Histophilus somni

Last updated

Histophilus somni
Scientific classification
Domain:
Phylum:
Class:
Order:
Family:
Genus:
Histophilus

Angen et al. 2003
Species

Histophilus somni

Synonyms [1]
  • Haemophilus somnus
  • Histophilus ovis
  • Histophilus agni

Histophilus somni is a non-motile, gram-negative, rod or coccobacillus shaped, facultative anaerobe bacterial species belonging to the family Pasteurellaceae. [2] Prior to 2003, it was thought Haemophilus somnus, Histophilus ovis, and Histophilus agni were three different species, but now are all classified as Histophilus somni. Histophilus somni is a commensal bacteria of mucous membranes of the upper respiratory tract and reproductive tract [3] [4] [5] [6] with a global prevalence [6] and is found in cattle and other small ruminants. [4] Histophilus somni is also a known causative agent that is a part of the Bovine Respiratory Disease (BRD) complex, [4] which typically involves multiple pathogens residing together in biofilm environments. Histophilus somni may also cause Histophilosus symptoms and clinical presentation will depend on the tissue affected. [5] When disease does occur, it can be difficult to catch in time and is often diagnosed post mortem. [7] This means that treatment often involves metaphylactic mass treatment or no treatment at all. This organism is more fastidious than others and requires knowledge for sample collection, storage and culture. Genomic studies related to this bacteria have enabled scientists to pinpoint antibiotic resistance genes.   

Contents

Description

Histophilus somni is a member of the Pasteurellaceae family [8] and was first isolated from cattle in 1956. [9] Histophilus somni is a gram-negative, rod or coccobacillus shaped bacteria that does not express pili or flagella making it non-motile. [8] Many species of the Pasteurellaceae family are encapsulated; however, based on electron microscopy and ruthenium red staining results H. somni is not encapsulated. [10]

Prior to 2003 Histophilus somni was considered to be three different species Haemophilus somnus, Histophilus ovis, and Histophilus agni. [11] [12] Histophilus somni is a normal part of mucosal microflora in the upper respiratory and genital tract of bovine and ovine animals, yet, under the right conditions is one of multiple bacteria responsible for causing bovine respiratory disease. [13] Under normal conditions BRD complex bacteria symbiotically reside together in biofilm environments. [14] The biofilm protects H. somni from harmful substances while allowing co-existence with the host by down regulating virulence factor productions. [14] Although H. Somni is known to survive the harsh intracellular environments of host phagocytic cells, [15] the bacteria is considered fragile in the external environment and does not survive well outside of the host.

Culture and Biochemistry

Culture and Identification

Histophilus is a fastidious bacterium and has some special requirements for culturing. A differentiating factor between Histophilus somni and the Haemophilus species is that Histophilus species are able to grow in the absence of Factor X (heat stable hemin) and Factor V (NAD) although their growth is increased in the presence of these factors. [11] [16] Histophilus grows best on chocolate agar at 37 °C with 5-10% CO2 and is unable to grow on MacConkey agar. [11] Cultures have been developed in hopes to make culturing Histophilus easier, but trials are usually unsuccessful. Histophilus can be grown in Columbia broth or brain heart infusion broth with the supplementation of thiamine monophosphate. [8] Culturing in a broth before plate culturing will help isolate Histophilus from other commensal bacteria at the sample site. [8] The colonies are quite small and usually only reach a size of 1-2mm. [17] When grown on blood agar, Histophilus will have a clear areas around the colonies. [8] The dew-drop shaped colonies grown on chocolate agar are tinged yellow which is a distinguishing factor of these colonies. [11]

Because Histophilus is fragile outside the host, care must be taken when collecting samples for laboratory diagnosis. Samples can try out very easily and should be cultured as soon as possible. The best storage method for samples to stay viable is for deep freezing below -60 degrees Celsius. [11]

