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Infection and Immunity, June 2007, p. 2864-2874, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01619-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Response of Leptospira interrogans to Physiologic Osmolarity: Relevance in Signaling the Environment-to-Host Transition{triangledown} ,{dagger}

James Matsunaga,1,2* Miranda Lo,3 Dieter M. Bulach,3,4 Richard L. Zuerner,5 Ben Adler,3,4,6 and David A. Haake2,7

Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073,1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095,2 Australian Bacterial Pathogenesis Program, Monash University, Victoria 3800, Australia,3 Victorian Bioinformatics Consortium, Monash University, Victoria 3800, Australia,4 National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa 50010,5 Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Victoria 3800, Australia,6 Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 900737

Received 6 October 2006/ Returned for modification 19 November 2006/ Accepted 11 March 2007

Transmission of pathogenic Leptospira between mammalian hosts usually involves dissemination via soil or water contaminated by the urine of carrier animals. The ability of Leptospira to adapt to the diverse conditions found inside and outside the host is reflected in its relatively large genome size and high percentage of signal transduction genes. An exception is Leptospira borgpetersenii serovar Hardjo, which is transmitted by direct contact and appears to have lost genes necessary for survival outside the mammalian host. Invasion of host tissues by Leptospira interrogans involves a transition from a low osmolar environment outside the host to a higher physiologic osmolar environment within the host. Expression of the lipoprotein LigA and LigB adhesins is strongly induced by an upshift in osmolarity to the level found in mammalian host tissues. These data suggest that Leptospira utilizes changes in osmolarity to regulate virulence characteristics. To better understand how L. interrogans serovar Copenhageni adapts to osmolar conditions that correspond with invasion of a mammalian host, we quantified alterations in transcript levels using whole-genome microarrays. Overnight exposure in leptospiral culture medium supplemented with sodium chloride to physiologic osmolarity significantly altered the transcript levels of 6% of L. interrogans genes. Repressed genes were significantly more likely to be absent or pseudogenes in L. borgpetersenii, suggesting that osmolarity is relevant in studying the adaptation of L. interrogans to host conditions. Genes induced by physiologic osmolarity encoded a higher than expected number of proteins involved in signal transduction. Further, genes predicted to encode lipoproteins and those coregulated by temperature were overrepresented among both salt-induced and salt-repressed genes. In contrast, leptospiral homologues of hyperosmotic or general stress genes were not induced at physiologic osmolarity. These findings suggest that physiologic osmolarity is an important signal for regulation of gene expression by pathogenic leptospires during transition from ambient conditions to the host tissue environment.

* Corresponding author. Mailing address: Research Service, Mail code 151, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073. Phone: (310) 478-3711, ext. 42144. Fax: (310) 268-4063. E-mail: jamesm{at}ucla.edu

{triangledown} Published ahead of print on 19 March 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

Infection and Immunity, June 2007, p. 2864-2874, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01619-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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