Proteome scale comparative modeling for conserved drug and vaccine targets identification in Corynebacterium pseudotuberculosis
Syed Shah HassanSandeep TiwariLuís Carlos GuimarãesSyed Babar JamalEdson Luiz FoladorNeha Barve SharmaSiomar de Castro SoaresS. AlmeidaAmjad AliArshad IslamFabiana Dias PóvoaVinícius Augusto Carvalho de AbreuNeha JainAntaripa BhattacharyaLucky JunejaAnderson MiyoshiArtur SilvaDebmalya BarhAdrián G. TurjanskiVasco AzevedoRafaela Salgado Ferreira
60
Citation
95
Reference
10
Related Paper
Citation Trend
Abstract:
Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to a broad spectrum of hosts, including ruminants, thereby threatening economic and dairy industries worldwide. Currently there is no effective drug or vaccine available against Cp. To identify new targets, we adopted a novel integrative strategy, which began with the prediction of the modelome (tridimensional protein structures for the proteome of an organism, generated through comparative modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan-modelomics approach identified a set of 331 conserved proteins having 95-100% intra-species sequence similarity. Next, we combined subtractive proteomics and modelomics to reveal a set of 10 Cp proteins, which may be essential for the bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied all criteria of being putative targets. Additionally, we subjected these 4 proteins to virtual screening of a drug-like compound library. In all cases, molecules predicted to form favorable interactions and which showed high complementarity to the target were found among the top ranking compounds. The remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have homologs in the host proteomes. Their active site cavities were compared to the respective cavities in host proteins. We propose that some of these proteins can be selectively targeted using structure-based drug design approaches (SBDD). Our results facilitate the selection of C. pseudotuberculosis putative proteins for developing broad-spectrum novel drugs and vaccines. A few of the targets identified here have been validated in other microorganisms, suggesting that our modelome strategy is effective and can also be applicable to other pathogens.Keywords:
Corynebacterium pseudotuberculosis
Proteome
Caseous lymphadenitis
Corynebacterium
Caseous lymphadenitis, also called abscess disease, is an infectious, cosmopolitan disease. The causative agent is a Gram-positive bacillus, Corynebacterium pseudotuberculosis that is resistant to antibiotic treatment. Humans become infected with this bacillus, but the disease is considered a neglected zoonosis. The objective of this study was to estimate the prevalence and to identify Corynebacterium pseudotuberculosis in sheep slaughtered in central Algeria. For this purpose, 897 animals were examined and samples (pus) were taken from 12 sheep with abscesses to perform bacteriological study. Sex, age, and location of the abscess were noted. The results obtained showed an overall prevalence of 1.33%. The highest rate (50%) was observed in animals aged between 8 months and 1 year. Males were more affected by abscesses (66.7%) than females (33.3%). As for localisation, 41% of abscesses were found in the pulmonary lymph nodes and 25% in the submandibular region. Infection by Corynebacterium was estimated at a rate of 25%, lower than that obtained for Staphylococcus (41.7%). Regarding the zoonotic nature of the disease, the bacteria’s ability to survive in the external environment, and the high risk of contamination, management measures should be implemented for better disease control and prevention.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Zoonosis
Bacillus (shape)
Cite
Citations (0)
Caseous lymphadenitis is a chronic infectious disease caused by Corynebacterium pseudotuberculosis , which is a bacterium responsible for a great number of economic losses on goat and sheep production. It is characterized by the formation of abscesses in superficial lymph nodes and in internal organs and lymph nodes. This study aimed at determining the agreement between microbiological culture and PCR in the identification of C. pseudotuberculosis , in samples collected from animals in slaughterhouses and in animals that presented lymph node enlargement in field conditions. From the 202 samples analyzed through microbiological culture, 113 (56%) were positive for Corynebacterium sp.; from these positive samples, 38 (34%) were identified as C. pseudotuberculosis by microbiological culture. From the amount of samples, 110 (54%) were positive and 92 (46%) were negative in the PCR. Kappa index (0.193) presented a weak agreement between PCR and microbiological culture. We concluded that molecular diagnosis (PCR) in clinical samples proved to be more efficient, reproducible, and faster than the microbiological culture, both on clinical samples analyses and in the confirmation of C. pseudotuberculosis in colonies that were classified by Corynebacterium genus. Thus, the present study demonstrated the importance of PCR to confirm C. pseudotuberculosis diagnosis, and the best contribution for the epidemiological surveillance of the disease in sheep.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Microbiological culture
Cite
Citations (18)
Necropsy examinalions done in 658 goats have demonstrated that 17 (2.5%) presented hepatical abscess. Bacteriological examinations of purulent material enclosed in abscesses revealed the growth of Corynebacterium pseudotuberculosis ( 58,89%), Escherichia coli (1 1.75%), Corynebacterium sp (11.76%), Pasteurella haemolytica (5.88%), Proteus sp (5.88%) and Staphylococcus coagulase (+) (5.88%). Hepatical abscesses were more frequent in animals older than 13 months and were produced in their majority by Corynebacterium pseudotuberculosis, wich is the caseous lymphadenitis agent in goats. The hepatical abscesses were usually associated with other pathologies such as bronchopneumonia, caseous lymphadenis, gastrointestinal parasitism, umbilical infection, peritonitis, foot-rot, artritis, purulent meningomioencefalitis and starvation.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Caseous necrosis
Cite
Citations (1)
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Isolation
Homology
Cite
Citations (7)
Twenty-five strains of Corynebacterium pseudotuberculosis isolated from lesions of caseous lymphadenitis in goats were examined for their biochemical characteristics, antimicrobial susceptibility, and phospholipase D activity. The strains were uniform in biochemical reactions, cultural characteristics, and susceptibility to antimicrobial agents. Presence of urease and phospholipase D and absence of pyrazinamidase were valuable criteria in the identification of C. pseudotuberculosis.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Cite
Citations (53)
Corynebacterium pseudotuberculosis is a pathogen classified into two biovars: C. pseudotuberculosis biovar ovis, the etiologic agent of caseous lymphadenitis and C. pseudotuberculosis biovar equi, which causes ulcerative lymphangitis. The available whole genome sequences of different C. pseudotuberculosis strains have enabled identify difference of genes related both virulence and physiology of each biovar. To evaluate be this difference could reflect at proteomic level and to better understand the shared factors and the exclusive ones of biovar ovis and biovar equi strains, we applied the label-free quantitative proteomic to characterize the proteome of the strains: 1002_ovis and 258_equi, isolated from goat (Brazil) and equine (Belgium), respectively. From this analysis, we characterized a total of 1230 proteins in 1002_ovis and 1220 in 258_equi with high confidence. Moreover, the core-proteome between 1002_ovis and 258_equi obtained here is composed of 1122 proteins involved in different cellular processes, which could be necessary for the free living of C. pseudotuberculosis. In addition, 120 proteins from this core-proteome presented change in abundant with statistically significant differences. Considering the exclusive proteome, we detected strain-specific proteins to each strain. When correlated, the exclusive proteome of each strain and proteome with change in abundant, the proteomic differences, between the 1002_ovis and 258_equi, this related to proteins involved in cellular metabolism, information storage and processing, cellular processes and signaling. This study reports the first comparative proteomic study of the biovars ovis and equi of C. pseudotuberculosis. The results generated in this study provide information about factors which can contribute to understanding both the physiology and the virulence of this pathogen.
