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Vladimir Frecer - One of the best experts on this subject based on the ideXlab platform.
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qsar analysis of antimicrobial and Haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin 1
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Vladimir FrecerAbstract:Abstract In this paper we quantitatively analyse antimicrobial and Haemolytic activities of porcine protegrin-1 (PG-1) mimetics—cyclic cationic peptides with β-hairpin fold synthesised by Robinson et al. [Bioorg. Med. Chem. 2005, 13, 2055]. The presented QSAR models, which use molecular properties related to possible mechanisms of cell membrane disruption that can be easily calculated from available data on amino acids, rationalize the relationships between sequences and antimicrobial and Haemolytic potencies of the cyclic peptides. The best models obtained by application of genetic function approximation algorithm correlate antimicrobial potencies to the peptide’s charge and amphipathicity index, while the Haemolytic effect correlates well with the lipophilicity of residues forming the nonpolar face of the β-hairpin. The models permit selection of site-directed residue substitutions leading to simultaneous optimization of antimicrobial and Haemolytic potencies. Examples of such residue substitutions in the nonpolar face of a symmetric cyclic β-hairpin PG-1 analogue with an ideal amphipathic structure are given.
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qsar analysis of antimicrobial and Haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin 1
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Vladimir FrecerAbstract:Abstract In this paper we quantitatively analyse antimicrobial and Haemolytic activities of porcine protegrin-1 (PG-1) mimetics—cyclic cationic peptides with β-hairpin fold synthesised by Robinson et al. [Bioorg. Med. Chem. 2005, 13, 2055]. The presented QSAR models, which use molecular properties related to possible mechanisms of cell membrane disruption that can be easily calculated from available data on amino acids, rationalize the relationships between sequences and antimicrobial and Haemolytic potencies of the cyclic peptides. The best models obtained by application of genetic function approximation algorithm correlate antimicrobial potencies to the peptide’s charge and amphipathicity index, while the Haemolytic effect correlates well with the lipophilicity of residues forming the nonpolar face of the β-hairpin. The models permit selection of site-directed residue substitutions leading to simultaneous optimization of antimicrobial and Haemolytic potencies. Examples of such residue substitutions in the nonpolar face of a symmetric cyclic β-hairpin PG-1 analogue with an ideal amphipathic structure are given.
Maxime Mahu - One of the best experts on this subject based on the ideXlab platform.
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Weakly Haemolytic variants of Brachyspira hyodysenteriae newly emerged in Europe belong to a distinct subclade with unique genetic properties
Veterinary Research, 2019Co-Authors: Roderick M. Card, Maxime Mahu, Nyree D. Phillips, David J. Hampson, Eric R. Burrough, Richard J. Ellis, Javier Nunez-garcia, Jill R. Thomson, Judith Rohde, Alexander W. TuckerAbstract:Brachyspira ( B. ) hyodysenteriae is widespread globally, and can cause mucohaemorrhagic colitis (swine dysentery, SD) with severe economic impact in infected herds. Typical strains of B. hyodysenteriae are strongly Haemolytic on blood agar, and the Haemolytic activity is believed to contribute to virulence in vivo. However, recently there have been reports of atypical weakly Haemolytic isolates of B. hyodysenteriae (whBh). In this study, 34 European whBh and 82 strongly Haemolytic isolates were subjected to comparative genomic analysis. A phylogenetic tree constructed using core single nucleotide polymorphisms showed that the whBh formed a distinct sub-clade. All eight genes previously associated with haemolysis in B. hyodysenteriae were present in the whBh. No consistent patterns of amino acid substitutions for all whBh were found in these genes. In contrast, a genome region containing six coding sequences (CDSs) had consistent nucleotide sequence differences between strongly and whBh isolates. Two CDSs were predicted to encode ABC transporter proteins, and a TolC family protein, which may have a role in the export of haemolysins from B. hyodysenteriae. Another difference in this region was the presence of three CDSs in whBh that are pseudogenes in strongly Haemolytic isolates. One of the intact CDSs from whBh encoded a predicted PadR-like transcriptional repressor that may play a role in repression of haemolysis functions. In summary, a sub-clade of whBh isolates has emerged in Europe, and several genomic differences, that potentially explain the weakly Haemolytic phenotype, were identified. These markers may provide targets for discriminatory molecular tests needed in SD surveillance.
