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Journal of Bacteriology, April 2004, p. 2164-2172, Vol. 186, No. 7
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.7.2164-2172.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Comparative Genomics of Two Leptospira interrogans Serovars Reveals Novel Insights into Physiology and Pathogenesis

A. L. T. O. Nascimento,^1* A. I. Ko,^2,3 E. A. L. Martins,¹ C. B. Monteiro-Vitorello,⁴ P. L. Ho,¹ D. A. Haake,^5,6 S. Verjovski-Almeida,⁷ R. A. Hartskeerl,⁸ M. V. Marques,⁹ M. C. Oliveira,¹⁰ C. F. M. Menck,⁹ L. C. C. Leite,¹ H. Carrer,⁴ L. L. Coutinho,⁴ W. M. Degrave,¹¹ O. A. Dellagostin,¹² H. El-Dorry,⁷ E. S. Ferro,⁹ M. I. T. Ferro,¹³ L. R. Furlan,^13, M. Gamberini,¹ E. A. Giglioti,¹⁴ A. Góes-Neto,¹⁵ G. H. Goldman,¹⁶ M. H. S. Goldman,¹⁷ R. Harakava,¹⁸ S. M. B Jerônimo,¹⁹ I. L. M. Junqueira-de-Azevedo,¹ E. T. Kimura,⁹ E. E. Kuramae,²⁰ E. G. M. Lemos,¹³ M. V. F. Lemos,¹³ C. L. Marino,²¹ L. R. Nunes,²² R. C. de Oliveira,²² G. G. Pereira,²³ M. S. Reis,²⁴ A. Schriefer,²⁵ W. J. Siqueira,²⁵ P. Sommer,¹⁹ S. M. Tsai,²⁷ A. J. G. Simpson,²⁸ J. A. Ferro,¹³ L. E. A. Camargo,⁴ J. P. Kitajima,^29, J. C. Setubal,²⁴ and M. A. Van Sluys¹⁰

Centro de Biotecnologia, Instituto Butantan,¹ Instituto de Química,⁷ Instituto de Ciências Biomédicas,⁹ Instituto de Biociências,¹⁰ Instituto Biológico, Universidade de São Paulo, São Paulo,¹⁸ Escola Superior de Agricultura Luiz de Queiroz,⁴ Centro de Energia Nuclear na Agricultura, Universidade de São Paulo, Piracicaba,²⁷ Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista, Jaboticabal,¹³ Centro de Ciências Agrárias, Universidade Federal de São Carlos, Araras,¹⁴ Faculdade de Ciencias Farmaceuticas de Ribeirão Preto,¹⁶ Faculdade de Filosofia, Ciências e Letras, Universidade de São Paulo, Ribeirão Preto,¹⁷ Faculdade de Ciências Agronômicas,²⁰ Instituto de Biociências, Universidade Estadual Paulista, Botucatu,²¹ Núcleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes, Mogi das Cruzes,²² Departamento de Genética e Evolução,²³ Instituto de Computação,²⁴ Instituto Agronômico de Campinas,²⁶ Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, São Paulo,²⁹ Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz/Ministério da Saúde,² Hospital Universitário Professor Edgard Santos, Serviço de Imunologia, Universidade Federal da Bahia, Salvador,²⁵ Laboratório de Pesquisa em Microbiologia (LAPEM), Departamento de Ciências Biológicas, Universidade Estadual de Feira de Santana (UEFS), Feira de Santana, Bahia,¹⁵ Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro,¹¹ Centro de Biotecnologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul,¹² Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil,¹⁹ Division of International Medicine and Infectious Disease, Weill Medical College of Cornell University,³ Ludwig Institute for Cancer Research, New York, New York,²⁸ University of California—Los Angeles School of Medicine,⁵ Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California,⁶ KIT (Koninklijk Instituut voor de Tropen/Royal Tropical Institute), KIT Biomedical Research, Amsterdam, The Netherlands⁸

Received 23 September 2003/ Accepted 3 December 2003

Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.

Supplemental material for this article may be found at http://jb.asm.org.

Present address: Alellyx Applied Genomics, Rua James Clerk Maxwell 320, Techno Park, 13067-850, Campinas, SP, Brazil.

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