The best way to identify H. somni is through 16S rDNA PCR amplification. [17] [11] Microagglutination assays have been developed for identification in cattle however many animals have positive cross-reactive antibodies without having had the infection. [18] Methods have been developed for the differentiation between ovine and bovine strains of H. somni, including restriction enzyme analysis. Microscopy can be used for identification when bacteria are stained with fluorescent antibody stain. [11]

Biochemistry

Histophilus species can be difficult to identify with biochemical reactions as many of the tests used for identification do not have consistent results. Tests consistent throughout Histophilus colonies are oxidase and catalase tests, with oxidase having positive results and catalase being negative. [19] [16] Histophilus does not exhibit consistent hemolysis. [11] Their ability to reduce nitrogen allows them to be facultative anaerobes and their growth on culture will increase with an increased atmospheric CO2. Histophilus has the ability to ferment glucose, has variable results with lactose and mannitol and are unable to ferment sucrose. [11] Antimicrobial testing has demonstrated that H. somni is still susceptible to most antimicrobials, though some strains have shown resistance to tetracycline. [8]

Biochemical TestResult
CatalaseNegative
OxidasePositive
HemolysisVariable
IndoleVariable
GlucosePositive
Nitrate reductionPositive
SucroseNegative
LactoseVariable
MannitolVariable

Genetics

In 1995 Haemophilus influenzae was genetically sequenced, a close relative to Histophilus somni and the first free living organism to have its complete genome sequenced. [12] Due to the economic importance from production losses the genomes of both Histophilus somni pneumonia strain 2336 (2,263,857 base pairs with 1,980 protein coding genes) and preputial strain 129Pt (2,007,700 base pairs with 1,792 protein coding genes) have since been sequenced. [12] [20] The genome studies of Histophilus somni strains have identified specific markers encoding tetracycline resistance, and virulence factors, while allowing a better understanding of the role of horizontal gene transfer in the evolution of these strains [12] Plasmid-borne antimicrobial resistance is an important topic in modern microbiology and occurs commonly in members of the Pasteurellaceae family. [12] Histophilus somni with tetracycline resistant plasmids have been cultured from nasal swabs of calves. [12] Using plasmid profiling as a way to identify isolated Histophilus somni from field samples gives veterinarians the ability to practice antimicrobial stewardship and reduce the impact of antimicrobial resistance.

Pathogenesis and Virulence

Histophilus somni can be characterized as an opportunistic pathogen and successful disease can be established because of poor environmental factors and the bacteria's own virulence factors. [6] H. somni has numerous virulence factors including surface proteins, binding to and induction of apoptosis in host endothelial cells, immunoglobulin binding proteins, phase variation, endotoxin, biofilm formation, free radical inhibition, and survival of phagocytosis that allow the bacteria to colonize host tissues and evade the host's immune system. [6] [18] [21] [22] Depending on the strain of H. somni, not all of the listed virulence factors may be present. [23]

Due to the role of H. somni as a commensal bacterium in the respiratory tract, an important part of establishing disease lies in the relationship between respiratory epithelial cells and the bacterium. [21] It has been suggested that pathogenesis begins when the bacteria invades and crosses the pulmonary alveolar membrane or that it can cause both bovine turbinate (BT) and bovine alveolar type 2 (BAT2) cells to retract allowing passage of the bacteria into the bloodstream. [21] In order successfully cross into the blood, in addition to causing respiratory endothelium cells to retract, H. somni disrupts the basement membrane via digestion by increasing production of metalloproteinases from BAT2 cells. [21] After entry into the bloodstream, the bacteria can colonize other tissues around the body such as the heart and is involved in biofilm production on cardiac endothelium in bovine myocarditis. [21]