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An avirulent Brachyspira hyodysenteriae strain elicits intestinal IgA and slows down spread of swine dysentery
Veterinary Research, 2017Co-Authors: Maxime Mahu, Stefano Canessa, Jackeline Zavala Marchan, An Martel, Filip Boyen, Freddy Haesebrouck, Frank PasmansAbstract:AbstractSwine dysentery caused by Brachyspira hyodysenteriae, results in substantial economic losses in swine producing countries worldwide. Although a number of different vaccine approaches have been explored with regard to this disease, they show limitations and none of them have reached the market. We here determine the vaccine potential of a weakly Haemolytic B. hyodysenteriae strain. The virulence of this strain was assessed in experimental infection trials and its protection against swine dysentery was quantified in a vaccination-challenge experiment using a seeder infection model. Systemic IgG production and local IgA production were monitored in serum and faeces respectively. Across all trials, pigs that were colonized by virulent, strongly Haemolytic B. hyodysenteriae strains consistently developed swine dysentery, in contrast to none of the pigs colonized by the weakly Haemolytic B. hyodysenteriae vaccine strain. In the seeder vaccination trial nearly all immunised animals developed swine dysentery on subsequent challenge with a virulent strain, but the speed of spread of swine dysentery and faecal score were significantly reduced in animals immunised with the weakly Haemolytic strain compared to sham-immunised animals. The IgA response of immunised animals upon challenge with a virulent B. hyodysenteriae strain significantly correlated to a later onset of disease. The correlation between local IgA production and protection induced by a weakly Haemolytic B. hyodysenteriae strain provides leads for future vaccine development against swine dysentery.
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non Haemolytic mannheimia Haemolytica as a cause of pleuropneumonia and septicemia in a calf
Veterinary Microbiology, 2015Co-Authors: Maxime Mahu, Bonnie Valgaeren, Bart Pardon, Piet Deprez, Freddy Haesebrouck, Filip BoyenAbstract:Pure cultures of non-Haemolytic Mannheimia Haemolytica, were cultivated from pleural effusion fluid and blood from a 1-month old Belgian Blue bull calf that was presented with apathy and anorexia. The isolates were identified as M. Haemolytica by 16S rRNA gene sequencing and MALDI-TOF-MS. Since haemolysis on blood agar plates is considered a hallmark of M. Haemolytica we wanted to elucidate the unusual phenotype of the isolated strain. Therefore the leukotoxin operon (lktCABD), responsible for the Haemolytic phenotype of M. Haemolytica and regarded as the most important virulence factor, was completely sequenced. The leukotoxin operon of the isolated strain showed a deletion in the lktA gene, resulting in a truncated LktA protein. The absence of a complete LktA protein is responsible for the non-Haemolytic phenotype of the strain. To the best of our knowledge, this is the first report of a well-characterized non-Haemolytic M. Haemolytica isolate causing disease in cattle.
