Histophilus somni IbpA Fic cytotoxin is conserved in disease strains and most carrier strains from cattle, sheep and bison

Zekarias, Bereket; O’Toole, Donal; Lehmann, Jason; Corbeil, Lynette B.

doi:10.1016/j.vetmic.2010.10.012

Cited by 13 publications

(35 citation statements)

References 27 publications

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“…Conservation of IbpA and Fic motifs in all tested H. somni disease isolates was consistent with the potential role of IbpA in disease (6). Neutralization of cytotoxicity by antibody to IbpA DR2 and protection of calves against experimental H. somni pneumonia by active immunization with recombinant IbpA DR2 confirmed its role in cytopathology and disease (6,7). Since IbpA is shed into the culture supernatant, we utilized concentrated culture supernatant (CCS) as a source of enriched crude native IbpA for studies of BRSV-H. somni synergy in breaching the alveolar barrier.…”

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confidence: 78%

“…This cytotoxicity is due to adenylylation of host cell Rho GTPases by the Fic motif (5). Conservation of IbpA and Fic motifs in all tested H. somni disease isolates was consistent with the potential role of IbpA in disease (6). Neutralization of cytotoxicity by antibody to IbpA DR2 and protection of calves against experimental H. somni pneumonia by active immunization with recombinant IbpA DR2 confirmed its role in cytopathology and disease (6,7).…”

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confidence: 68%

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Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

et al. 2013

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cOur previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSVplus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection. R espiratory infections are characteristically polymicrobial. We previously investigated the mechanisms of viral and bacterial synergy in bovine respiratory disease (BRD) (1) by infecting calves with bovine respiratory syncytial virus (BRSV) followed by infection with Histophilus somni or with either pathogen alone. The calves dually infected with BRSV and H. somni had the most severe disease and the highest serum IgE antibody responses to H. somni (1). Duration of pneumonia and persistence of H. somni in the lungs were also greatest in dually infected animals (1). Our earlier immunohistochemistry studies of experimental H. somni pneumonia showed that the bacteria are detected primarily in the alveoli at 24 h after intrabronchial inoculation (2). Since H. somni causes septicemia and its sequelae (3), it is likely that it crosses into the circulation over the alveolar barrier. We also showed that the toxic Fic (filamentation induced by cyclic AMP [cAMP]) motifs of the direct repeat domains (DR1 and DR2) of the immunoglobulin binding protein A (IbpA) cause bovine alveolar type 2 (BAT2) cells to retract in vitro, allowing paracellular migration (4). This cytotoxicity is due to adenylylation of host cell Rho GTPases by the Fic motif (5). Conservation of IbpA and Fic motifs in all tested H. somni disease isolates was c...

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confidence: 78%

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confidence: 68%

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

et al. 2013

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“…somni was found by IHC in a retrospective study of 7 of 21 bison with terminal pneumonia. A subsequent investigation found that some of the virulence factors for histophilosis in cattle, such as IbpA, are present in H. somni isolated from the palatine tonsils of healthy, commercially managed bison (Ward et al 1999a, b;Zekarias et al 2011). Pneumonia due to a complex of microorganisms is common and important in ranched bison, particularly when they are finished at feed yards.…”

