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Antimicrobial Agents and Chemotherapy, October 2008, p. 3694-3700, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00172-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Benefit of Having Multiple ampD Genes for Acquiring β-Lactam Resistance without Losing Fitness and Virulence in Pseudomonas aeruginosa{triangledown}

Bartolomé Moya,1,2 Carlos Juan,1,2 Sebastián Albertí,2,3 José L. Pérez,1,2 and Antonio Oliver1,2*

Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta,1 Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS),2 Area de Microbiología, Universidad de las Islas Baleares, Palma de Mallorca, Spain3

Received 6 February 2008/ Returned for modification 23 April 2008/ Accepted 16 July 2008

The inactivation of ampD in Pseudomonas aeruginosa leads to a partially derepressed phenotype, characterized by a moderately high level basal ampC expression that is still further inducible, due to the presence of two additional ampD genes in this species (ampDh2 and ampDh3). The sequential inactivation of the three ampD genes was shown to lead to a stepwise upregulation of ampC expression, reaching full derepression in the triple mutant. To gain insight into the biological role of P. aeruginosa AmpD multiplicity, we determined the effects of the inactivation of the ampD genes on fitness and virulence. We show that, in contrast to what was previously documented for Salmonella spp., the inactivation of ampD in P. aeruginosa does not affect fitness or virulence in a mouse model of systemic infection. This lack of effect was demonstrated to be dependent on the presence of the additional ampD genes (ampDh2 and ampDh3), since the double and the triple ampD mutants completely lost their biological competitiveness and virulence; full ampC derepression and disruption of the AmpD peptidoglycan recycling system itself are both found to cause a major biological cost. Furthermore, among the ampD genes, ampDh3 is found to be the most relevant for virulence in P. aeruginosa. Therefore, as a consequence of the presence of additional ampD genes, partial ampC derepression mediated by ampD inactivation confers a biologically efficient resistance mechanism on P. aeruginosa.

* Corresponding author. Mailing address: Servicio de Microbiología, Hospital Son Dureta, C. Andrea Doria No. 55, 07014 Palma de Mallorca, Spain. Phone and fax: 34 971 175 185. E-mail: aoliver{at}hsd.es

{triangledown} Published ahead of print on 21 July 2008.

Antimicrobial Agents and Chemotherapy, October 2008, p. 3694-3700, Vol. 52, No. 10
0066-4804/08/$08.00+0     doi:10.1128/AAC.00172-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lister, P. D., Wolter, D. J., Hanson, N. D. (2009). Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms. Clin. Microbiol. Rev. 22: 582-610 [Abstract] [Full Text]  
  • Asgarali, A., Stubbs, K. A., Oliver, A., Vocadlo, D. J., Mark, B. L. (2009). Inactivation of the Glycoside Hydrolase NagZ Attenuates Antipseudomonal {beta}-Lactam Resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 2274-2282 [Abstract] [Full Text]  
  • Jacoby, G. A. (2009). AmpC {beta}-Lactamases. Clin. Microbiol. Rev. 22: 161-182 [Abstract] [Full Text]  


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