Biovar
Corynebacterium pseudotuberculosis
Proteome
Caseous lymphadenitis
Strain (injury)
Ovis
Cite
Citations (27)
Light and electron microscopic examinations were performed on kidneys of sheep infected with caseous lymphadenitis ( CLA ) caused by Corynebacterium pseudotuberculosis Membranproliferative glomerulonephritis was demonstrated. There were irregular thickenings of the glomeruelar basement membrane and glomerular cell proliferation, in contrast, no such lesions were found in the control lambs, indicating that CLA play a role in inducing glomerulorephritis
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Cite
Citations (0)
Caseous lymphadenitis is still a serious zoonotic problem in Turkey. Sheep suffer from the disease with yield loss in wool and meat production. Moreover, with inexperienced laboratory staff, biochemical identification may go unrevealed. The scope of this study was to demonstrate the presence of Corynebacterium pseudotuberculosis in sheep by PCR. The sampling was conducted via collecting lymph fluids from the lymph node internal pouch wall of 100 sheep that were examined for the presence of Corynebacterium pseudotuberculosis . Molecular identification of the Corynebacterium pseudotuberculosis isolates was carried out by establishing the presence of the proline iminopeptidase gene. All isolates were confirmed to be Corynebacterium pseudotuberculosis by polymerase chain reaction. The polymerase chain reaction procedure conducted in this research was observed to be reliable and fast, and could be utilized for confirmation of caseous lymphadenitis in sheep as an optional technique to time-consuming biochemical identification methods.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Corynebacterium diphtheriae
Cite
Citations (4)
Lambs were inoculated IV with 3.2 X 10(3) colony forming units (CFU) to 3.2 X 10(6) CFU of Corynebacterium pseudotuberculosis from a 6-hour broth culture supplemented with 0.1% sorbitan monooleate. After 28 days, multiple abscesses were observed in the lungs and lymph nodes. The number of abscesses in the lungs correlated with the inoculation dose. Two lambs given 10(5) CFU and 10(6) CFU died. Multiple abscesses occurred in other lambs given 10(6) CFU to 10(4) CFU and few abscesses occurred in lambs given 10(3) CFU. Corynebacterium pseudotuberculosis was isolated from lung abscesses, inoculation site abscesses, and lymph node abscesses, but not from normal tissues. Because this procedure consistently induced abscesses in the lungs, we believe it will be a suitable challenge system for studies on the prevention of caseous lymphadenitis in sheep.
Corynebacterium pseudotuberculosis
Caseous lymphadenitis
Corynebacterium
Colony-forming unit
Cite
Citations (16)
The relationship between the visceral form of caseous lymphadenitis and a chronic debilitating condition of mature sheep designated as the thin ewe syndrome was investigated. Internal abscesses were found during necropsy in 81% of animals with thin ewe syndrome and Corynebacterium pseudotuberculosis (C ovis) was recovered from 86% of the animals with internal abscesses. Other pyogenic bacteria, including C pyogenes, C equi, Staphylococcus epidermis, S aureus, and Pseudomonas aeruginosa were often recovered in association with C pseudotuberculosis. Moraxella sp was recovered in 41% of the animals with internal abscesses. In some abscesses, Moraxella sp was the dominant microorganism isolated and in others, they were outnumbered only by C pseudotuberculosis. Species isolated included M bovis, M osloensis, and M nonliquefaciens. The potential importance of Moraxella sp to the cause and pathogenesis of the thin ewe syndrome is not known. The results of the present study indicate that visceral caseous lymphadenitis is either an important contributing factor to the development of thin ewe syndrome or that the presence of thin ewe syndrome may predispose affected sheep to the development of visceral caseous lymphadenitis. A skin test reagent prepared by sonicating C pseudotuberculosis was of limited value in detecting animals with visceral caseous lymphadenitis. Only 56% of the animals with abscesses caused by C pseudotuberculosis gave positive delayed-type hypersensitivity skin test responses.
Caseous lymphadenitis
Corynebacterium pseudotuberculosis
Corynebacterium
Moraxella (Branhamella) catarrhalis
Cite
Citations (36)