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first isolation of brachyspira hampsonii from pigs in europe
Veterinary Record, 2014Co-Authors: Maxime Mahu, Frank Pasmans, Freddy Haesebrouck, E De Jong, N De Pauw, Vande L Maele, Virginie Vandenbroucke, Tamara Vandersmissen, C Miry, An MartelAbstract:Infections with Brachyspira species in swine occur in most swine-rearing countries and can result in substantial economic losses. Of all swine-related Brachyspira species Infections, classical swine dysentery, caused by Brachyspira hyodysenteriae , results in the most severe clinical symptoms (eg, mucohaemorrhagic diarrhoea, weight loss, poor feed conversion). B hyodysenteriae was first recognised as the cause of swine dysentery in 1971 (Taylor and Alexander 1971). At that time, the strong haemolysis of B hyodysenteriae appeared indicative for pathogenicity since other, weakly Haemolytic Brachyspira (formerly Serpulina , Serpula and Treponema ) appeared to be commensal, and were therefore named Brachyspira innocens (Kinyon and Harris 1979). Several reports of clinical disease caused by weakly Haemolytic Brachyspira indicated that not all weakly Haemolytic Brachyspira species were non-pathogenic for pigs (Taylor and others 1980, Neef and others 1994). Further research of these weakly Haemolytic isolates including DNA-DNA hybridisation, resulted in the designation of three more weakly Haemolytic species, namely Brachyspira intermedia , Brachyspira murdochii and Brachyspira pilosicoli (Trott and others 1996, Stanton and others 1997). These weakly Haemolytic species of Brachyspira diverge in the severity of clinical symptoms they cause. B pilosicoli is pathogenic and causes spirochetal colitis in pigs, which is marked by non-haemorrhagic diarrhoea and a poor feed conversion. For B intermedia and B murdochii , the pathogenic potential is less clear-cut. Although both species have been isolated from clinical cases of diarrhoea, the clinical symptoms are mild or absent in experimental infections, and yet, high numbers of spirochetes are necessary to cause an effect (Jensen and others 2004, Jensen and others 2010). Recently, a new type of Brachyspira infection has been described. Outbreaks of mucohaemorrhagic diarrhoea, caused by strongly Haemolytic Brachyspira strains inconsistent with B hyodysenteriae , were reported in the USA and Canada. Phylogenetic analysis of these strains …
David J. Hampson - One of the best experts on this subject based on the ideXlab platform.
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An atypical weakly Haemolytic strain of Brachyspira hyodysenteriae is avirulent and can be used to protect pigs from developing swine dysentery
Veterinary research, 2019Co-Authors: Nyree D. Phillips, Flaminia Coiacetto, David J. HampsonAbstract:The anaerobic intestinal spirochaete Brachyspira hyodysenteriae colonises the large intestine of pigs and causes swine dysentery (SD), a severe mucohaemorrhagic colitis. SD occurs worldwide, and control is hampered by a lack of vaccines and increasing antimicrobial resistance. B. hyodysenteriae strains typically produce strong beta-haemolysis on blood agar, and the Haemolytic activity is thought to contribute to the pathogenesis of SD. Recently, weakly Haemolytic variants of B. hyodysenteriae have been identified in Europe and Australia, and weakly Haemolytic strain D28 from Belgium failed to cause disease when used experimentally to infect pigs. Moreover, pigs colonised with D28 and then challenged with virulent strongly Haemolytic strain B204 showed a delay of 2–4 days in developing SD compared to pigs not exposed to D28. The current study aimed to determine whether Australian weakly Haemolytic B. hyodysenteriae strain MU1, which is genetically distinct from D28, could cause disease and whether exposure to it protected pigs from subsequent challenge with strongly Haemolytic virulent strains. Three experimental infection studies were undertaken in which no diseases occurred in 34 pigs inoculated with MU1, although mild superficial lesions were found in the colon in 2 pigs in one experiment. In two experiments, significantly fewer pigs exposed to MU1 and then challenged with strongly Haemolytic virulent strains of B. hyodysenteriae developed SD compared to control pigs not previously exposed to MU1 (p = 0.009 and p = 0.0006). These data indicate that MU1 lacks virulence and has potential to be used to help protect pigs from SD.