H. somni surface proteins have been studied in association to virulence and pathogenesis. In serum resistant virulent strains, outer membrane proteins such as a sialic acid-modified lipooligosaccharide (LOS) and immunoglobulin-binding protein-A (IbpA) were found to be important . [21] [22] [23] H. somni LOS provides critical protection to the bacterium against host defences by undergoing phase variation both structurally and antigenically and acts as an endotoxin producing apoptotic activity in bovine epithelial cells, a classical sign of histophilosis. [22] [23] Upper respiratory tract colonization is possible through decoration of LOS with phase-variable phosphorycholine (ChoP) that binds to host cell platelet-activating factor receptors allowing H. somni to colonize host tissues while evading the immune response. [22] [23] H. somni immunoglobulin-binding proteins have two repeat domains (DR1 and DR2) that have cytotoxic Fic motifs as well as an ability to bind to bovine IgG2. [21] IbpA DR2 can be taken up by BAT2 cells via pinocytosis and decreasing its cytotoxicity. [21] DR1 and DR2 Fic motifs aid in cell infection by transmigration by causing retraction of respiratory cells. [21]

H. somni has the ability to produce a branching, mannose-galactose biofilm made primarily of polysaccharide. [24] As previously mentioned, the bacteria is capable of producing biofilm in the heart of affected animals with clinical bovine myocarditis. [21] Evidence suggests that biofilm formation allows H. somni to remain protected and persist within the host. [24]

Another way that H. somni can evade the host immune system is by preventing intracellular killing. [22] Although the mechanism is unknown, the bacteria is able to reduce the amount of reactive oxygen intermediates (ROIs) and therefore the oxidative burst from bovine polymorphonuclear cells (PMNs) reducing intracellular killing. [22] In calves infected with H. somni it has been shown that phagocytosis of the bacteria is reduced in comparison to naive calves. [22]

Disease

The general term for diseases caused by Histophilus somni is called Histophilosis; [4] [12] [5] [7] Disease mainly affects cattle but can affect other small ruminants, sheep, bighorn sheep, and bison. [6] [18] [7] [12] Castration and weaning predispose young animals to disease caused by Histophilus somni. [18] [5] Other stressors such as overcrowding, poor weather, or shipping [6] are other predisposing factors for all cattle. Viral infections are another predisposing factor for all cattle. [25] [4] [7] [18] With predisposing factors in mind, there are still many unknowns in regards to how and where Histophilus somni is first able to establish infection. [7] Histophilosis may be present as a component of the Bovine Respiratory Disease Complex [4] [5] [7] [18] which has a higher incidence in feedlot cattle. [7] Histophilosis may also present as septucemia, [5] thrombotic meningoencephalitis-myelitis, [7] pneumonia, pleuritis, pericarditis, necrotizing myocarditis, and arthritis. [12] Clinical signs of Histophilosis may include central nervous system signs such as depression, behavioral changes, and ataxia, respiratory signs, abortion, conjunctivitis, fever, poor body condition, anorexia, and exercise intolerance but in general clinical signs will depend on which body tissues are affected. [12] [4] [5] [7] Histophilosis may present acutely with sudden death, [12] [5] [7] but may also present only upon post mortem examination with lesions that may be found in multiple locations in the body including the pleura, lung tissue, myocardium, joints, retina, and reproductive tissues. [12] [4] [5] [6] [7] Damage to these areas are caused by thrombus formation and thromboemboli in a septucemic animal followed by subsequent infarction and necrosis of tissue. [5] [7]

Diagnosis and Treatment

Diagnosis of Histophilus somni infection is difficult to do because the range of disease can be broad and vague. Clinicians can try to diagnose in herds using a microagglutination test but this also proves difficult because clinically healthy herds might have high antibody titers, there are many cross reactive antibodies, there are conflicting effects due to herd vaccination and there is asymptomatic colonization at mucosal sites. [7] Histophilosis is often diagnosed on post mortem examination of cattle and gross lesion include pinpoint bloody lesions called petechia, larger areas of hemorrhage called ecchymoses and necrosis in the brain, vasculitis caused by endothelial damage and more. [26] H. somni can be a part of the bovine respiratory disease (BRD) and causes pneumonia and has been detected in up to 40% of lungs with pneumonia. [27] When H. somni is detected in pneumonic lungs, it presents as fibrinosuppurative bronchopneumonia and/or severe, diffuse fibrinous pleuritis. [27] Diagnosis can be made by testing blood, cerebrospinal fluids, joint or pleural fluids for bacterial DNA via PCR or bacterial culture techniques. [7] [26] Although it is difficult to diagnose H. somni in herds, it is important to attempt it because bovine r disease is a production limiting disease and is reportable for domestic and international trade. [28]

