic Acid / Q000096:biosynthesis; D006603:Hexuronic Acids; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*
D000464:Alginates; D001426:Bacterial Proteins; D006603:Hexuronic Acids; D026901:Membrane Transport Proteins; D020723:Glucuronic Acid; D010447:Peptide Hydrolases; D015032:Zinc