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Weakly Haemolytic variants of Brachyspira hyodysenteriae newly emerged in Europe belong to a distinct subclade with unique genetic properties
Veterinary Research, 2019Co-Authors: Roderick M. Card, Maxime Mahu, Nyree D. Phillips, David J. Hampson, Eric R. Burrough, Richard J. Ellis, Javier Nunez-garcia, Jill R. Thomson, Judith Rohde, Alexander W. TuckerAbstract:Brachyspira ( B. ) hyodysenteriae is widespread globally, and can cause mucohaemorrhagic colitis (swine dysentery, SD) with severe economic impact in infected herds. Typical strains of B. hyodysenteriae are strongly Haemolytic on blood agar, and the Haemolytic activity is believed to contribute to virulence in vivo. However, recently there have been reports of atypical weakly Haemolytic isolates of B. hyodysenteriae (whBh). In this study, 34 European whBh and 82 strongly Haemolytic isolates were subjected to comparative genomic analysis. A phylogenetic tree constructed using core single nucleotide polymorphisms showed that the whBh formed a distinct sub-clade. All eight genes previously associated with haemolysis in B. hyodysenteriae were present in the whBh. No consistent patterns of amino acid substitutions for all whBh were found in these genes. In contrast, a genome region containing six coding sequences (CDSs) had consistent nucleotide sequence differences between strongly and whBh isolates. Two CDSs were predicted to encode ABC transporter proteins, and a TolC family protein, which may have a role in the export of haemolysins from B. hyodysenteriae. Another difference in this region was the presence of three CDSs in whBh that are pseudogenes in strongly Haemolytic isolates. One of the intact CDSs from whBh encoded a predicted PadR-like transcriptional repressor that may play a role in repression of haemolysis functions. In summary, a sub-clade of whBh isolates has emerged in Europe, and several genomic differences, that potentially explain the weakly Haemolytic phenotype, were identified. These markers may provide targets for discriminatory molecular tests needed in SD surveillance.
Subramaniam Srikumaran - One of the best experts on this subject based on the ideXlab platform.
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β-Hemolysis May Not Be a Reliable Indicator of Leukotoxicity of Mannheimia Haemolytica Isolates
MDPI AG, 2018Co-Authors: Jegarubee Bavananthasivam, Sudarvili Shanthalingam, Abirami Kugadas, Bindu Raghavan, Sai Batra, Subramaniam SrikumaranAbstract:Mannheimia (Pasteurella) Haemolytica causes bronchopneumonia in domestic and wild ruminants. Leukotoxin is the critical virulence factor of M. Haemolytica. Since β-hemolysis is caused by a large number of leukotoxin-positive M. Haemolytica isolates, all β-hemolytic M. Haemolytica isolates are considered to be leukotoxic as well. However, conflicting reports exist in literature as to the leukotoxic and hemolytic properties of M. Haemolytica. One group of researchers reported their leukotoxin-deletion mutants to be hemolytic while another reported their mutants to be non-hemolytic. The objective of this study was to determine whether β-hemolysis is a reliable indicator of leukotoxicity of M. Haemolytica isolates. Ninety-five isolates of M. Haemolytica were first confirmed for presence of leukotoxin gene (lktA) by a leukotoxin-specific PCR assay. Culture supernatant fluids from these isolates were then tested for presence of leukotoxin protein by an ELISA, and for leukotoxic activity by a cytotoxicity assay. All isolates were tested for β-hemolysis by culture on blood agar plates. Sixty-two isolates (65%) produced leukotoxin protein while 33 isolates (35%) did not. Surprisingly, 18 of the 33 isolates (55%), that did not produce leukotoxin protein, were hemolytic. Of the 62 isolates that produced leukotoxin, 55 (89%) were leukotoxic while 7 (11%) were not. All except one of the 55 leukotoxic isolates (98%) were also hemolytic. All seven isolates that were not leukotoxic were hemolytic. Taken together, these results suggest that β-hemolysis may not be a reliable indicator of leukotoxicity of M. Haemolytica isolates. Furthermore, all M. Haemolytica isolates that possess lktA gene may not secrete active leukotoxin
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sequence diversity cytotoxicity and antigenic similarities of the leukotoxin of isolates of mannheimia species from mastitis in domestic sheep
Veterinary Microbiology, 2014Co-Authors: Lida Omaleki, Subramaniam Srikumaran, Glenn F Browning, Stuart R Barber, Joanne L Allen, Philip F MarkhamAbstract:Species within the genus Mannheimia are among the most important causes of ovine mastitis. Isolates of these species can express leukotoxin A (LktA), a primary virulence factor of these bacteria. To examine the significance of variation in the LktA, the sequences of the lktA genes in a panel of isolates from cases of ovine mastitis were compared. The cross-neutralising capacities of rat antisera raised against LktA of one Mannheimia glucosida, one Haemolytic Mannheimia ruminalis, and two Mannheimia Haemolytica isolates were also examined to assess the effect that variation in the lktA gene can have on protective immunity against leukotoxins with differing sequences. The lktA nucleotide distance between the M. Haemolytica isolates was greater than between the M. glucosida isolates, with the M. Haemolytica isolates divisible into two groups based on their lktA sequences. Comparison of the topology of phylogenetic trees of 16S rDNA and lktA sequences revealed differences in the relationships between some isolates, suggesting horizontal gene transfer. Cross neutralisation data obtained with monospecific anti-LktA rat sera were used to derive antigenic similarity coefficients for LktA from the four Mannheimia species isolates. Similarity coefficients indicated that LktA of the two M. Haemolytica isolates were least similar, while LktA from M. glucosida was most similar to those for one of the M. Haemolytica isolates and the Haemolytic M. ruminalis isolate. The results suggested that vaccination with the M. glucosida leukotoxin would generate the greatest cross-protection against ovine mastitis caused by Mannheimia species with these alleles.