Typically there are three approaches to dealing with Histophilus somni in a herd of cattle; mass antibiotic treatment, H. somni vaccination or vaccination for other pathogens that are known to be a part of the BRD. [7] [27] These are not treatment per se, more methods of control or metaphylactic treatment, as we are treating many animals before there is an actual diagnosis. [7] The goal is to reduce the onset of BRD or other clinical presentations of H. somni infections.  

Like other bacterial infections, antibiotic susceptibility assays should be performed and it has been reported that Hisotphilus somni is usually susceptible to ceftiofur, penicillin, enrofloxacin, florfenicol, and tetracycline. [7] This is troublesome because we know that it is difficult to diagnose before a post mortem is completed and there is no point in treating a deceased animal. Therefore, producers often treat metaphylactically, or on suspicion of infection. Tilmicosin can be added to the feed and has been shown to reduce the levels of H. somni in herds. [29] It should only be added to the feed for 14 days, should be used sparingly as resistance is likely to occur otherwise, producers should be aware of withdrawal times. [29] Problems with antibiotic treatment is emerging resistance to tetracyclines, enrofloxacin, and florfenicol. [27] Biofilms that are formed by H. somni function to protect the bacteria from host immune defenses, they also provide a barrier that impedes antibiotic function. [30] A new line of research is treating susceptible populations with bacterial isolates from subclinical carriers of Histophilus somni to act like a probiotic bacteria for the respiratory tract. A nasal inoculation of a nonpathogenic strain of H. somni could allow for the respiratory tract mucosa to be colonized with the commensal bacteria. [27]

There are many licensed vaccines against H. somni, however licensed does not mean effective. [7] [27] [28] [30] There is a push to develop new vaccines that are multi-pathogenic and DIVA compatible. [28] H. somni vaccines are usually killed cells or specific outer membrane proteins but have not been proven to be effective at protecting cattle against disease. [27] There are many constraints to vaccine use on top of ineffectiveness, including the timeliness of administration, adverse reactions from individuals in the herd, and research into the epidemiology of the disease. [7] [28] In order to treat this infection, one must know which organ system it is affecting and some systems, such as the neurological presentation does not allow for timely treatment because by the time the disease is detected, it is too late for treatment. [26]

Related Research Articles

<i>Staphylococcus aureus</i> Species of Gram-positive bacterium

Staphylococcus aureus is a gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe, meaning that it can grow without oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA). The bacterium is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.

Virulence is a pathogen's or microorganism's ability to cause damage to a host.

<i>Streptococcus pneumoniae</i> Species of bacterium

Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic member of the genus Streptococcus. S. pneumoniae cells are usually found in pairs (diplococci) and do not form spores and are non motile. As a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies.

<i>Haemophilus influenzae</i> Species of bacterium

Haemophilus influenzae is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacteria are mesophilic and grow best at temperatures between 35 and 37 °C.

<i>Vibrio parahaemolyticus</i> Species of bacterium

Vibrio parahaemolyticus (V. parahaemolyticus) is a curved, rod-shaped, Gram-negative bacterial species found in the sea and in estuaries which, when ingested, may cause gastrointestinal illness in humans. V. parahaemolyticus is oxidase positive, facultatively aerobic, and does not form spores. Like other members of the genus Vibrio, this species is motile, with a single, polar flagellum.

<i>Neisseria meningitidis</i> Species of bacterium that can cause meningitis

Neisseria meningitidis, often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a coccus because it is round, and more specifically a diplococcus because of its tendency to form pairs.

<i>Pseudomonas aeruginosa</i> Species of bacterium

Pseudomonas aeruginosa is a common encapsulated, Gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. P. aeruginosa is able to selectively inhibit various antibiotics from penetrating its outer membrane - and has high resistance to several antibiotics. According to the World Health Organization P. aeruginosa poses one of the greatest threats to humans in terms of antibiotic resistance.

