Extracellular Proteome Analysis of<i>Leptospira interrogans</i>serovar Lai

Zeng, Lingbing; Zhang, Yunyi; Zhu, Yongzhang; Yin, Haidi; Zhuang, Xuran; Zhu, Wen‐Yuan; Guo, Xia; Qin, Jinhong

doi:10.1089/omi.2013.0043

Cited by 29 publications

(26 citation statements)

References 54 publications

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“…The methodology used in the present study identified 325 exoproteins (the L. interrogans genome encodes ϳ4,000 putative proteins), which is nearly 5-fold higher than the 66 proteins reported in a previous study (20). We propose two explanations for the observed difference in the number of proteins detected: first, protein precipitation, which was performed in the previous study and which can result in protein loss due to inefficient precipitation and resolubilization, was omitted in the present study.…”

Section: Discussioncontrasting

confidence: 60%

“…Proteins delivered to the extracellular space likely serve essential functions for the pathogenic and saprophytic lifestyles of Leptospira spp. Previous studies focusing on extracellular proteins identified Leptospira interrogans proteins in culture supernatants (20), while another study used a bioinformatics-based approach to identify potential outer membrane and extracellular proteins (21). It has also been demonstrated that culture supernatants of L. interrogans contain proteases which can interfere with the host complement defense against Leptospira spp.…”

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Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

et al. 2015

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bLeptospirosis is a life-threatening and emerging zoonotic disease with a worldwide annual occurrence of more than 1 million cases. Leptospirosis is caused by spirochetes belonging to the genus Leptospira. The mechanisms of disease manifestation in the host remain elusive, and the roles of leptospiral exoproteins in these processes have yet to be determined. Our aim in this study was to assess the composition and quantity of exoproteins of pathogenic Leptospira interrogans and to construe how these proteins contribute to disease pathogenesis. Label-free quantitative mass spectrometry of proteins obtained from Leptospira spirochetes cultured in vitro under conditions mimicking infection identified 325 exoproteins. The majority of these proteins are conserved in the nonpathogenic species Leptospira biflexa, and proteins involved in metabolism and energy-generating functions were overrepresented and displayed the highest relative abundance in culture supernatants. Conversely, proteins of unknown function, which represent the majority of pathogen-specific proteins (presumably involved in virulence mechanisms), were underrepresented. Characterization of various L. interrogans exoprotein mutants in the animal infection model revealed host mortality rates similar to those of hosts infected with wild-type L. interrogans. Collectively, these results indicate that pathogenic Leptospira exoproteins primarily function in heterotrophic processes (the processes by which organisms utilize organic substances as nutrient sources) to maintain the saprophytic lifestyle rather than the virulence of the bacteria. The underrepresentation of proteins homologous to known virulence factors, such as toxins and effectors in the exoproteome, also suggests that disease manifesting from Leptospira infection is likely caused by a combination of the primary and potentially moonlight functioning of exoproteins.

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confidence: 60%

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Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

et al. 2015

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“…Figure 1 depicts the distribution of T2S within the evolutionary tree of the Proteobacteria. Looking beyond the Proteobacteria, there are interesting examples of organisms that have a smaller number of T2S-related genes; e.g., Leptospira interrogans of the Spirochaetes encodes T2S CDEFGJKLMO, Chlamydia and Chlamydophila species within the Chlamydiae harbor genes for T2S CDEFG, Rhodopirellula baltica belonging to the Planctomycetes may encode T2S DEFGIKO, Aquifex aeolicus of the Aquificae carries homologs for T2S DEFGO, and Thermotoga maritima of the Thermotogae appears to encode T2S DEFG (10,(19)(20)(21)(22). In the case of Chlamydia trachomatis, one of these genes has been linked to protein secretion (20), suggesting that there may be different subclasses of T2S that deviate from the canonical system present in the Proteobacteria.…”

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Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