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growth of mannheimia Haemolytica inhibitory agents and putative mechanism of inhibition
Veterinary Microbiology, 2014Co-Authors: Abirami Kugadas, Jegarubee Bavananthasivam, Douglas R Call, Jessica Poindexter, Kelly A Brayton, Subramaniam SrikumaranAbstract:Abstract Leukotoxin-producing Mannheimia Haemolytica consistently causes fatal pneumonia in bighorn sheep (BHS) under experimental conditions. Surprisingly, by culture methods, it has been isolated from pneumonic BHS lungs less frequently than other bacteria. However, in one study PCR assays detected M. Haemolytica from over 70% of the pneumonic lung samples that were negative for this organism by culture, suggesting that the growth of M. Haemolytica is inhibited by other bacteria. Previously, we have shown that Bibersteinia trehalosi inhibits the growth of M. Haemolytica . Herein we report that 100% of a diverse panel of B. trehalosi isolates ( n = 55) tested in a bacterial competition assay inhibited the growth of M. Haemolytica , suggesting that the inhibitory phenotype is conserved. Further, no plasmids were isolated from any of the 30 B. trehalosi isolates tested, suggesting that the effectors are chromosomally encoded. An earlier study by us showed that Pasteurella multocida also inhibits the growth of M. Haemolytica. However, M. Haemolytica has not been isolated even from pneumonic BHS lungs that did not carry B. trehalosi or P. multocida . Consequently, we tested Staphylococcus spp., Streptococcus spp., and Escherichia coli , the bacteria that have been detected frequently in pneumonic BHS lungs, for possible inhibition of M. Haemolytica . Neither the Staphylococcus spp. nor the Streptococcus sp. strains inhibited the growth of M. Haemolytica . E. coli inhibited the growth of M. Haemolytica by a proximity-dependent mechanism. Growth inhibition of M. Haemolytica by several bacterial species is likely to contribute to the infrequent detection of this bacterium from pneumonic BHS lungs by culture.
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proximity dependent inhibition of growth of mannheimia Haemolytica by pasteurella multocida
Applied and Environmental Microbiology, 2012Co-Authors: Jegarubee Bavananthasivam, Sudarvili Shanthalingam, Abirami Kugadas, Rohana P Dassanayake, Douglas R Call, Donald P Knowles, Subramaniam SrikumaranAbstract:ABSTRACT Mannheimia Haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. Haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. Haemolytica has been isolated by culture less frequently than the other bacteria. We hypothesized that the growth of M. Haemolytica is inhibited by other bacteria in the lungs of BHS. The objective of this study was to determine whether P. multocida inhibits the growth of M. Haemolytica. Although in monoculture both bacteria exhibited similar growth characteristics, in coculture with P. multocida there was a clear inhibition of growth of M. Haemolytica. The inhibition was detected at mid-log phase and continued through the stationary phase. When cultured in the same medium, the growth of M. Haemolytica was inhibited when both bacteria were separated by a membrane that allowed contact (pore size, 8.0 μm) but not when they were separated by a membrane that limited contact (pore size, 0.4 μm). Lytic bacteriophages or bactericidal compounds could not be detected in the culture supernatant fluid from monocultures of P. multocida or from P. multocida-M. Haemolytica cocultures. These results indicate that P. multocida inhibits the growth of M. Haemolytica by a contact- or proximity-dependent mechanism. If the inhibition of growth of M. Haemolytica by P. multocida occurs in vivo as well, it could explain the inconsistent isolation of M. Haemolytica from the lungs of pneumonic BHS.