<i>Moraxella catarrhalis</i> Species of bacterium

Moraxella catarrhalis is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the infection of the host cell by sticking to the host cell using trimeric autotransporter adhesins.

Bovine alphaherpesvirus 1 (BoHV-1) is a virus of the family Herpesviridae and the subfamily Alphaherpesvirinae, known to cause several diseases worldwide in cattle, including rhinotracheitis, vaginitis, balanoposthitis, abortion, conjunctivitis, and enteritis. BoHV-1 is also a contributing factor in shipping fever, also known as bovine respiratory disease (BRD). It is spread horizontally through sexual contact, artificial insemination, and aerosol transmission and it may also be transmitted vertically across the placenta. BoHV-1 can cause both clinical and subclinical infections, depending on the virulence of the strain. Although these symptoms are mainly non-life-threatening it is an economically important disease as infection may cause a drop in production and affect trade restrictions. Like other herpesviruses, BoHV-1 causes a lifelong latent infection and sporadic shedding of the virus. The sciatic nerve and trigeminal nerve are the sites of latency. A reactivated latent carrier is normally the source of infection in a herd. The clinical signs displayed are dependent on the virulence of the strain. There is a vaccine available which reduces the severity and incidence of disease. Some countries in Europe have successfully eradicated the disease by applying a strict culling policy.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

<i>Burkholderia cenocepacia</i> Species of bacterium

Burkholderia cenocepacia is a Gram-negative, rod-shaped bacterium that is commonly found in soil and water environments and may also be associated with plants and animals, particularly as a human pathogen. It is one of over 20 species in the Burkholderia cepacia complex (Bcc) and is notable due to its virulence factors and inherent antibiotic resistance that render it a prominent opportunistic pathogen responsible for life-threatening, nosocomial infections in immunocompromised patients, such as those with cystic fibrosis or chronic granulomatous disease. The quorum sensing systems CepIR and CciIR regulate the formation of biofilms and the expression of virulence factors such as siderophores and proteases. Burkholderia cenocepacia may also cause disease in plants, such as in onions and bananas. Additionally, some strains serve as plant growth-promoting rhizobacteria.

<i>Pasteurella multocida</i> Species of bacterium

Pasteurella multocida is a Gram-negative, nonmotile, penicillin-sensitive coccobacillus of the family Pasteurellaceae. Strains of the species are currently classified into five serogroups based on capsular composition and 16 somatic serovars (1–16). P. multocida is the cause of a range of diseases in mammals and birds, including fowl cholera in poultry, atrophic rhinitis in pigs, and bovine hemorrhagic septicemia in cattle and buffalo. It can also cause a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets. Many mammals and birds harbor it as part of their normal respiratory microbiota.

<span class="mw-page-title-main">Medical microbiology</span> Branch of medical science

Medical microbiology, the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases. In addition, this field of science studies various clinical applications of microbes for the improvement of health. There are four kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.

Porphyromonas gingivalis belongs to the phylum Bacteroidota and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.

Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobe, nonmotile bacterium that is often found in association with localized aggressive periodontitis, a severe infection of the periodontium. It is also suspected to be involved in chronic periodontitis. Less frequently, A. actinomycetemcomitans is associated with nonoral infections such as endocarditis. Its role in aggressive periodontitis was first discovered by Danish-born periodontist Jørgen Slots, a professor of dentistry and microbiology at the University of Southern California School of Dentistry.

<span class="mw-page-title-main">Pradofloxacin</span> Chemical compound

Pradofloxacin, sold under the brand name Veraflox among others, is a third-generation enhanced spectrum veterinary antibiotic of the fluoroquinolone class. It was developed by Elanco Animal Health GmbH and received approval from the European Commission in April 2011, for prescription-only use in veterinary medicine for the treatment of bacterial infections in dogs and cats.