2017

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Type II secretion (T2S) is one means by which Gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. Based upon recent genome sequencing, it is clear that T2S is largely restricted to the Proteobacteria, occurring in many, but not all, genera in the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria classes. Prominent human and/or animal pathogens that express a T2S system(s) include Acinetobacter baumannii, Burkholderia pseudomallei, Chlamydia trachomatis, Escherichia coli, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Vibrio cholerae, and Yersinia enterocolitica. T2S-expressing plant pathogens include Dickeya dadantii, Erwinia amylovora, Pectobacterium carotovorum, Ralstonia solanacearum, Xanthomonas campestris, Xanthomonas oryzae, and Xylella fastidiosa. T2S also occurs in nonpathogenic bacteria, facilitating symbioses, among other things. The output of a T2S system can range from only one to dozens of secreted proteins, encompassing a diverse array of toxins, degradative enzymes, and other effectors, including novel proteins. Pathogenic processes mediated by T2S include the death of host cells, degradation of tissue, suppression of innate immunity, adherence to host surfaces, biofilm formation, invasion into and growth within host cells, nutrient assimilation, and alterations in host ion flux. The reach of T2S is perhaps best illustrated by those bacteria that clearly use it for both environmental survival and virulence; e.g., L. pneumophila employs T2S for infection of amoebae, growth within lung cells, dampening of cytokines, and tissue destruction. This minireview provides an update on the types of bacteria that have T2S, the kinds of proteins that are secreted via T2S, and how T2S substrates promote infection.KEYWORDS Legionella, T2S, type II secretion, Vibrio, animal pathogens, degradative enzymes, human pathogens, plant pathogens, toxins S ecreted proteins have a major role in the pathogenesis of bacterial infections, including important diseases of humans, animals, and plants. In the case of Gramnegative bacteria, there are seven secretion systems (types I, II, III, IV, V, VI, and IX) that mediate the export of "effector" proteins out of the bacterial cell and into the extracellular milieu or into target host cells (1-3). Type II secretion (T2S) was the first such system to be defined, based upon work done in the mid-1980s on pullulanase secretion by Klebsiella oxytoca (4). Further insight into T2S was then gained from the examination of Aeromonas, Pseudomonas, Vibrio, and a few additional members of the gammaproteobacteria (5, 6). Thus, T2S is considered a two-step process; i.e., proteins to be secreted are first carried across the inner membrane (IM) and into the periplasm by the Sec translocon (7) or Tat pathway (8) and then, after folding into a tertiary conformation (and in some instances, undergoing oligomerization), are transported across the outer membrane (...

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“…In these situations, the triggered SOS response is not only involved in DNA repair, but also influences antimicrobial resistance spread, general stress response and induction of virulence factors in organisms as uropathogenic E. coli, Salmonella enterica and Vibrio cholerae [10,49,50]. These mechanisms probably also occur in L. interrogans, and the full characterization of the DNA damage response is the first step to identify them.…”

Section: Discussionmentioning

confidence: 99%

“…Zeng et al [49] identified one of the ssb orthologous (LA1676) as component of the extracellular proteome, opening the possibility for a new function for SSB protein in leptospira physiology.…”

Section: Homologous Recombination (Hr)mentioning

confidence: 99%

Caracterization of the SOS response in Leptospira interrogans sorovar Copenhageni

Fonseca¹

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ACKNOWLEDGMENTS / AGRADECIMENTOSAgradeço aos vários mentores que tive ao longo desses 5 anos: ao Paulo Lee Ho, pela orientação e por me dar a liberdade necessária para desenvolver o projeto e deixá-lo com a minha cara; à Renata Costa, minha coorientadora de coração, pela amizade e empolgação científica compartilhada; ao Fredy Gueiros, por acompanhar meu doutorado e me ajudar mesmo sem ter nenhuma obrigação. Ao Alan Grossman, por abrir as portas do seu laboratório e me receber como uma das suas, sendo um verdadeiro mentor e exemplo de cientista.A todas as pessoas que fazem do Grossman's lab um lugar que dá vontade de voltar: Janet (pelos scripts e por não me deixar congelar no inverno), C. Lee (pela competência, paciência e vídeos de gatinho), Charlotte, Laurel e Monica (pela amizade e festas do brigadeiro).O Instituto Butantan é puro amor, e conheci muitas pessoas incríveis lá. Aos pesquisadores do Lab de Biotecnologia Molecular I (Jô, Enéas, Léo, Eliane, Alessandra), agradeço não só pelo apoio científico, mas pelos papos-cabeça, ensinamentos e por aguentarem meu mau-humor enquanto escrevia essa tese. Às técnicas Nídia e Aline, pois sem elas eu não encontraria nem minhas pipetas na bancada. A todas as amigas que fiz, Leptospira is a basal genus in an ancient group of bacteria, the spirochetes. The pathogenic species are responsible for leptospirosis, a disease with worldwide distribution and of public health importance in developed tropical countries. L. interrogans serovar Copenhageni is the agent for the majority of human leptospirosis in Brazil. In this work, we used a great variety of experimental approaches to characterize the SOS system in this serovar, to identify its impact in general DNA damage response, as well as to assess the DNA repair toolbox owned by pathogenic and saprophytic leptospires. We identified an additional repressor LexA, acquired by lateral gene transfer, exclusively in serovar Copenhageni. We also observed that UV-C irradiation led to massive death of cells and blockage of cell division in the survivors. Both repressors were active and we identified the sequences responsible for binding to promoters. However, the LexA1 SOS box was redefined after a de novo motif search on LexA1 ChIP-seq enriched sequences. This regulator was able to bind to at least 25 loci in the genome. DNA damage also caused a massive rearrangement of metabolism: increase in expression was observed in transposon and prophage genes, in addition to DNA repair pathways and mutagenesis inducers; on the other hand, motility, general metabolism and almost all virulence genes were repressed. Two induced prophages provided several proteins with useful functions. We also assessed the DNA repair-related genes presented by the three species of Leptospira: the saprophytic L.

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Extracellular Proteome Analysis ofLeptospira interrogansserovar Lai

Cited by 29 publications

References 54 publications

Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes

Expanding Role of Type II Secretion in Bacterial Pathogenesis and Beyond

Caracterization of the SOS response in Leptospira interrogans sorovar Copenhageni

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