Abstract
Bacteria activate a regulatory network in response to the challenges imposed by DNA damage to genetic material, known as the SOS response. This system is regulated by the RecA recombinase and by the transcriptional repressor lexA. Leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. This study aims to investigate the behavior of L. interrogans serovar Copenhageni after the stress induced by DNA damage. We show that L. interrogans serovar Copenhageni genome contains two genes encoding putative LexA proteins (lexA1 and lexA2) one of them being potentially acquired by lateral gene transfer. Both genes are induced after DNA damage, but the steady state levels of both LexA proteins drop, probably due to auto-proteolytic activity triggered in this condition. In addition, seven other genes were up-regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding hypothetical proteins. This set of genes is potentially regulated by LexA1, as it showed binding to their promoter regions. All these regions contain degenerated sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the other hand, LexA2 was able to bind to the palindrome TTGTAN 10TACAA, found in its own promoter region, but not in the others. Therefore, the L. interrogans serovar Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2 binding to divergent motifs. New possibilities for DNA damage response in Leptospira are expected, with potential influence in other biological responses such as virulence.
Highlights
Leptospira interrogans is one of the etiologic agents of leptospirosis, a worldwide disease with important economic and public health consequences, in particular to developing tropical countries [1,2]
L. interrogans serovar Copenhageni remains one of the serovars most refractory to genetic transformation and only two mutants were so far obtained by targeted mutagenesis [5,6]
In this study we show that the DNA damage induced by UVC irradiation triggered the SOS response in L. interrogans serovar Copenhageni
Summary
Leptospira interrogans is one of the etiologic agents of leptospirosis, a worldwide disease with important economic and public health consequences, in particular to developing tropical countries [1,2]. There are nine pathogenic species of Leptospira, divided in more than 260 serovars [4]. In Brazil, the majority of the leptospirosis cases in humans is the result of infection with serovar Copenhageni [1]. In spite of its social and economic impact, the molecular mechanisms of Leptospira pathogenesis are still poorly understood, as a consequence of the difficulties in their genetic manipulation. L. interrogans serovar Copenhageni remains one of the serovars most refractory to genetic transformation and only two mutants were so far obtained by targeted mutagenesis [5,6]
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