<i>Streptococcus dysgalactiae</i> Species of bacterium

Streptococcus dysgalactiae is a gram positive, beta-haemolytic, coccal bacterium belonging to the family Streptococcaceae. It is capable of infecting both humans and animals, but is most frequently encountered as a commensal of the alimentary tract, genital tract, or less commonly, as a part of the skin flora. The clinical manifestations in human disease range from superficial skin-infections and tonsillitis, to severe necrotising fasciitis and bacteraemia. The incidence of invasive disease has been reported to be rising. Several different animal species are susceptible to infection by S. dysgalactiae, but bovine mastitis and infectious arthritis in lambs have been most frequently reported.

In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Staphylococcus pseudintermedius is a gram-positive spherically shaped bacterium of the genus Staphylococcus found worldwide. It is primarily a pathogen for domestic animals, but has been known to affect humans as well. S. pseudintermedius is an opportunistic pathogen that secretes immune-modulating virulence factors, has many adhesion factors, and the potential to create biofilms, all of which help to determine the pathogenicity of the bacterium. Diagnoses of S. pseudintermedius have traditionally been made using cytology, plating, and biochemical tests. More recently, molecular technologies like MALDI-TOF, DNA hybridization and PCR have become preferred over biochemical tests for their more rapid and accurate identifications. This includes the identification and diagnosis of antibiotic resistant strains.

Bovine respiratory disease (BRD) is the most common and costly infectious disease affecting beef cattle in the world. It is a complex, bacterial or viral infection that causes pneumonia in calves which can be fatal. The infection is usually a sum of three codependent factors: stress, an underlying viral infection, and a new bacterial infection. The diagnosis of the disease is complex since there are multiple possible causes.