Section: Bisonmentioning

confidence: 99%

Histophilosis as a Natural Disease

O’Toole

Sondgeroth

2015

Current Topics in Microbiology and Immunology

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Histophilus somni is responsible for sporadic disease worldwide in cattle and, to a lesser extent, in small ruminants, bighorn sheep (Ovis canadensis), and North American bison (Bison bison). The importance of H. somni diseases can be attributed to improved clinical and laboratory recognition, combined with the growth in intensive management practices for cattle. Although outbreaks of bovine histophilosis can occur year-round, in northern and southern hemispheres, it is most frequent in late fall and early winter. Weather, stress, dietary changes, and comingling of cattle are likely to be major triggers for outbreaks. The most frequent clinical expressions of histophilosis include undifferentiated fever, fibrinosuppurative pneumonia, encephalitis-leptomeningitis, necrotizing myocarditis, and diffuse pleuritis. Neurological disease occurs either as thrombotic meningoencephalitis (TME) or as suppurative meningitis with ventriculitis. Acute myocarditis is characteristically necrotizing and generally involves one or both papillary muscles in the left ventricular myocardium. Biofilm-like aggregates of bacteria occur in capillaries and veins in myocardium, in the central nervous system, and on endocardial surfaces. H. somni is a component of bovine respiratory disease (BRD) complex. In our experience, it is most commonly diagnosed in subacute-to-chronic polymicrobial pulmonary infections in combination with Mannheimia haemolytica, Trueperella pyogenes, Pasteurella multocida, or Mycoplasma bovis. Other, less common forms of H. somni disease present as polyarthritis/tenosynovitis, abortion with placentitis and fetal septicemia, epididymitis-orchitis, and ocular infections. It is likely that H. somni is under-recognized clinically and diagnostically. Most state and provincial laboratories in North America rely on bacterial isolation to confirm infection. The use of more sensitive detection methods on field cases of histophilosis will help resolve the pathogenesis of H. somni in natural outbreaks, and whether the disease is as common elsewhere as it is in Canada.

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“…2). The Fic domains within DR1/DR2 of IbpA have been shown to be cytotoxic to host cells (9), and the presence or absence of ibpA in all the H. somni strains used in this study has been previously documented (Table 1) (19). All the disease isolates and most of the vaginal isolatess tested were able to replicate intracellularly, but most preputial isolates tested did not (Table 1 and Fig.…”

Section: Resultsmentioning

confidence: 80%

“…2). Strains 1P, 129Pt, 130Pf, and 133P from the bovne prepuce do not produce IbpA (19) and were unable to replicate intracellularly after 24 h co-incubation (Table 1 and Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Histophilus somniSurvives in Bovine Macrophages by Interfering with Phagosome-Lysosome Fusion, but Requires IbpA for Optimal Serum Resistance

Pan

Tagawa

Champion

et al. 2018

Preprint

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20Histophilus somni survives intracellularly in professional phagocytic cells, but the 21 mechanism of intracellular survival is not understood. The Fic motif within the DR1/DR2 IbpA 22 fibrillar network protein of H. somni is cytotoxic to epithelial and phagocytic cells, which may 23 interfere with the bactericidal activity of these cells. To determine the contribution of IbpA and 24Fic on resistance to host defenses, strains and mutants that lack all of or a small region of ibpA or 25 DR1/DR2 were tested for survival in bovine monocytic cells and for serum susceptibility. A 26 mutant lacking IbpA, but not DR1/DR2, was more susceptible to killing by antiserum than the 27 parent. H. somni strains expressing IbpA replicated in bovine monocytes for at least 72 hours, 28 and were toxic for these cells. Virulent strain 2336 with transposon insertions or deletions within 29IbpA remained toxic for bovine monocytes. However, strain 2336 mutants lacking all of ibpA or 30 both DR1/DR2 were not toxic to the monocytes, but survived within the monocytes for at least 31 72 hours. Examination of intracellular trafficking of H. somni with monoclonal antibodies to 32 early and late phagosomal markers indicated that early phagosomal marker EEA-1 colocalized 33 with both disease isolate strain 2336 and serum-sensitve mucosal isolate strain 129Pt, but only 34 strain 2336 did not co-localize with late lysosomal marker LAMP-2 and prevented acidification 35 of phagosomes. These results indicate that virulent isolates of H. somni are capable of surviving 36 within phagocytic cells through interference of phagosome-lysosome maturation. Therefore, H. 37 somni may be considered a permissive intracellular pathogen. 38 3 39

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Histophilus somni IbpA Fic cytotoxin is conserved in disease strains and most carrier strains from cattle, sheep and bison

Cited by 13 publications

References 27 publications

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

Histophilosis as a Natural Disease

Histophilus somniSurvives in Bovine Macrophages by Interfering with Phagosome-Lysosome Fusion, but Requires IbpA for Optimal Serum Resistance

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