Nyree D. Phillips - One of the best experts on this subject based on the ideXlab platform.
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An atypical weakly Haemolytic strain of Brachyspira hyodysenteriae is avirulent and can be used to protect pigs from developing swine dysentery
Veterinary research, 2019Co-Authors: Nyree D. Phillips, Flaminia Coiacetto, David J. HampsonAbstract:The anaerobic intestinal spirochaete Brachyspira hyodysenteriae colonises the large intestine of pigs and causes swine dysentery (SD), a severe mucohaemorrhagic colitis. SD occurs worldwide, and control is hampered by a lack of vaccines and increasing antimicrobial resistance. B. hyodysenteriae strains typically produce strong beta-haemolysis on blood agar, and the Haemolytic activity is thought to contribute to the pathogenesis of SD. Recently, weakly Haemolytic variants of B. hyodysenteriae have been identified in Europe and Australia, and weakly Haemolytic strain D28 from Belgium failed to cause disease when used experimentally to infect pigs. Moreover, pigs colonised with D28 and then challenged with virulent strongly Haemolytic strain B204 showed a delay of 2–4 days in developing SD compared to pigs not exposed to D28. The current study aimed to determine whether Australian weakly Haemolytic B. hyodysenteriae strain MU1, which is genetically distinct from D28, could cause disease and whether exposure to it protected pigs from subsequent challenge with strongly Haemolytic virulent strains. Three experimental infection studies were undertaken in which no diseases occurred in 34 pigs inoculated with MU1, although mild superficial lesions were found in the colon in 2 pigs in one experiment. In two experiments, significantly fewer pigs exposed to MU1 and then challenged with strongly Haemolytic virulent strains of B. hyodysenteriae developed SD compared to control pigs not previously exposed to MU1 (p = 0.009 and p = 0.0006). These data indicate that MU1 lacks virulence and has potential to be used to help protect pigs from SD.
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Weakly Haemolytic variants of Brachyspira hyodysenteriae newly emerged in Europe belong to a distinct subclade with unique genetic properties
Veterinary Research, 2019Co-Authors: Roderick M. Card, Maxime Mahu, Nyree D. Phillips, David J. Hampson, Eric R. Burrough, Richard J. Ellis, Javier Nunez-garcia, Jill R. Thomson, Judith Rohde, Alexander W. TuckerAbstract:Brachyspira ( B. ) hyodysenteriae is widespread globally, and can cause mucohaemorrhagic colitis (swine dysentery, SD) with severe economic impact in infected herds. Typical strains of B. hyodysenteriae are strongly Haemolytic on blood agar, and the Haemolytic activity is believed to contribute to virulence in vivo. However, recently there have been reports of atypical weakly Haemolytic isolates of B. hyodysenteriae (whBh). In this study, 34 European whBh and 82 strongly Haemolytic isolates were subjected to comparative genomic analysis. A phylogenetic tree constructed using core single nucleotide polymorphisms showed that the whBh formed a distinct sub-clade. All eight genes previously associated with haemolysis in B. hyodysenteriae were present in the whBh. No consistent patterns of amino acid substitutions for all whBh were found in these genes. In contrast, a genome region containing six coding sequences (CDSs) had consistent nucleotide sequence differences between strongly and whBh isolates. Two CDSs were predicted to encode ABC transporter proteins, and a TolC family protein, which may have a role in the export of haemolysins from B. hyodysenteriae. Another difference in this region was the presence of three CDSs in whBh that are pseudogenes in strongly Haemolytic isolates. One of the intact CDSs from whBh encoded a predicted PadR-like transcriptional repressor that may play a role in repression of haemolysis functions. In summary, a sub-clade of whBh isolates has emerged in Europe, and several genomic differences, that potentially explain the weakly Haemolytic phenotype, were identified. These markers may provide targets for discriminatory molecular tests needed in SD surveillance.