References

  1. Markey, Bryan; Leonard, Finola; Archambault, Marie; Cullinane, Ann; Maguire, Dores (2013). "Chapter 26. Haemophilus and Histophilus species". Clinical Veterinary Microbiology (2nd ed.). Elsevier. p. 349. ISBN   9780702055881.
  2. Markey, Bryan K. (2013). Clinical veterinary microbiology. Elsevier. ISBN   9780702055881. OCLC   818985683.
  3. Grissett, G.P.; White, B.J.; Larson, R.L. (2015). "Structured Literature Review of Responses of Cattle to Viral and Bacterial Pathogens Causing Bovine Respiratory Disease Complex". Journal of Veterinary Internal Medicine. 29 (3): 770–780. doi:10.1111/jvim.12597. PMC   4895424 . PMID   25929158.
  4. 1 2 3 4 5 6 7 8 Baptiste, Keith Edward; Kyvsgaard, Niels Christian (2017-09-29). "Do antimicrobial mass medications work? A systematic review and meta-analysis of randomised clinical trials investigating antimicrobial prophylaxis or metaphylaxis against naturally occurring bovine respiratory disease". Pathogens and Disease. 75 (7). doi:10.1093/femspd/ftx083. ISSN   2049-632X. PMC   7108556 . PMID   28830074.
  5. 1 2 3 4 5 6 7 8 9 10 "Histophilosis - Generalized Conditions". Merck Veterinary Manual. Retrieved 2020-10-25.
  6. 1 2 3 4 5 6 7 Sandal, Indra; Inzana, Thomas J. (2010-02-01). "A genomic window into the virulence of Histophilus somni". Trends in Microbiology. 18 (2): 90–99. doi:10.1016/j.tim.2009.11.006. ISSN   0966-842X. PMID   20036125.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 O’Toole, D.; Sondgeroth, K. S. (2015), Inzana, Thomas J. (ed.), "Histophilosis as a Natural Disease", Histophilus somni, vol. 396, Cham: Springer International Publishing, pp. 15–48, doi:10.1007/82_2015_5008, ISBN   978-3-319-29554-1, PMC   7120429 , PMID   26847357
  8. 1 2 3 4 5 6 Clinical veterinary microbiology. Markey, B. K. (Bryan K.). Elsevier. 2013. ISBN   9780702055881. OCLC   818985683.{{cite book}}: CS1 maint: others (link)
  9. Corbeil, L. B.; Widders, P. R.; Gogolewski, R.; Arthur, J.; Inzana, T. J.; Ward, A. C. (1986). "Haemophilus somnus: Bovine Reproductive and Respiratory Disease". The Canadian Veterinary Journal. 27 (2): 90–93. PMC   1680186 . PMID   17422630.
  10. Sandal, Indra; Inzana, Thomas J; Molinaro, Antonio; Castro, Christina De; Shao, Jian Q; Apicella, Michael A; Cox, Andrew D; Michael, Frank St; Berg, Gretchen (2011). "Identification, structure, and characterization of an exopolysaccharide produced by Histophilus somni during biofilm formation". BMC Microbiology. 11 (1): 186. doi: 10.1186/1471-2180-11-186 . ISSN   1471-2180. PMC   3224263 . PMID   21854629.
  11. 1 2 3 4 5 6 7 8 9 Clinical veterinary microbiology. Markey, B. K. (Bryan K.) (2nd ed.). Edinburgh: Elsevier. 2013. ISBN   978-0-7234-3237-1. OCLC   818985683.{{cite book}}: CS1 maint: others (link)
  12. 1 2 3 4 5 6 7 8 9 10 11 12 Histophilus somni : biology, molecular basis of pathogenesis, and host immunity. Inzana, Thomas J. Switzerland. 11 April 2016. ISBN   978-3-319-29556-5. OCLC   946724590.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  13. Behling-Kelly, Erica; Rivera-Rivas, Jose; Czuprynski, Charles J. (2015), Inzana, Thomas J. (ed.), "Interactions of Histophilus somni with Host Cells", Histophilus somni, vol. 396, Cham: Springer International Publishing, pp. 71–87, doi:10.1007/82_2015_5010, ISBN   978-3-319-29554-1, PMID   26728064 , retrieved 2020-10-25
  14. 1 2 Mosier, Derek (2015). "Review of BRD pathogenesis: the old and the new". Animal Health Research Reviews. 15 (2): 166–168. doi:10.1017/S1466252314000176. ISSN   1466-2523. PMID   25351390. S2CID   38786230.
  15. Pan, Yu; Tagawa, Yuichi; Champion, Anna; Sandal, Indra; Inzana, Thomas J. (2018-09-10). Palmer, Guy H. (ed.). "Histophilus somni Survives in Bovine Macrophages by Interfering with Phagosome-Lysosome Fusion but Requires IbpA for Optimal Serum Resistance". Infection and Immunity. 86 (12): e00365–18, /iai/86/12/e00365–18.atom. doi:10.1128/IAI.00365-18. ISSN   0019-9567. PMC   6246896 . PMID   30201700.
  16. 1 2 "Histophilus somni". 2020-09-03.
