Author
![]() |
MATSUNAGA, JAMES - UCLA, VETERANS AFFAIRS |
![]() |
LO, MIRANDA - MONASH UNIV., AUSTRALIA |
![]() |
BULACH, DIETER - MONASH UNIV., AUSTRALIA |
![]() |
Zuerner, Richard |
![]() |
ADLER, BEN - MONASH UNIV., AUSTRALIA |
![]() |
HAAKE, DAVID - UCLA, VETERANS AFFAIRS |
|
Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/11/2007 Publication Date: 6/1/2007 Citation: Matsunaga, J., Lo, M., Bulach, D.M., Zuerner, R.L., Adler, B., Haake, D.A. 2007. Response of Leptospira interrogans to Physiologic Osmolarity: Relevance in Signaling the Environment-to-Host Transition. Infection and Immunity. 1175(6):2864-2874. Interpretive Summary: Leptospirosis is a globally important zoonotic disease. Humans become infected via exposure to body fluids from infected animals, either directly or from contaminated water or soil. Invasion of the mammalian host involves an initial shift from conditions of a low salt to a high salt environment. Previous studies showed two proteins thought contribute to Leptospira infections are made when the salt concentration was increased. To gain a better understanding of how these bacteria respond to changes in their environment we used microarray technology to characterize global transcription profiles to identify factors, which could facilitate invasion and establishment of disease in the host in response to changes in salt concentration. Several genes were identified that may contribute to development of better vaccines to control the spread of leptospirosis. Technical Abstract: Transmission of pathogenic Leptospira between mammalian hosts usually involves dissemination via soil or water contaminated by the urine of reservoir hosts. The ability of Leptospira to adapt to the variety of conditions found inside and outside of the host is reflected in the relatively large genome size and high percentage of signal transduction genes. Invasion of host tissues by L. 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 adhesins LigA and LigB is strongly induced by an upshift in osmolarity to the level found in mammalian host tissues (~300 mOsm). These data suggest Leptospira may utilize changes in osmolarity to regulate important virulence characteristics. To better understand how L. interrogans serovar Copenhageni adapts to osmolar condiditons that correspond with invasion of a mammalian host, we quantified alterations in transcription using whole-genome microarrays. Overnight exposure in leptospiral culture medium supplemented with 120 mM sodium chloride significantly altered transcription of 6% of L. interrogans genes. Genes induced by physiologic osmolarity encoded a higher than expected number of proteins involved in signal transduction. Genes predicted to encode lipoproteins and those co-regulated by temperature were overrepresented among both salt-induced and salt-repressed genes. In contrast, leptospiral homologues of bacterial hyperosmolarity or general stress genes were not induced at physiologic osmolarity. These findings indicate that physiologic osmolarity may be an important signal for pathogenic leptospires to regulate gene expression during transition from ambient conditions to the host tissue environment. |