  17. 1 2 Inzana, Thomas J. (2016). Histophilus somni; biology, molecular basis of pathogenesis and host immunity. Switzerland: Springer. pp. 2–5. ISBN   978-3-319-29554-1.
  18. 1 2 3 4 5 6 Corbeil, Lynette B. (2007). "Histophilus somni host–parasite relationships". Animal Health Research Reviews. 8 (2): 151–160. doi:10.1017/S1466252307001417. ISSN   1466-2523. PMID   18218158. S2CID   33736614.
  19. Adam Podstawka. "Histophilus somni 8025 | Type strain | DSM 23850, ATCC 43625, CCUG 36157, MCCM 00728, CIP 108133 | BacDiveID:11751". bacdive.dsmz.de. Retrieved 2020-10-26.
  20. Siddaramappa, Shivakumara; Challacombe, Jean F; Duncan, Alison J; Gillaspy, Allison F; Carson, Matthew; Gipson, Jenny; Orvis, Joshua; Zaitshik, Jeremy; Barnes, Gentry; Bruce, David; Chertkov, Olga (2011). "Horizontal gene transfer in Histophilus somni and its role in the evolution of pathogenic strain 2336, as determined by comparative genomic analyses". BMC Genomics. 12 (1): 570. doi: 10.1186/1471-2164-12-570 . ISSN   1471-2164. PMC   3339403 . PMID   22111657.
  21. 1 2 3 4 5 6 7 8 9 10 Corbeil, Lynette B. (2015), Inzana, Thomas J. (ed.), "Histophilus somni Surface Proteins", Histophilus somni, Current Topics in Microbiology and Immunology, vol. 396, Cham: Springer International Publishing, pp. 89–107, doi:10.1007/82_2015_5011, ISBN   978-3-319-29554-1, PMID   26728061 , retrieved 2020-11-02
  22. 1 2 3 4 5 6 7 Inzana, Thomas J.; Siddaramppa, Shivakumara; Inzana, Thomas J. (2004-06-01). "Haemophilus somnus virulence factors and resistance to host immunity". Animal Health Research Reviews. 5 (1): 79–93. doi:10.1079/AHR200466. PMID   15460542.
  23. 1 2 3 4 Inzana, Thomas J. (2016), Inzana, Thomas J. (ed.), "The Many Facets of Lipooligosaccharide as a Virulence Factor for Histophilus somni", Histophilus somni: Biology, Molecular Basis of Pathogenesis, and Host Immunity, Current Topics in Microbiology and Immunology, vol. 396, Cham: Springer International Publishing, pp. 131–148, doi:10.1007/82_2015_5020, ISBN   978-3-319-29556-5, PMID   26814887 , retrieved 2020-11-02
  24. 1 2 Sandal, Indra; Inzana, Thomas J.; Molinaro, Antonio; Castro, Christina De; Shao, Jian Q.; Apicella, Michael A.; Cox, Andrew D.; Michael, Frank St; Berg, Gretchen (2011-08-19). "Identification, structure, and characterization of an exopolysaccharide produced by Histophilus somniduring biofilm formation". BMC Microbiology. 11 (1): 186. doi: 10.1186/1471-2180-11-186 . ISSN   1471-2180. PMC   3224263 . PMID   21854629.
  25. Grissett, G.P.; White, B.J.; Larson, R.L. (May 2015). "Structured Literature Review of Responses of Cattle to Viral and Bacterial Pathogens Causing Bovine Respiratory Disease Complex". Journal of Veterinary Internal Medicine. 29 (3): 770–780. doi:10.1111/jvim.12597. PMC   4895424 . PMID   25929158.
  26. 1 2 3 Kessell, Ae; Finnie, Jw; Windsor, Pa (August 2011). "Neurological diseases of ruminant livestock in Australia. III: bacterial and protozoal infections: PRODUCTION ANIMALS". Australian Veterinary Journal. 89 (8): 289–296. doi:10.1111/j.1751-0813.2011.00807.x. PMID   24635630.
  27. 1 2 3 4 5 6 7 Murray, Gerard M.; O'Neill, Rónan G.; More, Simon J.; McElroy, Máire C.; Earley, Bernadette; Cassidy, Joseph P. (November 2016). "Evolving views on bovine respiratory disease: An appraisal of selected key pathogens – Part 1". The Veterinary Journal. 217: 95–102. doi:10.1016/j.tvjl.2016.09.012. PMC   7110489 . PMID   27810220.
  28. 1 2 3 4 "REPORT OF THE MEETING OF THE OIE AD HOC GROUP ON PRIORITISATION OF DISEASES FOR WHICH VACCINES COULD REDUCE ANTIMICROBIAL USE IN CATTLE, SHEEP, AND GOATS" (PDF). May 2018.
  29. 1 2 Government of Canada, Canadian Food Inspection Agency (2012-03-07). "Tilmicosin (TIL) - Medicating Ingredient Brochure". www.inspection.gc.ca. Retrieved 2020-11-05.
  30. 1 2 "Biofilm formation by Histophilus somni: The function of biofilm in bovine respiratory disease and colonization - VIRGINIA POLYTECHNIC INSTITUTE". portal.nifa.usda.gov. Retrieved 2020-11-05.